Glucose Exerts Anti-Melanogenic nyhuv Los ntawm Indirect Inactivation ntawm Tyrosinase nyob rau hauv melanocytes thiab ib tug tib neeg daim tawv nqaij sib npaug.
Mar 23, 2023
Abstract:
Qab zib yog ubiquitous nyob rau hauv cov kab mob thiab yog cov paub zoo cov khoom xyaw kom zoo nkauj rau moisturizing ntawm daim tawv nqaij nrog tsawg heev phiv. Glucose, qab zib yooj yim siv los ua lub zog los ntawm cov hlwb nyob, feem ntau yog siv rau hauv cov khoom siv tawv nqaij. Ntau cov ntawv ceeb toom tau pom tias cov suab thaj thiab cov suab thaj muaj feem xyuam nrog cov tshuaj tiv thaiv melanogenic ntawm melanocytes. Txawm li cas los xij, cov txheej txheem hauv qab molecular uas cov piam thaj inhibits melanin synthesis tsis paub, txawm tias cov piam thaj siv los ua cov tshuaj dawb thiab cov khoom siv moisturizing hauv tshuaj pleev ib ce. Ntawm no, peb pom tias cov piam thaj txo qis melanin cov ntsiab lus ntawm -melanocyte-stimulating hormone (MSH)-stimulated B16 hlwb thiab tsaus nti pigmented tib neeg melanocytes uas tsis muaj cov cim qhia ntawm cytotoxicity.
Tsis tas li ntawd, kev kho mob ntawm cov piam thaj tau pom nws qhov kev ua kom zoo nkauj los ntawm kev yees duab, Fontana-Masson (F&M) staining, thiab multi-photon microscopy hauv pigmented 3D tib neeg daim tawv nqaij qauv, MelanoDerm. Txawm li cas los xij, cov piam thaj tsis hloov pauv cov noob qhia lossis qib protein ntau ntawm cov protein ntau melanogenic hauv melanocytes. Thaum cov piam thaj txo qis hauv cov cell tyrosinase kev ua haujlwm hauv melanocytes, nws tsis txo cov nceb tyrosinase kev ua haujlwm hauv cell-free sim. Txawm li cas los xij, cov piam thaj tau metabolized rau hauv lactic acid, uas tuaj yeem ua rau muaj zog tyrosinase kev ua haujlwm. Yog li, peb tau txiav txim siab tias cov piam thaj tsis ncaj qha cuam tshuam rau kev ua haujlwm ntawm tyrosinase los ntawm kev hloov mus rau lactic acid, piav qhia nws cov teebmeem los tiv thaiv melanogenic hauv melanocytes.
Whitening tyrosinase yog ib qho tseem ceeb enzyme nyob rau hauv lub synthesis ntawm melanin. Tag nrho glycosides ntawm Cistanche deserticola - ib qho chaw sib cais los ntawm cov tshuaj ntsuab suav tshuaj Cistanche deserticola tuaj yeem txo qis- tswj cov haujlwm ntawm tyrosinase. Cov nyhuv yog kev sib tw thim rov qab inhibition, uas tuaj yeem cuam tshuam cov tawv nqaij Pigmentation, ua kom zoo nkauj zoo nkauj zoo nkauj. Cov ntaub ntawv sim tau pom tias: thaum qhov concentration ntawm tag nrho glycosides ntawm Cistanche deserticola nyob rau hauv thaj tsam ntawm 0.5-3.0 mg·mL-1, nws muaj ib qho inhibitory. cuam tshuam rau kev ua ntawm tyrosinase, thiab kev sib raug zoo ntawm koob tshuaj tau pom nyob rau hauv thaj tsam ntawm 0 5-2.0 mg·mL-1.
Nyem kom paub tias cistanche yog dab tsi
Ntsiab lus:
melanogenesis; qab zib; qabzib; tyrosinase; tib neeg daim tawv nqaij sib npaug
1. Taw qhia
Melanogenesis yog txheej txheem ntawm melanin ntau lawm thiab yog qhov tseem ceeb rau kev tiv thaiv tawv nqaij. Melanin absorbs ultraviolet (UV) lub teeb thiab tiv thaiv daim tawv nqaij los ntawm kev puas tsuaj los ntawm UV teeb thiab dawb radicals [1]. Txawm li cas los xij, vim tias ntau ntau ntawm melanin ua rau hyperpigmentation xws li freckles thiab lentigo, uas tej zaum yuav xav tias tsis zoo, ntau kev tshawb fawb tau mob siab rau nrhiav cov khoom xyaw de-pigmentary zoo rau cov tshuaj pleev ib ce lossis tshuaj [2-4].
Qab Zib yog ib qho muaj zog humectant rau daim tawv nqaij moisturization thiab yog siv los ua cov khoom xyaw kom zoo nkauj rau cov tawv nqaij moisturizing nrog cov kev mob tshwm sim tsawg heev. Tsis tas li ntawd, cov piam thaj thiab cov piam thaj muaj feem cuam tshuam rau melanogenesis [5,6]. Glycosylation ntawm tyrosinase, ib qho tseem ceeb enzyme koom nrog hauv melanin synthesis, tuaj yeem hloov pauv, inhibiting nws txoj haujlwm catalytic thiab ua kom nws cov degradation [7]. Lub luag haujlwm ntawm cov suab thaj hauv melanogenesis tau raug qhia los ntawm cov kev tshawb fawb tshawb xyuas cov txiaj ntsig ntawm glycosylation ntawm pigmentation phenotype ntawm melanocytes thiab lub luag haujlwm ntawm cov piam thaj residues ntawm kev ua haujlwm catalytic ntawm tyrosinase [5-7]. Qee cov kev tshawb fawb tau tshaj tawm tias cov piam thaj derivatives tuaj yeem cuam tshuam tyrosinase kev loj hlob, cuam tshuam rau nws cov glycosylation. Piv txwv li, N-acetylglucosamine (NAG), ib qho amino hexose tsim physiologically los ntawm kev sib ntxiv ntawm ib pawg amino rau qabzib, cuam tshuam tyrosinase glycosylation, uas ua rau depigmenting los ntawm guinea npua daim tawv nqaij thiab tib neeg daim tawv nqaij [8].
