Sirtuins hauv raum Kev Noj Qab Haus Huv Thiab Kab Mob Ⅰ
Feb 22, 2024
Sirtuins (SIRTs) tau lees paub lub neej ntev regulators hauv cov qauv kab mob. Txij li thaum thawj qhov kev tshawb pom tias SIRTs txuas ntxiv lub neej nyob rau hauv nematodes thiab yoov, tus cwj pwm ntawm cov proteins no tau ua rau muaj kev nkag siab txog lawv lub luag haujlwm raws li qhov muag pom kev sib txuas cov haujlwm metabolic rau oxidative. SIRTs ua lub luag haujlwm tseem ceeb hauv cov txheej txheem lom neeg tseem ceeb hauv lub raum kev loj hlob thiab kev ua haujlwm ntawm lub cev, suav nrog mitochondrial metabolism, oxidative stress, autophagy, kho DNA, thiab o. Tsis tas li ntawd, kev hloov pauv hauv SIRT kev ua ub no cuam tshuam nrog pathophysiology thiab kev loj hlob ntawm cov kab mob raum mob thiab mob ntev, nrog rau mob raum raug mob, mob ntshav qab zib nephropathy, mob raum, kab mob polycystic raum, kab mob autoimmune, thiab lub raum laus.
Nyem rau Cistanche rau mob raum
Cov teebmeem renoprotective ntawm SIRTs hauv cov kab mob no ua rau lawv cov hom phiaj kho mob zoo dua. Ob peb SIRT-activating compounds tau pom muaj txiaj ntsig zoo hauv cov qauv kab mob raum; Txawm li cas los xij, kev tshawb fawb ntxiv rau cov tshiab SIRT-targeting protein cov tswv yim los kho thiab / lossis tiv thaiv kab mob raum thiab ua kom muaj sia nyob hauv tib neeg yog xav tau.
Cov ntsiab lus tseem ceeb
Sirtuins (SIRTs) pib nyiam kev tshawb fawb zoo heev vim lawv lub luag haujlwm hauv kev tswj hwm lub neej hauv kev sim ua qauv; Txawm li cas los xij, tam sim no lawv feem ntau lees paub tias yog tus tsav tsheb ntawm kev laus noj qab haus huv.
SIRTs tswj cov txheej txheem tseem ceeb hauv cellular homeostasis, suav nrog cov metabolism, kev ua haujlwm mitochondrial, oxidative stress, DNA kho, apoptosis, senescence, thiab o.
SIRTs ua lub luag haujlwm tseem ceeb hauv lub raum kev loj hlob thiab lub cev nqaij daim tawv vim lawv qhov dav cytoprotective cuam tshuam rau lub raum tshwj xeeb thiab txawv hom cell, suav nrog podocytes thiab tubular cells.
SIRT kev hloov pauv tau raug txheeb xyuas tias yog tus tsav tsheb ntawm ntau yam kab mob raum hauv tib neeg thiab cov qauv kev sim, suav nrog mob raum raug mob, mob raum, thiab mob raum mob ntshav qab zib.
Kev txheeb xyuas ntawm sirtuin-active compounds yog lub hom phiaj tseem ceeb hauv thaj teb; Qee cov tshuaj sirtuin-activating tau pom tias yuav txhim kho SIRT kev ua haujlwm thiab muab lub raum tiv thaiv hauv cov qauv kev sim, tab sis ob peb tau nkag mus rau kev sim tshuaj.
Txhawm rau kom paub txog qhov muaj peev xwm ntawm cov kev cuam tshuam no hauv kev kho thiab tiv thaiv kab mob raum thiab ua rau tib neeg muaj kev noj qab haus huv, SIRT-targeting compounds tshiab nrog kev txhim kho potency thiab bioavailability yog xav tau.
kev taw qhia
Sirtuins (SIRTs) yog ib chav kawm ntawm evolutionarily conserved histone deacetylases (HDACs) uas nws cov dej num yuav tsum tau nicotinamide adenine dinucleotide (NAD+). Txij li thaum lawv qhov kev tshawb pom thawj zaug 30 xyoo dhau los, cov proteins ntawm tsev neeg no tau ua qhov tseem ceeb ntawm kev tshawb fawb dav dav, feem ntau vim yog lawv lub luag haujlwm hauv kev tswj hwm lub neej hauv cov qauv kab mob, suav nrog Saccharomyces cerevisiae, Caenorhabditis elegans, thiab Melanogaster ya. Tsis tas li ntawd, tsawg kawg yog ib qho SIRT, SIRT6, cuam tshuam nrog kev ua neej nyob hauv cov txiv neej nas. Txawm li cas los xij, thawj zaug kev txaus siab rau SIRTs raws li kev ua neej ntev ntawm cov proteins waned raws li cov kev tshawb fawb tom ntej tau tawm tsam qhov kev xav tias SIRTs cuam tshuam txog kev ua neej nyob hauv nematodes thiab kab.
