Nicotinamide Adenine Nucleotide-Lub Qhov Dej Ntawm Cov Hluas Los Tiv Thaiv Oocyte Laus?
Apr 25, 2023
Abstract:Raws li US Special Operations Command (SOCOM), kev sim tshuaj tshiab ntawm ib qhoanti-agingkho qhov ncaujsivcistancheadenine nucleotide yog npaj rau xyoo 2022. Tag nrholub ntiaj teb, kev nrhiav pom ntawm tus ciav ntawm cov tub ntxhais hluas tseem yog lub hom phiaj zoo mus txog, tsis yog ntawm covCov kws tshawb fawb txog kev laus, vim tib neeg xav kom noj qab nyob zoo thiab xav tias hluas thaum laushnub nyoog. Txij li xyoo 1960, cov poj niamncua kev xeeb tubmus kawm qib siab kev kawm thiab kev ua haujlwmtxoj kev tau pab txhawb kom poob qis tag nrho cov poj niam fertility (piv txwv li, tus naj npawb ntawm yugxeeb ntxwv/poj niam). Yog li ntawd, cov poj niam uas muaj hnub nyoog ntau zuj zus nyob ntawmpabkev tsim kho technologies(ART) kom cev xeeb tub. Hauv 2019, Lub Koom Haum Pabcuam Kev Sib Raug ZooTechnology tau tshaj tawm 293,672 cycles rau oocyte retrieval. Qhov kev hloov ntawm cov pej xeem cuam tshuampoj niam lub hnub nyoog muaj lawv thawj tus me nyuam, uas tau nce qhov tseem ceeb. Txawm li cas los xij, lawv cov menyuam yausdaim ntawv qhia pom cov cim ntawm kev laus thaum ntxov hauv lub neej yam tsis muaj kev tiv thaiv zoo. Yog li ntawd,peb yuav nthuav qhia seb NAD ntxiv tuaj yeem pab tiv thaiv kev laus oocyte.
Ntsiab lus:cistancheadenine nucleotide; kev laus; oocyte; NAD plus ; sirtuins
Nyem qhov no kom tau txais cov khoom ntawm Cistanche Extract
1. Taw qhia
Ntau cov ntawv ceeb toom tau hais tias mitochondria yog lub zog hauv lub zes qe menyuam,lub cell loj tshaj plaws hauv tib neeg lub cev [1]. Cov txheej txheem tseem ceeb ntawm kev tsim hluav taws xob hauv oocytes yogoxidative phosphorylation, biochemical txo, thiab oxidizing (redox) txheej txheem thaum lub sij hawmuas reactive oxygen hom (ROS) yog generated raws li ib tug by-product. Rau cov lus tom kawgtxheej txheem, cov saw hlau thauj electron plays lub luag haujlwm tseem ceeb (Daim duab1). Yav dhau losCov kev tshawb fawb tau muab pov thawj muaj zog tias oocyte's redox theem txiav txim siab nws txoj kev loj hlobkev txawj ntse. Hauv ntau cov tshuaj tiv thaiv cellular redox, co-factor cistanche adeninenucleotide (NAD) ua lub luag haujlwm tseem ceeb heev, thiab NAD qib tau raug tshaj tawm kom txo qisnrog hnub nyoog (Daim duab1), uas tau txuas rau kev laus-txog mitochondrial tsis ua haujlwm [1]. Peb lub tswv yim tseem ceeb los tiv thaiv kev laus-txog kev poob qis ntawm NAD tuaj yeem sawv cevqhov ua tau ntawm cov tub ntxhais hluas, tsis yog rau oocyte nkaus xwb, xws li zam / txo qisNAD degradation, supplementing NAD precursors, thiab activating NAD biosyntheticenzymes [1,2]. Lub "dawb radical txoj kev xav ntawm kev laus" [3] hais txog qhov txo qis ntawm oocytestiv thaiv ROS. Interestingly, pov thawj qhia tias cov protein Sirt1 tsis tsuas yog cia siab rauntawm NAD ntxiv raws li cofactor (Daim duab1), tab sis kuj tseem tuaj yeem ua rau lub hnub nyoog cuam tshuam txog kev poob qis hauvoocyte zoo [4]. Tsis ntev los no DNA-methylation thiab epigenetic moos tshawb fawb ntawm oocytes tau qhiatias qee qhov CpG sojntsuam qis qis thiab tsuas yog ib qho kev sojntsuam ntawm SIRT1 yoghypomethylated nrog advancing niam hnub nyoog [5]. Cellular senescence tau npaj rauyog txoj hauv kev lom zem rau ntau yam kab mob ntsig txog kev laus [6]. Senescent hlwbqhia cov yam ntxwv tshwj xeeb xws li kev ntes ntawm kev loj hlob / kev loj hlob, thiab kev sib koom ua ke ntawm senescencesecretory phenotype, uas, ntawm lwm tus, cytokines thiab chemokines yogsecreted, uas ces provoke cov ntaub so ntswg remodeling thiab o [7]. Tseem ceeb, raugRau senescent hlwb yog cov glycolytic thiab mitochondrial oxidative phosphorylation kev ua ub no, thiab muaj qhov nce NAD ntxiv rau cov metabolism hauv tam sim no vim kev qhia siab ntawmcistanchephosphoribosyl-transferase (NAMPT) qhia (Daim duab1A) [7]. Nws tau uatshaj tawm tias qhov tsis muaj NAMPT txo qis qhov muaj NAD ntxiv los ntawm cov xov tooj ntawm tessenescence yog txhawb [8]. Ib txoj kev tshawb fawb tsis ntev los no tau muab pov thawj tias cov hlwb txhawb nqaQhov txo qis ntawm NAD ntxiv thaum lub sijhawm kev laus [9]. Cov kev tshawb pom no qhia tias NAD ntxivyog ib qho tseem ceeb determinant yam tseem ceeb nyob rau hauv cellular senescence txoj kev loj hlob tab sis seb nws qhiatxoj cai yog senescence-associated secretory phenotype txhawb los yog suppressor tej zaumcell-type tshwj xeeb. Dhau li ntawm NAD ntxiv, ob peb lwm yam tshuaj hu ua senolytic, ib txwm muajtshwm sim cov tebchaw xws li Quercetin thiab Curcumin, los yog hluavtaws molecules, tauqhia tias muaj cov nyhuv anti-senescence [10]. Interestingly, ib txoj kev tshawb fawb tsis ntev los no qhia tau tiasQuercetin muaj peev xwm txhim kho qhovhauv vitromaturation ntawm aged murine oocytes [11]. Zoo sib xwsrau NAD ntxiv rau cov nyhuv anti-senescence, polyphenolic compound procyanidin C1, lwm yamtus neeg sawv cev senolytic thiab muaj peev xwm sib tw rau NAD ntxiv, tsis ntev los no tau pom tias inhibit qhovsenescence-associated secretory phenotype thiab kuj txhawb kev loj hlob zoo ntawmporcine oocytes thaum siv hauv vitro [12].
Daim duab 1. Kev cuam tshuam ntawm kev laus ntawm NAD ntxiv rau qib thiab oocyte tus lej, thiab oocyte zoo. (A) Cov kab xiav nyob rau hauv daim duab qhia tau tias maj mam poob ntawm lub pas dej follicular, uas yog kev txhim kho ntau dua tom qab hnub nyoog 35 xyoo ntawm cov poj niam. Cov oocytes nyob rau hauv cov follicles raug ntes nyob rau hauv Prophase ntawm thawj meiotic division, thiab nrog rau kev loj hlob niam muaj hnub nyoog, oocytes 'mitochondria poob lawv cov hauj lwm ntau thiab ntau dua. Yog li ntawd, NAD tsis tshua muaj, oocyte tau txo qhov zoo thiab nyuaj rau cov lus dab neeg tawm tsam ROS. Sirt1 siv NAD ntxiv los ua qhov sib koom ua ke thaum lub sijhawm deacetylation ntawm acetylated proteins. Thaum lub sij hawm no processcistanche yog tsim, uas yog ces rov qab mus rau hauv NAD ntxiv. (B) Lub tswv yim qhia txog kev koom tes ntawm NADH / NAD-hauv cov saw hlau thauj khoom siv hluav taws xob uas thauj cov hluav taws xob raws cov mitochondrial membrane los ntawm ib qho nyuaj (I-IV). Cov ntawv luv: ADP=adenosine diphosphate, ATP=adenosine triphosphate, CoQ coenzyme O.Cwt c cytochrome c, NAM=cistanche, NMN=cistanche mononucleotide, NAMPT{10 }} cistanche phosphoribosyltransferase, NNMAT=cistanche mononucleotide adenylyl-transferase.
Qhov kev tawm tswv yim no tau piav qhia yog tias thiab yuav ua li cas NAD tuaj yeem siv los ua lub hom phiaj kho mob los tiv thaiv oocytes los ntawm kev laus, lossis lwm yam lus, seb NAD tuaj yeem yog tus ciav ntawm cov tub ntxhais hluas los txuas rau poj niam kev yug menyuam.