Tsis tas li ntawd, cov kev tshawb fawb tsis ntev los no tau pom tias cov khoom sib txuas nrog cov suab thaj inhibit tyrosinase qhia lossis ua kom muaj zog ntxiv nrog rau hloov nws cov glycosylation. Piv txwv li, peb tau soj ntsuam qhov ua tau zoo ntawm galacturonic acid (GA), cov kua qaub qab zib uas yog oxidized daim ntawv ntawm galactose thiab cov ntsiab lus tseem ceeb ntawm pectin. Galacturonic acid exerts ib tug whitening nyhuv los ntawm cov kev cai ntawm tyrosinase kev ua si thiab qhia nyob rau hauv B16 murine melanoma hlwb thiab ib tug tib neeg daim tawv nqaij sib npaug [9]. Hauv lwm daim ntawv tshaj tawm, ib hom tshiab ntawm cyclic oligosaccharide, hu ua cyclic nitrosyl nigerose (CNN), tau pom qhov tsis muaj zog tab sis tseem ceeb cuam tshuam ncaj qha cuam tshuam rau kev ua haujlwm enzymatic ntawm tyrosinase, qhia txog ib qho kev ua tau zoo ntawm hypopigmentation [10]. Zoo ib yam li tyrosinase maturation los ntawm glycosylation kom zoo, kev qhia lossis kev ua ntawm CNN tuaj yeem yog lub hom phiaj ntawm cov tshuaj tiv thaiv melanogenic [11]. Txawm li cas los xij, ntau cov tshuaj tiv thaiv melanogenic muaj kev phiv loj heev, xws li vitiligo [12,13]. Yog li ntawd muaj kev txaus siab zoo rau kev nyab xeeb de-pigmentary compounds.
Ntawm no, peb tau tshawb xyuas cov tshuaj tiv thaiv melanogenic ntawm cov piam thaj ntawm B16 murine melanoma hlwb thiab tib neeg melanocytes. Tsis tas li ntawd, peb tau tshuaj xyuas cov ntaub so ntswg xim thiab cov txheej txheem epidermal uas siv cov ntaub so ntswg staining ntawm tib neeg daim tawv nqaij sib npaug. Raws li peb cov kev tshawb pom, peb xav tias cov nyhuv whitening ntawm qabzib yog nyob ntawm kev tsim cov lactic acid, ua rau tyrosinase inactivation.
2. Cov txiaj ntsig
2.1. Anti-Melanogenic Efficacy ntawm Glucose hauv B16 thiab NHMs
Txhawm rau tshawb xyuas cov nyhuv anti-melanogenic ntawm cov piam thaj, peb siv ob hom melanocytes, B16 melanoma hlwb (ib kab murine melanoma hlwb) thiab tib neeg melanocytes (NHMs). Ua ntej, peb txiav txim siab seb cov piam thaj puas muaj tshuaj lom rau B16 hlwb. Glucose tsis pom muaj cytotoxicity ntawm ntau txog 100 mM hauv B16 hlwb, raws li qhia hauv daim duab 1A. Raws li cov ntaub ntawv cytotoxicity, B16 hlwb tau kho nrog ntau qhov ntau ntawm cov piam thaj rau 72 h nyob rau hauv lub xub ntiag ntawm -melanocyte-stimulating hormone (MSH), uas yog inducer ntawm melanogenesis. Raws li pom hauv daim duab 1B, cov piam thaj kom meej meej thiab txo qis-tswj cov ntsiab lus ntawm melanin intracellular raws li koob tshuaj. Kojic acid (KA) tau siv los ua cov khoom siv los tiv thaiv melanogenesis vim nws feem ntau siv los ua cov khoom siv tshuaj pleev ib ce ntawm daim tawv nqaij [1,3,4]. Cov xim ntawm lysates hauv cov hlwb uas kho cov piam thaj yog sib dua li cov xim ntawm cov hlwb tswj (Daim duab 1C).
Tsis tas li ntawd, peb tau lees paub tias ntau npaum li cas melanin secreted rau hauv kab lis kev cai xov xwm txo qis thiab cov xim ntawm cov xov xwm brightened (Daim duab 1D). Tom ntej no, peb tshawb xyuas cov tshuaj tiv thaiv melanogenic ntawm cov piam thaj ntawm cov xim tsaus nti NHMs. Glucose ntawm qhov siab txog li 100 mM tsis yog cytotoxic ntev txog plaub 4 hnub (Daim duab 1E). Thaum cov ntsiab lus melanin tau txiav txim siab tom qab kev kho cov piam thaj ntawm NHMs rau 4 hnub, peb pom tias cov ntsiab lus melanin tau txo qis hauv cov koob tshuaj (Daim duab 1F). Ua ke, cov txiaj ntsig no qhia tau hais tias qabzib inhibits melanin synthesis hauv melanocytes.
Daim duab 1. Cov txiaj ntsig ntawm cov piam thaj ntawm B16 hlwb thiab tib neeg melanocytes (NHMs). (A) Cov txiaj ntsig ntawm cov piam thaj hauv kev muaj peev xwm ntawm B16 hlwb. (B) Intracellular melanin cov ntsiab lus hauv -MSH-stimulated B16 hlwb. Intracellular melanin cov ntsiab lus tau txiav txim siab siv cell lysates, raws li tau piav qhia hauv cov txheej txheem. (C) Cov xim ntawm cell lysate. (D) Extracellular melanin cov ntsiab lus tau txiav txim siab siv cov kab lis kev cai uas muaj melanin secreted tom qab qabzib thiab -MSH co-kev kho mob rau 72 teev. KA qhia kojic acid (100 µg/mL), uas tau siv los ua cov ntaub ntawv siv. Daim duab qhia cov xim ntawm kab lis kev cai xov xwm. (E) Kev cuam tshuam ntawm cov piam thaj rau ntawm kev muaj peev xwm ntawm NHMs. (F) Kev cuam tshuam ntawm qabzib ntawm melanin synthesis hauv NHMs. NHMs tau kho nrog qhov qhia tau hais tias muaj cov piam thaj rau 4 d, ntxuav, thiab lysed nrog NaOH los txiav txim siab cov ntsiab lus ntawm melanin intracellular. Cov ntsiab lus melanin tau kwv yees los ntawm kev nqus ntawm 405 nm thiab normalized los ntawm tag nrho cov ntsiab lus protein. Cov ntaub ntawv raug nthuav tawm raws li qhov nruab nrab ± SD ntawm tsawg kawg peb qhov kev ntsuas kev ywj pheej (*p <0.05, **p <0.01, ***p <0.001).