Raws li kev sib cav txog lub luag haujlwm ntawm SIRTs nyob rau hauv lub neej ntev nthuav dav, ntau cov kev tshawb fawb tau pom tias SIRTs yog tus kws kho mob tseem ceeb hauv kev ntsuas cov kev ntxhov siab ntau dhau hauv cov kab mob metabolically, suav nrog ob lub raum. Cov kev tshawb pom no ua rau lub tswv yim tias SIRTs yog cov tsav tsheb tseem ceeb ntawm kev laus noj qab haus huv es tsis yog cov tswj hwm kev ua neej ntev. Piv txwv li, overexpression ntawm lub hlwb tshwj xeeb Sirt1 nyob rau hauv nas ho ncua kev laus. Hauv qhov sib piv, kev tshem tawm Sirt3 lossis Sirt6 ua rau muaj kev laus ntxov ntxov ntsig txog lub cev puas tsuaj hauv cov nas.
Kab lus no tshuaj xyuas lub luag haujlwm ntawm SIRTs hauv kev tswj hwm lub raum kev loj hlob thiab cov txheej txheem physiological xws li cellular zog homeostasis, kev ua haujlwm antioxidant, thiab kho DNA. Peb kuj tham txog cov txheej txheem molecular hauv qab lub luag haujlwm tseem ceeb ntawm SIRTs hauv cov kab mob ntawm cov kab mob hauv lub raum mob thiab mob ntev, tsom mus rau feem ntau kawm SIRTs, SIRT1, SIRT3, thiab SIRT6. Thaum kawg, peb hais txog lub peev xwm ntawm SIRTs raws li cov hom phiaj kho mob los tiv thaiv tib neeg lub raum kab mob thiab lub raum laus thiab qhov xav tau los txheeb xyuas cov tswv yim tshiab los txhawb cov proteins no.
mammal sirtuins
Tag nrho cov SIRTs muaj ib tug catalytic core ntawm kwv yees li 270 seem thiab N- thiab C-terminal fragments uas txawv nyob rau hauv ntev thiab sib lawv liag. Mammalian SIRTs ua nyob rau hauv cov cellular compartments, qhov uas lawv qhia tshwj xeeb rau ntau yam ntawm acyl protein substrates.
Tag nrho SIRTs tshwj tsis yog SIRT4 nthuav tawm cov haujlwm deacetylase los ntawm ob kauj ruam sib law liag; NAD + yog thawj zaug cleaved rau hauv nicotinamide (NAM) thiab ADP-ribose thiab tom qab ntawd ua tus txais rau lysine acetyl pawg ntawm cov hom phiaj protein. Tsim O-acetyl-ADP-ribose (2′-O-malonyl-ADP-ribose, 2′-OAADPr). SIRT5 muaj cov haujlwm acylase ntxiv thiab hloov cov pab pawg malonyl lossis succinyl hauv lysine ntawm lub hom phiaj protein rau ADP ribose, raws li tsim 2′-O-malonyl-ADP ribose (2′-O- malonyl-ADP-ribose, 2′-OMADP ) thiab 2′-O-succinyl-ADP-ribose (2′-O-succinyl-ADP-ribose, 2′-OSADP). SIRT4 muaj ADP-ribosyltransferase kev ua haujlwm thiab txhawb nqa kev hloov pauv ntawm ADP-ribose los ntawm NAD + mus rau lysine ntawm lub hom phiaj protein los tsim NAM. Lub xeev metabolic ntawm lub cell txiav txim siab NAD + qib thiab SIRT enzyme kev ua.
nuclear sirtuins
Peb SIRT1, SIRT6, thiab SIRT7 yog nyob rau hauv lub nucleus. Qhov feem ntau kawm txog nuclear SIRT yog SIRT1, uas deacetylates histones ntawm H4 lysine 16 (H4K16) thiab H3 lysine 9 (H3K9), yog li tswj cov noob transcription. Cytoplasmic localization ntawm SIRT1 kuj tau tshaj tawm. Cytoplasmic SIRT1 yog txuam nrog deacetylation ntawm non-histone proteins, suav nrog DNA-binding transcription yam thiab lawv co-regulatory molecules, ntxiv nthuav lub luag hauj lwm lom ntawm cov protein no.