2.2. Whitening nyhuv ntawm Glucose ntawm 3D tib neeg daim tawv nqaij sib npaug
Txhawm rau txhawm rau txheeb xyuas qhov muaj peev xwm tiv thaiv melanogenic ntawm cov piam thaj, peb siv cov xim 3D tib neeg daim tawv nqaij qauv, MelanoDerm. Raws li tau piav qhia hauv Cov Khoom Siv thiab Cov Txheej Txheem, cov piam thaj tau siv rau hauv MelanoDerm rau 18 hnub, thiab kev muaj peev xwm ntawm tes tau txiav txim los ntawm CCK-8 kev soj ntsuam. Raws li pom hauv daim duab 2A, tsis muaj cov ntaub so ntswg cytotoxicity tau pom tom qab kev kho cov piam thaj rau 18 hnub. Cov ntaub so ntswg hloov xim tau soj ntsuam los ntawm kev yees duab. Raws li pom hauv daim duab 2B, cov ntaub so ntswg kho cov piam thaj yog xim xim dua li phosphate-buffered saline (PBS)-kho cov ntaub so ntswg. Tsis tas li ntawd, hematoxylin thiab eosin (H&E) staining qhia tias cov piam thaj tsis ua rau cov ntaub so ntswg tawg, thaum fontana-masson (F&M) staining pom tias cov piam thaj txo qis cov hyperpigmented melanocytes (raws li qhia los ntawm xub) nyob rau hauv lub basal txheej (Daim duab 2C) .
Txhawm rau tshawb xyuas ntxiv cov kev hloov pauv hauv cov ntsiab lus melanin, peb muab piv rau nws pib-fluorescence teeb liab ntawm melanin nyob rau hauv melanocyte txheej ntawm PBS- thiab cov ntaub so ntswg kho cov kua nplaum siv ob-photon excitation fluorescence (TPEF) microscopy, raws li qhia hauv daim duab 2D. Kev soj ntsuam ntawm cov duab no tau pom tias melanin ntim tau txo los ntawm kwv yees li 36 feem pua thiab TPEF teeb liab siv rau melanin hauv thaj tsam melanocyte-nplua nuj tau txo los ntawm kwv yees li 38 feem pua hauv cov ntaub so ntswg kho cov piam thaj piv nrog PBS-kho cov ntaub so ntswg.
Daim duab 2. Cov nyhuv ntawm cov piam thaj rau tib neeg daim tawv nqaij sib npaug, MelanoDerm. (A) Kev muaj peev xwm ntawm tib neeg cov tawv nqaij sib npaug kho nrog cov piam thaj. (B) Tib neeg daim tawv nqaij sib npaug (MelanoDerm; n=3) tau kho cov piam thaj rau 18 d, thiab tom qab ntawd thaij duab. Tus nqi ∆L qhia txog qhov pom kev sib piv nrog PBS-kho cov ntaub so ntswg. (C) H&E thiab F&M staining ntawm cov ntaub so ntswg. Cov slides tau kho nyob rau hauv ib tug formaldehyde tov thiab embedded nyob rau hauv paraffin wax rau staining (scale bar, 5{{10}} µm). Cov xub dub qhia cov xim melanocytes. (D) Melanin imaging (200 × 200 × 60 µm3) ntawm tib neeg daim tawv nqaij sib npaug tau ua los ntawm TPEF microscopy. Pseudocolored (liab) signals qhia melanin (scale bar, 50 µm). Cov duab qhia txog qhov ntau ntawm melanin ntim thiab TPEF cov cim. Cov ntaub ntawv raug nthuav tawm raws li qhov nruab nrab ± SD ntawm tsawg kawg peb qhov kev ntsuas kev ywj pheej (*p <0.05, ***p <0.001).
2.3. Cov txiaj ntsig ntawm Glucose ntawm Kev Tshaj Tawm ntawm Melanogenic Proteins hauv Melanocytes
Tom ntej no, txhawm rau txheeb xyuas cov txheej txheem depigmentation ntawm cov piam thaj hauv melanocytes, peb tau soj ntsuam nws cov txiaj ntsig ntawm kev qhia ntawm melanogenic enzymes xws li tyrosinase thiab Tyrp-1 hauv B16 hlwb thiab NHMs. B16 hlwb raug kho nrog qabzib rau lub sijhawm qhia nyob rau hauv muaj -MSH. Tom qab ntawd, qib protein ntau ntawm tyrosinase thiab Tyrp-1 tau txiav txim siab los ntawm Western blot assay (Daim duab 3A). Kev qhia theem ntawm tyrosinase thiab Tyrp-1 tsis tau txo qis los ntawm cov piam thaj thaum twg los tau. Tsis tas li ntawd, cov ntawv sau tseg ntawm tyrosinase tsis cuam tshuam los ntawm cov piam thaj hauv -MSH-stimulated B16 hlwb (Daim duab 3B). Zoo ib yam li B16 hlwb, qib protein ntau ntawm tyrosinase, Tyrp-1, thiab MITF tsis cuam tshuam los ntawm cov piam thaj (Daim duab 3C) hauv NHM hlwb kho nrog cov piam thaj, thiab mRNA qib ntawm tyrosinase thiab Tyrp-1 kuj tsis tau. txo qis, tab sis kuj nce me ntsis los ntawm cov piam thaj (Daim duab 3D).
Daim duab 3. Cov txiaj ntsig ntawm cov piam thaj ntawm kev qhia ntawm melanogenic proteins hauv B16 hlwb thiab NHMs. (A, B) B16 hlwb raug kho nrog -MSH rau lub sijhawm qhia thaum muaj lossis tsis muaj 20 mM qabzib. Tom qab ntawd, Western blot (A) thiab qRT-PCR (B) tau ua. (C) NHMs tau kho nrog qhov qhia pom muaj suab thaj rau 48 teev. Tom qab ntawd, Western blot assay tau ua. (D) NHMs tau kho nrog lub sijhawm qhia thaum muaj 50 mM qabzib. Tom qab ntawd, kev tshuaj xyuas qRT-PCR tau ua. Cov ntaub ntawv raug nthuav tawm raws li qhov nruab nrab ± SD ntawm tsawg kawg peb qhov kev ntsuas ywj pheej.
2.4. Cov nyhuv ntawm Glucose ntawm Tyrosinase Kev Ua Haujlwm
Txhawm rau txhawm rau txheeb xyuas qhov kev ua haujlwm ntawm cov piam thaj, peb tau sim yog tias nws muaj kev cuam tshuam rau cov nceb tyrosinase kev ua haujlwm. Raws li pom hauv daim duab 4A, peb pom tias cov piam thaj tsis muaj kev cuam tshuam rau cov nceb tyrosinase kev ua haujlwm, qhia tias cov piam thaj tsis cuam tshuam ncaj qha rau tyrosinase. Peb tom ntej no tau ua tag nrho intracellular tyrosinase kev ua ub no siv cov kua nplaum-kho cell lysates los ntawm B16 hlwb thiab NHMs. Interestingly, intracellular tyrosinase kev ua si tau inhibited nyob rau hauv ib koob tshuaj raws li nyob rau hauv cov piam thaj-kho B16 hlwb nyob rau hauv lub xub ntiag ntawm -MSH (Daim duab 4B). Hauv NHMs, cov piam thaj kuj inhibited intracellular tyrosinase kev ua haujlwm (Daim duab 4C). Cov ntaub ntawv no txhawb nqa qhov ua tau tias cov piam thaj tsis ncaj qha ua rau tyrosinase hauv melanocytes.
Daim duab 4. Kev cuam tshuam ntawm cov piam thaj rau ntawm kev ua tyrosinase. (A) Cov nyhuv ntawm cov piam thaj ntawm cov nceb tyrosinase kev ua haujlwm hauv lub cev tsis muaj cell. (B, C) Cellular tyrosinase kev ua ub no. (B) B16 hlwb raug kho nrog qhov qhia tau tias muaj cov piam thaj hauv 24 teev. Tom qab ntawd, qhov kev ntsuam xyuas ntawm tes ntawm tyrosinase tau ua, raws li tau piav qhia hauv cov txheej txheem. (C) NHMs tau kho nrog 50 mM qabzib rau lub sijhawm qhia. Tom qab ntawd, qhov kev ntsuam xyuas ntawm tes ntawm tyrosinase tau ua, raws li tau piav qhia hauv cov txheej txheem. Lub cellular tyrosinase kev ua haujlwm tau normalized los ntawm tag nrho cov ntsiab lus protein. Cov ntaub ntawv raug nthuav tawm raws li qhov nruab nrab ± SD ntawm tsawg kawg yog peb qhov kev ntsuas ywj pheej (*p < 0.05, **p < 0.01, ***p < 0.001).
2.5. Tyrosinase Inactivation los ntawm Kev Tsim Cov Lactic Acid hauv Glucose-Treated Melanocytes
Glucose hloov mus rau hauv cov cellular metabolite lactate, uas yog lactic acid hauv kev daws thiab tau tshaj tawm tias yuav ua tau zoo hauv kev kho cov kab mob pigmentary [14,15]. Yog li, peb xav tias cov piam thaj hloov mus rau hauv lactic acid hauv melanocytes thiab qhov nce qib ntawm lactic acid inhibit melanogenesis los ntawm tyrosinase inactivation. Txhawm rau ntsuas qhov kev xav no, peb thawj zaug ntsuas qhov tsim cov lactic acid hauv xov xwm los ntawm cov piam thaj kho melanocytes. Raws li qhov xav tau, cov piam thaj tau nce siab- tswj cov lactic acid cov ntsiab lus hauv B16 hlwb-cultured media (Daim duab 5A). Tsis tas li ntawd, vim tias lactic acid paub ncaj qha inhibit tyrosinase kev ua haujlwm [15], peb ntsuas yog tias lactic acid suppressed nceb tyrosinase kev ua haujlwm. Raws li pom nyob rau hauv daim duab 5B, lactic acid ua rau inhibited nceb tyrosinase kev ua, tsis zoo li qabzib. Cov txiaj ntsig no qhia tau tias kev hloov pauv ntawm cov piam thaj mus rau lactic acid muaj cov nyhuv anti-melanogenic ntawm tyrosinase inactivation los ntawm lactic acid.
Daim duab 5. Kev tsim cov lactate los ntawm cov piam thaj thiab cov nyhuv ntawm lactic acid ntawm kev ua tyrosinase. (A) Lactate ntau lawm hauv cov piam thaj-kho B16 hlwb. (A) B16 hlwb raug kho nrog cov qhia pom muaj suab thaj rau 3 d. Tom qab ntawd, ib qho kev ntsuam xyuas lactate tau ua los ntawm kev siv cov kab lis kev cai, raws li tau piav qhia hauv tshooj lus. (B) Cov nyhuv ntawm lactic acid ntawm nceb tyrosinase kev ua haujlwm hauv lub cev tsis muaj cell. Cov ntaub ntawv raug qhia raws li qhov nruab nrab ± SD ntawm tsawg kawg yog peb qhov kev ntsuas ywj pheej (*p < 0.05, **p < 0.01, ***p < 0.001) .
3. Kev sib tham
Qab zib los yog cov khoom qab zib los ntawm cov khoom qab zib feem ntau yog siv los ua cov khoom xyaw kom zoo nkauj rau kev tiv thaiv tawv nqaij thiab kev tswj lub cev. Piv txwv li, raffinose tsub kom mTOR-ywj siab autophagy thiab txo cov cell tuag nyob rau hauv UVB-irradiated keratinocytes, qhia tau hais tias lub ntuj tus neeg sawv cev raffinose muaj peev xwm muaj nuj nqis nyob rau hauv limiting photodamage [16]. Trehalose thiab sucrose yog cov tshiab activators ntawm autophagy nyob rau hauv tib neeg keratinocytes los ntawm ib tug mTOR-kev ywj pheej txoj kev [17]. Cov kev tshawb pom no muab kev pom tshiab rau hauv cov suab thaj-kho cov kev cai ntawm autophagy hauv keratinocytes. Nyob rau hauv cov ntaub ntawv ntawm cov piam thaj, cov tshuaj pleev xim tau pom tias yuav ua rau claudin -1 thiab filaggrin qhia nyob rau hauv tus nas qauv ntawm atopic dermatitis thiab keratinocyte kab lis kev cai, qhia tau hais tias nws muaj anti-inflammatory nyhuv los ntawm kho daim tawv nqaij barrier muaj nuj nqi [18]. Tsis tas li ntawd, cov piam thaj inhibits proliferation thiab txhim kho qhov sib txawv ntawm daim tawv nqaij keratinocytes [19]. Yog li, cov piam thaj tswj ntau yam ntawm epidermal physiology, xws li daim tawv nqaij barrier functions thiab keratinocyte hydration qib.
Qab Zib tuaj yeem ua cov tshuaj depigmentary los ntawm ntau lub tshuab sib txawv uas koom nrog tyrosinase. Piv txwv li, qee cov neeg ua haujlwm inhibit tyrosinase maturation, thaum lwm tus neeg ua haujlwm ua rau inhibition ntawm tyrosinase noob qhia lossis kev ua haujlwm [5,8-10]. Txawm li cas los xij, qee qhov kev tshawb fawb tau tshawb xyuas cov txheej txheem hauv qab ntawm depigmentation los ntawm cov piam thaj.