SIRT6 ncaj qha deacetylates histones H3K9 thiab H3K56 thiab ua lub luag haujlwm tseem ceeb hauv kev tswj hwm genome stability thiab telomere muaj nuj nqi. SIRT7 lub hom phiaj tseem tsis tau pom dua. SIRT7 feem ntau yog nyob rau hauv lub nucleolus, muaj feem xyuam rau RNA polymerase I mechanism, thiab yuav tsum tau rau ribosomal DNA transcription. Lub pas dej cytoplasmic ntawm SIRT7 uas tuaj yeem ua lub luag haujlwm hauv kev rov ua dua tshiab kuj tau txheeb xyuas.
Cytoplasmic sirtuins
Cytosolic SIRT2 cuam tshuam nrog microtubules thiab deacetylates lysine 40 ntawm -microtubules. Nyob rau hauv feem ntau somatic hlwb, acetylated tubulin yuav tsum tau rau mitosis thiab localizes rau organelles koom nyob rau hauv ntau theem ntawm lub cell voj voog. SIRT2 lub peev xwm los txwv tubulin acetylation plays lub luag haujlwm hauv kev tswj hwm ntawm mitosis. Hauv particular, SIRT2 yog upregulated nyob rau hauv lub G2 / M theem thiab inhibited nyob rau hauv lub M theem los txhawb mitotic tawm hauv lub cell voj voog. Kev ua tsis tiav ntawm SIRT2 inhibition prolongs M theem.
mitochondrial sirtuins
SIRT3 tau piav qhia tias yog tus tswj hwm tus tswj hwm thoob ntiaj teb mitochondrial protein deacetylation, raws li kev tshawb pom thawj zaug uas SIRT3-cov nas tsis muaj peev xwm muaj qib mitochondrial protein acetylation ntau dua, whereas Sirt4- thiab Sirt5- cov nas tsis muaj zog muaj qis mitochondrial protein acetylation qib. SIRT3 kuj pom nyob rau hauv lub nucleus, qhov twg nws lub hom phiaj histones H3 thiab H4. Thaum lub sij hawm cov lus teb kev ntxhov siab, nuclear SIRT3 tuaj yeem hloov mus rau mitochondria, qhia tias nws yuav yog tus tswj hwm tseem ceeb ntawm kev tiv thaiv kev tiv thaiv kev puas tsuaj ntawm tes.
Hauv mitochondria, SIRT4 feem ntau yog ADP-ribosylase thiab, tsis zoo li lwm yam SIRTs, yog inactivated nyob rau hauv cov kev txwv caloric. SIRT5 yog thawj zaug tau txheeb xyuas tias yog mitochondrial deacetylase, tab sis muaj arginine (Arg105) thiab tyrosine (Tyr102) residues hauv nws qhov chaw nquag tshaj tawm cov dej num ntxiv declonase thiab succinate.
Cistanche kho mob raum li cas?
Cistancheyog ib hom tshuaj suav tshuaj ntsuab siv rau ntau pua xyoo los kho ntau yam mob, suav nrograumkab mob. Nws yog muab los ntawm qhuav stems ntawmCistanchedeserticola, ib tsob nroj nyob rau hauv cov suab puam ntawm Tuam Tshoj thiab Mongolia. Lub ntsiab active Cheebtsam ntawm cistanche yogphenylethanoidglycosides, echinacoside cov tshuaj, thiabacteoside, uas tau pom tias muaj txiaj ntsig zoo rau lub raum kev noj qab haus huv.
Kab mob raum, tseem hu ua kab mob raum, yog ib yam mob uas lub raum ua haujlwm tsis zoo. Qhov no tuaj yeem ua rau muaj cov khoom pov tseg thiab cov co toxins hauv lub cev, ua rau muaj ntau yam tsos mob thiab teeb meem. Cistanche tuaj yeem pab kho mob raum ase los ntawm ntau lub tswv yim.