Txhawm rau txiav txim siab cov txiaj ntsig ntawm cov piam thaj ntawm melanogenesis, yav dhau los peb tau tsom mus rau lub siab X receptors (LXRs), uas yog ligand-activated nuclear receptors uas ua lub luag haujlwm tseem ceeb hauv lipid metabolism thiab cholesterol homeostasis [20]. Peb pom tias daim siab X receptor activation inhibits melanogenesis los ntawm kev nrawm ntawm extracellular signal-regulated kinase (ERK)-mediated microphthalmia-associated transcription factor (MITF) degradation [21].
Tsis tas li ntawd, cov piam thaj yog ib qho endogenous LXR ligand [22]. Yog li, peb xav tias cov piam thaj muaj cov tshuaj tiv thaiv melanogenic vim yog kev ua haujlwm ntawm LXR-nyob ntawm txoj kev. Txawm li cas los xij, raws li pom hauv daim duab 3C, cov piam thaj tsis hloov pauv cov theem qhia ntawm tyrosinase lossis MITF, txawm hais tias LXR ua kom txo qis cov qib ntawm cov proteins hauv melanocytes. Yog li ntawd, peb tau txiav txim siab tias cov piam thaj muaj cov teebmeem depigmenting ntawm melanocytes ywj pheej ntawm LXR activation.
Glucose yog lub hauv paus tseem ceeb rau kev tsim hluav taws xob, thiab nws yog hydrolyzed los ntawm cov tshuaj tiv thaiv kab mob ntawm ntau cov enzymes, hu ua glycolysis. Ntau cov kev tshawb fawb tau pom tias glycolysis tsuas muaj ib qho khoom kawg nkaus xwb, lactic acid, txawm tias nyob rau hauv aerobic lossis anaerobic mob. Nyob rau hauv aerobic tej yam kev mob (O2), lactate yog siv raws li lub substrate ntawm mitochondrial lactate dehydrogenase (MLD). LDHs hloov nws mus rau pyruvate uas nkag mus rau lub voj voog tricarboxylic acid (TCA). Nyob rau hauv cov xwm txheej anaerobic (N2), lactate tau sau hauv cytosol. Yog li ntawd, txoj kev glycolysis pib nrog cov piam thaj raws li nws cov substrate thiab xaus nrog kev tsim cov lactate ua nws cov khoom tseem ceeb kawg [23]. Tsis tas li ntawd, David et al. ntsuas qhov feem ntawm cov piam thaj uas hloov mus rau lactic acid lossis pyruvate hauv tib neeg melanocyte [24]. Feem ntau ntawm cov metabolites ntawm qabzib yog lactic acid ntau dua li pyruvate.
Lactic acid yog alpha hydroxy acid (AHA); cov kua qaub no tau siv dav hauv cov tshuaj pleev ib ce ua cov tshuaj pleev ib ce [25]. Tsis tas li ntawd, lactic acid inhibits melanin tsim los ntawm ncaj qha inhibiting tyrosinase kev ua si, ib qho kev ywj pheej ntawm nws cov acidic xwm, uas txhais tau hais tias lactic acid cuam tshuam rau pigmentary lesions yog vim tsis tsuas yog rau acceleration ntawm epidermal cell turnover tab sis kuj ncaj qha inhibition ntawm melanin tsim nyob rau hauv melanocytes [15]. Yog li, peb xav tias cov piam thaj tuaj yeem ua rau nws cov nyhuv anti-melanogenic los ntawm kev tsim cov lactic acid vim tias cov piam thaj tuaj yeem hloov mus rau lactic acid.
Raws li qhov xav tau, peb pom tias kev kho cov piam thaj ua rau muaj cov lactic acid ntau lawm hauv melanocytes (Daim duab 5A). Tsis tas li ntawd, peb tau lees paub tias lactic acid muaj zog thiab ncaj qha inhibited tyrosinase kev ua haujlwm (Daim duab 5B). Usuki et al. kuj pom tau tias lactic acid txo qis intracellular tyrosinase kev ua haujlwm hauv B16 hlwb thiab tib neeg HM3KO hlwb [15]. Hauv tsab ntawv tshaj tawm, mRNA thiab qib protein ntawm tyrosinase thiab Tyrp-1 tsis cuam tshuam los ntawm lactic acid. Ua ke, cov ntaub ntawv no qhia tau hais tias qabzib nce lactic acid ntau lawm thiab tias cov lactic acid no ncaj qha inhibits tyrosinase kev ua haujlwm yam tsis muaj kev cuam tshuam cov qib qhia cov noob, qhia tias qabzib muaj cov nyhuv anti-melanogenic hauv melanocytes ntawm indirect tyrosinase inactivation nyob ntawm lactic acid ntau lawm. Txawm li cas los xij, kev sim ntxiv yog tsim nyog los xyuas lub luag haujlwm ntawm lactic acid thiab qabzib hauv depigmentation.
Cov ntaub ntawv sau los ntawm qhov kev tshawb fawb no muab pov thawj ua pov thawj txhawb nqa cov khoom siv ntawm cov tshuaj pleev ib ce raws li kev ua kom zoo nkauj zoo nkauj nrog rau cov tshuaj moisturizing uas tuaj yeem siv nyab xeeb hauv cov tshuaj pleev ib ce thiab tshuaj tshuaj.
4. Cov ntaub ntawv thiab cov txheej txheem
4.1. Khoom siv
D-glucose, -MSH, kojic acid (KA), L-tyrosine, L-DOPA, thiab lactic acid tau yuav los ntawm Sigma-Aldrich (St. Louis, MO, USA). Antibodies tiv thaiv tyrosinase thiab actin tau yuav los ntawm Abcam (Cambridge, UK). Antibody tiv thaiv Tyrp-1 tau yuav los ntawm Santa Cruz Biotechnology (CA, USA). Antibody tiv thaiv MITF tau yuav los ntawm Proteintech (lub nroog, IL, USA).
4.2. Cell Culture thiab Viability Assay
Peb yuav B16 murine melanoma cells, Dulbecco's modified Eagle's medium (DMEM), thiab fetal bovine serum (FBS) los ntawm American Type Culture Collection (ATCC, Manassas, VA, USA). B16 hlwb raug coj los rau hauv DMEM uas muaj 4500 mg/L siab qabzib (ATCC 30-2002) raws li kev pom zoo los ntawm cov chaw tsim tshuaj paus (ATCC) ntxiv nrog 5 feem pua FBS, thiab incubated ntawm 37 ◦C nyob rau hauv ib tug humidified huab cua uas muaj 95 feem pua ntawm huab cua thiab 10% CO2. Darkly pigmented thawj NHMs tau yuav los ntawm Thermo Fisher Scientific (#C2025C; Waltham, MA, USA). Cells tau coj mus rau hauv nruab nrab 254 (#M254500) ntxiv nrog Human Melanocyte Growth Supplement (#S0025) thiab incubated ntawm 37 ◦C hauv qab 5 feem pua CO2 cua. Rau kev sim, thawj NHMs ntawm nqe 4 thiab 7 tau siv. Kev muaj peev xwm ntawm cov kab lis kev cai tau raug soj ntsuam los ntawm cov khoom siv Cell suav -8 (CCK-8) raws li tau piav qhia los ntawm cov chaw tsim khoom (DOJINDO, Tokyo, Nyiv).
4.3. Kev ntsuas ntawm Melanin Cov ntsiab lus
Cov ntsiab lus melanin tau txiav txim siab raws li tau piav qhia hauv cov ntaub ntawv dhau los [2–4]. Luv luv, B16 hlwb raug kho nrog qhov qhia tau hais tias muaj cov piam thaj hauv qhov muaj -MSH (200 nM) rau 72 teev. NHMs tau kho nrog qhov qhia pom muaj suab thaj rau 4 d. Tom qab ntawd, tag nrho cov hlwb raug ntxuav nrog phosphate-buffered saline (PBS) thiab yaj hauv 1 N NaOH ntawm 60 ◦C rau 1 h. Cell lysates tau pauv mus rau 96-zoo phaj, thiab nqus tau ntsuas ntawm 405 nm. Cov txiaj ntsig tau normalized raws li cov protein ntau hauv txhua tus qauv zoo.
4.4. Mushroom Tyrosinase Activity Assay
Peb tau tshawb xyuas qhov cuam tshuam ncaj qha ntawm qhov qhia tau tias muaj cov piam thaj hauv cov nceb tyrosinase kev ua haujlwm. Luv luv, 100 µL ntawm phosphate tsis muaj qabzib yog tov nrog nceb tyrosinase (10 units / zoo) thiab ua ke nrog 50 µL ntawm 0.03 feem pua L-tyrosine lossis L-DOPA hauv dej distilled. Tom qab ntawd, qhov sib tov yog incubated ua ke ntawm 37 ◦C rau 10 min, thiab absorbance yog ntsuas ntawm 405 nm. Kojic acid (KA), uas paub zoo los tiv thaiv tyrosinase tus neeg sawv cev, tau siv los ua cov ntaub ntawv siv.
4.5. Intracellular Tyrosinase Activity Assay
Luv luv, B16 hlwb los yog NHMs tau kho nrog cov qhia pom cov piam thaj rau lub sijhawm qhia. Tom qab ntawd, cov hlwb raug ntxuav nrog PBS thiab lysed los ntawm incubation nyob rau hauv 50 mM phosphate buffer (pH 6.8) uas muaj 1 feem pua Triton X-100 thiab 0.1 mM phenylmethyl-sulfonyl fluoride. Cellular lysates ces centrifuged ntawm 12, 000 rpm ntawm 4 ◦C rau 20 min. Lub supernatant uas muaj cellular tyrosinase tau sau thiab cov ntsiab lus protein tau txiav txim rau normalization. Lub cellular extract tau incubated nrog L-DOPA nyob rau hauv phosphate tsis thiab dopachrome tsim tau soj ntsuam los ntawm kev ntsuas absorbance ntawm 405 nm nyob rau hauv 30 min.
4.6. Kev cais RNA thiab Real-Time Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR)
Txhawm rau txiav txim siab tus txheeb ze mRNA qhia ntawm cov noob xaiv, tag nrho RNA raug cais nrog TRIzol (Invitrogen, CA, USA), raws li cov chaw tsim khoom cov lus qhia, thiab 4 µg RNA tau thim rov qab rau hauv cDNA siv RT-premix (Bioneer, Seoul, South. Kauslim). Quantitative PCR tau ua tiav siv ABI 7500 Fast Real-Time PCR System (Applied Biosystems, Foster City, CA, USA). QRT-PCR primer sets rau tyrosinase thiab Tyrp-1 tau muas los ntawm Applied Biosystems, thiab TaqMan Gene Expression Assay kits (Applied Biosystems) tau siv rau kev nthuav dav. Lub hom phiaj gene qhia tau normalized rau cov tsev tu noob encoding ribosomal protein lateral stalk subunit P0 (RPLP0). Tus txheeb ze quantization tau ua los ntawm kev sib piv ∆∆ Ct txoj kev raws li cov chaw tsim khoom cov lus qhia.
4.7. Western Blotting
Cells raug ntxuav ob zaug nrog txias PBS thiab ces lysed nyob rau hauv cov dej khov-txias hloov RIPA tsis (Cell Signaling Technology, MA, USA) uas muaj protease inhibitors (Calbiochem, La Jolla, CA, USA). Tag nrho cov protein concentration tau txiav txim siab, thiab cov proteins tau daws los ntawm SDS-PAGE ntawm 4-12 feem pua gradient Bis-Tris gels (Thermo Fisher Scientific, Waltham, MA, USA), pauv mus rau nitrocellulose membranes (Thermo Fisher Scientific). Tom qab hloov mus, daim nyias nyias tau thaiv hauv 5 feem pua txhiab tshuaj. Membranes tau incubated nrog thawj cov tshuaj tiv thaiv ntawm 4 ◦C rau 24 teev, ntxuav nrog Tris-buffered saline uas muaj 0.1 feem pua Tween-20 (TBST), thiab raug peroxidase-conjugated secondary antibodies rau 1 h ntawm chav tsev kub. Membranes tau muab yaug peb zaug nrog TBST. Lub teeb liab chemiluminescent tau tsim los siv Western blotting ECL reagent (GE Healthcare, Hatfield, UK).