Ua ntej, cistanche tau pom tias muaj cov nyhuv diuretic, txhais tau tias nws tuaj yeem ua rau cov zis ntau ntxiv thiab pab tshem tawm cov khoom pov tseg ntawm lub cev. Qhov no tuaj yeem pab txo lub nra ntawm lub raum thiab tiv thaiv kev tsim cov co toxins. Los ntawm kev txhawb nqa diuresis, cistanche kuj tseem tuaj yeem pab txo qis ntshav siab, ib qho teeb meem ntawm cov kab mob raum.
Ntxiv mus, cistanche tau pom tias muaj cov teebmeem antioxidant. Kev ntxhov siab oxidative, tshwm sim los ntawm qhov tsis sib xws ntawm kev tsim cov dawb radicals thiab lub cev tiv thaiv antioxidant, ua lub luag haujlwm tseem ceeb hauv kev mob raum. ies pab neutralize dawb radicals thiab txo Oxidative kev nyuaj siab, yog li tiv thaiv lub raum los ntawm kev puas tsuaj. Cov phenylethanoid glycosides pom hauv cistanche tau tshwj xeeb hauv kev tshem tawm cov dawb radicals thiab inhibiting lipid peroxidation.
Tsis tas li ntawd, cistanche tau pom tias muaj cov nyhuv anti-inflammatory. Kev mob yog lwm yam tseem ceeb hauv kev loj hlob thiab kev loj hlob ntawm cov kab mob raum. Cistanche's anti-inflammatory zog pab txo cov zus tau tej cov pro-inflammatory cytokines thiab inhibit qhov ua kom o yuav tsum tau txoj kev, yog li alleviating o nyob rau hauv lub raum.
Tsis tas li ntawd, cistanche tau pom tias muaj cov teebmeem immunomodulatory. Hauv kab mob raum, lub cev tiv thaiv kab mob tuaj yeem ua rau tsis zoo, ua rau muaj kev mob ntau dhau thiab cov ntaub so ntswg puas. Cistanche pab tswj lub cev tiv thaiv kab mob los ntawm kev hloov kho kev tsim khoom thiab kev ua haujlwm ntawm lub cev tiv thaiv kab mob, xws li T hlwb thiab macrophages. Txoj cai tiv thaiv kab mob no pab txo qhov mob thiab tiv thaiv kev puas tsuaj ntxiv rau lub raum.
Ntxiv mus, cistanche tau pom los txhim kho lub raum kev ua haujlwm los ntawm kev txhawb nqa kev tsim kho ntawm lub raum hlab nrog cov hlwb. Lub raum tubular epithelial hlwb ua lub luag haujlwm tseem ceeb hauv kev pom thiab rov nqus cov khoom pov tseg thiab electrolytes. Hauv kab mob raum, cov hlwb no tuaj yeem raug puas tsuaj, ua rau lub raum ua haujlwm puas. Cistanche lub peev xwm los txhawb kev tsim kho ntawm cov hlwb no pab kho lub raum kom zoo thiab txhim kho lub raum tag nrho.
Ntxiv nrog rau cov kev cuam tshuam ncaj qha rau lub raum, cistanche tau pom tias muaj txiaj ntsig zoo rau lwm yam kabmob thiab lub cev hauv lub cev. Txoj hauv kev zoo rau kev noj qab haus huv no tseem ceeb tshwj xeeb hauv cov kab mob raum, vim tias tus mob feem ntau cuam tshuam rau ntau lub cev thiab lub cev. che tau pom tias muaj kev tiv thaiv rau lub siab, lub plawv, thiab cov hlab ntsha, uas feem ntau cuam tshuam los ntawm kab mob raum. Los ntawm kev txhawb nqa kev noj qab haus huv ntawm cov kabmob no, cistanche pab txhim kho lub raum tag nrho thiab tiv thaiv kev mob ntxiv.
Hauv kev xaus, cistanche yog cov tshuaj suav tshuaj ntsuab siv rau ntau pua xyoo los kho mob raum. Nws cov active Cheebtsam muaj diuretic, antioxidant, anti-inflammatory, immunomodulatory, thiab regenerative teebmeem, uas pab txhim kho lub raum ua haujlwm thiab tiv thaiv ob lub raum los ntawm kev puas tsuaj ntxiv. , cistanche muaj txiaj ntsig zoo rau lwm yam kabmob thiab lub cev, ua rau nws txoj hauv kev zoo rau kev kho mob raum.