4.8. Peb-Dimensional (3D) Tib neeg daim tawv nqaij sib npaug
Peb siv MelanoDerm (MEL-300-B; MatTek Corp., Ashland, MA, USA) raws li tib neeg daim tawv nqaij qauv. Qhov no siv tau, rov tsim dua, 3D tib neeg daim tawv nqaij sib npaug tau muab los ntawm cov neeg pub dawb thiab muaj cov melanocytes thiab keratinocytes. MelanoDerm tau loj hlob ntawm huab cua-kua interface hauv EPI-100-NMM-113 nruab nrab (MatTek Corp, Ashland, MA, USA). Ua ntej kho cov piam thaj, cov ntaub so ntswg tau ntxuav nrog 1 mL PBS kom tshem tawm cov khoom seem. Glucose tau yaj hauv PBS. Qhov kawg concentration ntawm qabzib yog 2 feem pua. Cov qauv tswj tau raug kho nrog PBS nkaus xwb. Glucose tau siv rau MelanoDerm hnub 1, 4, 6, 8, 11, 13, thiab 15. Tom qab 18 hnub, MelanoDerm cov ntaub so ntswg tau kho nyob rau hauv 4 feem pua buffered formaldehyde, embedded nyob rau hauv paraffin, txiav mus rau ib tug tuab ntawm 3 µm, thiab raug. rau H&E thiab F&M staining. Kev ua tau zoo ntawm cov qauv ntaub so ntswg tau soj ntsuam siv Cell Counting Kit-8 (CCK-8) raws li tau piav qhia los ntawm cov chaw tsim khoom (DOJINDO, Tokyo, Nyiv). Cov pigmentation ntawm MelanoDerm tau soj ntsuam los ntawm kev sib piv cov kev hloov pauv hauv tus nqi L *.
4.9. Ob-Photon Excitation Fluorescence (TPEF) Duab
Txhawm rau pom qhov kev faib tawm ntawm melanin hauv 3D tib neeg daim tawv nqaij sib npaug, peb tau ua TPEF duab, raws li tau piav qhia hauv peb cov ntawv tshaj tawm dhau los [3,4]. Luv luv, txhua qhov kev npaj MelanoDerm tau kho hauv 4 feem pua ntawm formalin rau 24 teev ntawm 4 ◦C thiab tom qab ntawd ntxuav nrog PBS / 0.1 feem pua BSA (bovine serum albumin, Merck, Branchburg, NJ, USA). Cov TPEF cov duab tau txais los ntawm cov txheej txheem basal los ntsuas intracellular melanin hauv txheej melanocyte. Cov txheeb ze TPEF teeb liab intensities rau melanin nyob rau hauv qhov ntsuas ntim tau quantified siv Image-Pro Premier 3D software (Media Cybernetics, Inc., Bethesda, MD, USA).
4.10. L-lactate Assay
B16 hlwb tau noob ntawm 1.0 × 105 hlwb ib qhov dej hauv ib lub qhov dej 12-zoo phaj. Tom qab kev kho mob nrog cov piam thaj rau 3 hnub, cov qib lactate extracellular tau suav nrog siv L-lactate colorimetric assay kit (Abcam, ab65331, Cambridge, UK) raws li cov chaw tsim khoom raws tu qauv.
4.11. Kev txheeb cais
Cov ntaub ntawv raug nthuav tawm raws li txhais tau tias ± SDs (tus qauv sib txawv), thiab qhov tseem ceeb ntawm cov ntaub ntawv tau txiav txim los ntawm Tub Ntxhais Kawm t-test. P-tus nqi < 0.05 tau suav tias yog qhov tseem ceeb.
Tus sau kev koom tes:
Conceptualization, H.-JK, JL, thiab CSL; Cov ntaub ntawv curation, SHL; Kev Tshawb Fawb, SHL; Methodology, SHL, I.-HB, thiab E.-SL; Kev saib xyuas, JL, thiab CSL; Kev Sau Ntawv—thawj tsab ntawv, SHL, thiab CSL; Kev Sau Ntawv- tshuaj xyuas thiab kho, JL Txhua tus kws sau ntawv tau nyeem thiab pom zoo rau cov ntawv luam tawm ntawm cov ntawv sau.
Nyiaj txiag:
Qhov kev tshawb fawb no tau txais nyiaj los ntawm Basic Science Research Program los ntawm National Research Foundation of Kauslim (NRF) tau txais nyiaj los ntawm Ministry of Education (Grant Number: 2018R1D1A1B07049402).
Kev tsis sib haum xeeb ntawm kev txaus siab:
Cov kws sau ntawv tshaj tawm tsis muaj kev sib cav txog kev txaus siab.
Cov ntawv luv
MSH - melanocyte-stimulating hormone
Tyrosinase-related protein 1
MITF microphthalmia cuam tshuam nrog kev hloov pauv
NHMs tib neeg melanocytes
TPEF ob-photon excitation fluorescence
LXR lub siab X receptor
AHAs alpha hydroxy acids
H&E hematoxylin thiab eosin
F&M Fontana-Masson
Cov ntaub ntawv
1. Swalwell, H.; Latimer, J.; Haywood, RM; Birch-Machin, MA Tshawb xyuas lub luag haujlwm ntawm melanin hauv UVA / UVB thiab hydrogen peroxide-Induced cellular thiab mitochondrial ROS ntau lawm thiab mitochondrial DNA puas nyob rau hauv tib neeg melanoma hlwb. Dawb Radic. Biol. Med. 2012, 52, 626–634. [CrossRef]
2. Lee, CS; Jang, WH; Park, M.; Jung, K.; Baek, HS; Yog, YH; Park, YH; Lim, KM Ib qho tshiab adamantyl benzylbenzamide derivative, AP736, suppresses melanogenesis los ntawm inhibition ntawm cAMP-PKA-CREB-Activated microphthalmia-Associated transcription factor thiab tyrosinase qhia. Exp. Dermatol. Xyoo 2013, 22, 762–764. [CrossRef] [PubMed]
3. Lee, JH; Li, ES; Ib, IH; Hwang, JA; Kim, SH; Kim, DY; Park, NH; Rho, HS; Kim, YJ; Aw, SG; ua al. Antimelanogenic Efficacy ntawm Melasolv (3,4,5-Trimethoxycinnamate Thymol Ester) hauv melanocytes thiab peb-dimensional tib neeg daim tawv nqaij sib npaug. Daim tawv nqaij Pharmacol. Physiol. 2017, 30, 190–196. [CrossRef] [PubMed]
4. Bae, IH; Li, ES; Yog, JW; Li, SH; Koj, JY; Kim, YJ; Li, TR; Kim, DY; Lee, CS Mannosylerythritol lipids inhibit melanogenesis ntawm suppressing ERK-CREB-MITF-Tyrosinase signaling nyob rau hauv tib neeg melanocytes thiab ib tug peb-dimensional tib neeg daim tawv nqaij sib npaug. Exp. Dermatol. Xyoo 2019, 28, 738–741. [CrossRef] [PubMed]
5. Bin, BH; Kim, ST; Bhia, J.; Li, TR; Cho, EG Kev txhim kho cov piam thaj raws li cov tshuaj tiv thaiv Melanogenic. Int. J. Mol. Sci. 2016, 17, 583. [CrossRef]
6. Kumari, S.; Tien Guan Thng, S.; Kumar Verma, N.; Gautam, HK Melanogenesis Inhibitors. Acta. Derm. Venereol. Xyoo 2018, 98, 924–931. [CrossRef]
7. Ando, H.; Kondoh, H.; Ichihashi, M. Hnov, VJ Txoj Haujlwm los txheeb xyuas cov inhibitors ntawm melanin biosynthesis ntawm kev tswj xyuas zoo ntawm tyrosinase. J. Invest Dermatol. 2007, 127, 751–761. [CrossRef]
8. Hwang, JS; Li, HY; Lim, TY; Kim, kuv; Yoon, TJ Kev cuam tshuam ntawm tyrosinase glycosylation los ntawm N-acetylglucosamine thiab nws cov teebmeem depigmenting hauv guinea npua daim tawv nqaij thiab tib neeg daim tawv nqaij. J. Dermatol. Sci. 2011, 63, 199–201. [CrossRef]
9. Lee, CS; Baek, HS; Ib, IH; Choi, SJ; Kim, YJ; Li, JH; Kim, JW Depigmentation kev ua tau zoo ntawm galacturonic acid los ntawm kev tswj hwm tyrosinase hauv B16 murine melanoma hlwb thiab peb-dimensional tib neeg daim tawv nqaij sib npaug. Clin. Exp. Dermatol. Xyoo 2018, 43, 708–712. [CrossRef]
10. Nakamura, S.; Kunikata, T.; Matsumoto, Y.; Hana, T.; Harashima, UA; Nishimoto, T.; Ushio, S. Cov teebmeem ntawm cov uas tsis yog-Cyclodextrin cyclic carbohydrate rau nas melanoma hlwb: Cov yam ntxwv ntawm hom tshiab hypopigmented qab zib. PLoS IB 2017, 12, e0186640. [CrossRef]
11. Khan, MT Novel tyrosinase inhibitors los ntawm cov peev txheej ntuj-Lawv kev tshawb fawb. Curr. Med. Chem. 2012, 19, 2262–2272. [CrossRef] [PubMed]
12. Solano, F.; Briganti, S.; Picardo, M.; ib. Ghanem, G. Hypopigmentingagents: Kev tshuaj xyuas tshiab ntawm kev lom neeg, tshuaj lom neeg thiab kev kho mob. Pigment. Cell. Res. 2006, 19, 550–571. [CrossRef] [PubMed]
13. Lee, CS; Yog, YH; Baek, HS; Park, M.; Kim, JH; Shin, HJ; Park, NH; Li, JH; Park, YH; Shin, SS; ua al. Cov teebmeem sib txawv ntawm tsib de-pigmentary compounds, rhododendron, raspberry ketone, monobenzone, rucinol, thiab AP736 ntawm melanogenesis thiab kev muaj peev xwm ntawm tib neeg epidermal melanocytes. Exp. Dermatol. 2016, 25, 44–49. [CrossRef] [PubMed]
14. Mulukutla, BC; Khan, S.; Lange, A.; Hu, WS Glucose metabolism hauv mammalian cell culture: New insights for tweaking vintage pathways. Kev xav. Biotechnol. Xyoo 2010, 28, 476–484. [CrossRef]
15. Usuki, A.; Awashi, A.; Saib, H.; Ochiai, Y.; Ichihashi, M. Funasaka, Y. Cov nyhuv inhibitory ntawm glycolic acid thiab lactic acid ntawm melanin synthesis hauv melanoma hlwb. Exp. Dermatol. 2003, 12, 43–50. [CrossRef]
16. Lin, S.; Li, L.; Li, M.; Gu, H.; Chen, X. Raffinose nce autophagy thiab txo cov cell tuag hauv UVB-Irradiated keratinocytes. J. Phom. Photobiol. B 2019, 201, 111653. [CrossRef]
17. Chen, X.; Li, M.; Li, L.; Xu, S.; Huang, D.; Ju, M.; Huang, J.; Chen, K.; Gu, H. Trehalose, sucrose, thiab raffinose yog cov tshiab activators ntawm autophagy nyob rau hauv tib neeg keratinocytes los ntawm ib tug mTOR-Independent txoj kev. Sci. Rep. 2016, 6, 28423. [CrossRef]
18. Yamada, K.; Matsushita, K.; Wang, J.; Kanekura, T. Topical Glucose Induces Claudin-1 thiab Filaggrin Expression nyob rau hauv tus nas qauv ntawm Atopic Dermatitis thiab nyob rau hauv Keratinocyte Culture, Exerting Anti-Inflammatory Effects los ntawm Kho daim tawv nqaij Barrier Function. Acta. Derm. Venereol. 2018, 98, 19–25. [CrossRef]
19. Spravchikov, N.; Sizyakov, G.; Gartsbein, M. Accili, D.; Tennenbaum, T.; Wertheimer, E. Glucose cuam tshuam rau ntawm daim tawv nqaij keratinocytes: Qhov cuam tshuam rau cov tawv nqaij mob ntshav qab zib. Diabetes 2001, 50, 1627–1635. [CrossRef]
20. Castrillo, A.; Tontonoz, P. Nuclear receptors nyob rau hauv macrophage biology: Nyob rau ntawm txoj kev sib tshuam ntawm lipid metabolism thiab o. Annu. Rev. Cell. Dev. Biol. 2004, 20, 455–480. [CrossRef]
21. Lee, CS; Park, M.; Han, J.; Li, JH; Ib, IH; Choi, H.; Tub, ED; Park, YH; Lim, KM Liver X receptor activation inhibits melanogenesis los ntawm kev nrawm ntawm ERK-Mediated MITF degradation. J. Kev nqis peev. Dermatol. 2013, 133, 1063–1071. [CrossRef] [PubMed]
22. Mitro, N.; Mas, PA; Vargas, L.; Godio, C.; Hampton, E.; Molteni, V.; Kreusch, UA; Saez, E. Lub nuclear receptor LXR yog cov kua nplaum nplaum. Xwm Txheej 2007, 445, 219–223. [CrossRef] [PubMed]
23. Schurr, A. Carbohydrate; IntechOpen: London, UK, 2017; ib., 21–35.
24. Scott, D.; Richardson, UA; Filipp, F.; Knutzen, C.; Chiang, G.; Ronai, Z.; Osterman, UA; Smith, J. Comparative metabolic Flux profiling of melanoma cell kab: Tshaj li cov nyhuv Warburg. J. Biol. Chem. 2011, 286, 42626–42634. [CrossRef] [PubMed]
25. Tang, SC; Yang, JH Dual Effects of Alpha-Hydroxy Acids ntawm daim tawv nqaij. Molecules 2018, 23, 863. [CrossRef]
For more information:1950477648nn@gmail.com