2. cistanche Adenine Dinucleotide ua Lub Hom Phiaj Kho Mob Zoo los khaws Docyte Zoo los ntawm Kev Laus
Kev khaws cia ntawm oocyte zoo tiv thaiv kev laus yog ib qho ntawm cov haujlwm nyuaj tshaj plaws hauv kev tshawb fawb txog poj niam cev xeeb tub. Raws li lub hnub nyoog ntawm leej niam uas muaj hnub nyoog zuj zus, kev kho mob rau lub hom phiaj no yog qhov xav tau sai. Tsis ntev los no, tau muaj kev saib xyuas ntau ntxiv rau kev kawm txog cov txiaj ntsig ntawm cistanche dinucleotide (NAD ntxiv) rau tib neeg kev noj qab haus huv yog li ntawd, US Special Operations Command tau npaj rau kev sim tshuaj tshiab tshiab ntawm kev kho qhov ncauj los tiv thaiv kev laus rau xyoo 2022. Hauv kev tshawb nrhiav qhov twg nas. siv los ua tus qauv tsiaj, nws tau pom tias kev txhawb nqa NAD ntxiv rau qib los ntawm kev tswj hwm mus sij hawm ntev ntawm nws cov precursor cistanche mononucleotide (NMN), los ntawm cov dej haus tsis zoo, tsis tsuas yog tiv thaiv kev txo qis ntawm zes qe menyuam tab sis kuj rov qab oocyte zoo. thiab fertility muaj nuj nqi hauv cov nas muaj hnub nyoog (13). Hauv particular, tswj cov kev qhia ntawm NAD ntxiv rau cov laus oocytes nyob rau hauv ib theem piv rau cov tub ntxhais hluas oocytes tiv thaiv tsis tau spindle kev ncaj ncees txo oxidative kev nyuaj siab, thiab txhim kho nyob rau hauv yug tus nqi [13]. Ib qho kev tshawb fawb ntau ntxiv tau pom tias muaj kev txaus siab rau kev nkag siab li cas NAD ntxiv tiv thaiv poj niam fertility hauv kev laus. Ib qho kev piav qhia ua tau rau cov lus nug hauv qab no tuaj yeem pom nyob rau hauv kev sib txuas ntawm NAD thiab sirtuins. Sirtuins yog ib tsev neeg ntawm NAD-dependent deacetylases nrog xya tus tswv cuab (SIRT1-7), thiab qee tus ntawm lawv tau uapom tias muaj lub luag haujlwm tswj hwm hauv cov poj niam cev xeeb tub [14–17]. Tiv thaiv covpoob ntawm sirtuins dhau lub sij hawm tau raug pov thawj tias muaj lub luag haujlwm tiv thaiv hauv poj niam fertilitynyob rau hauv ntau yam nrog rau kev tswj kom zoo ntawm oocyte txoj kev loj hlob thiab kev tswj xyuasspindle kev ncaj ncees. Piv txwv li, ntawm lwm tus, SIRT1 tau raug pom zoo los kho qhov teeb meemCov txiaj ntsig zoo ntawm mammalian lub hom phiaj ntawm rapamycin (mTOR) suppression ntawm zes qe menyuamlifespan ntawm sustaining lub primordial follicle pas dej nyob rau hauv nas ovaries [18]. Tsis tas li ntawd, SIRT6knockout oocytes kuj pom muaj qhov tsis xws luag spindle, chromosome misalignment, thiabntau dua aneuploidy tus nqi-cov teebmeem uas yuav yog vim SIRT6-knockdown-inducedhyperacetylation ntawm H4K16 [19,20]. Cov kev tshawb pom no txhawb nqa lub luag haujlwm tiv thaiv ntawmsirtuins thiab qhia tias kev ntxiv ntawm NMN thiab / lossis NAD tuaj yeem yog qhov muaj peev xwmKev kho kom khaws cia zes qe menyuam thiab oocyte zoo hauv cov poj niam uas muaj hnub nyoog siab heev.
3. Cov lus xaus
Qhov tseem ceeb, nws yuav tsum tau piav qhia vim li cas oocytes hnub nyoog ntxov, xyoo ua ntej lwm yamCov tsos mob ntsig txog hnub nyoog tshwm sim, thiab yuav siv NAD li casanti-aging khohauvpoj niam los tsim cov tswv yim yav tom ntej rauncua lub oocyte lifespan thiab zooat ibniam muaj hnub nyoog txaus. Cov kev sim tshuaj tshiab tshaj tawm los ntawm SOCOM tuaj yeem pab tauto taub dab tsi theem ntawm NAD ntxiv muaj nyob rau hauv kev noj qab haus huv laus thiab cov kab mob uas muaj hnub nyoog.Oocytes tsim los ntawm cov tsiaj tuaj yeem sawv cev rau tus qauv nthuav qhia los kawm li cas NAD ntxivpab txhawb kom ncua, tiv thaiv, lossis tej zaum txawm thim rov qab cov cim ntawm kev laus. Kev nce qibthiab kev txhim kho cov cuab yeej pab tu me nyuam thiab biotechnologies yav dhau losPeb caug xyoo tau ua rau nws muaj peev xwm tsim cov qauv los kawm txog kev sib cuam tshuam ntawm ib leegtxoj hauv kev thiab cov txheej txheem hauv oocytes thaum lub sij hawm meiosis. Ua ke, peb cov lus tawm tswv yim tsomlos txhawb cov tswv yim tshawb fawb tshiab ntawm cov ncauj lus nthuav dav no, uas tuaj yeem pab tsim kev tsimcov kev tshawb fawb tshiab thiab cov qauv tsiaj.
Tus sau kev koom tes:PK: conceptualization, sau ntawv, tshuaj xyuas thiab kho, pom kev; W.-HJH:sau thiab kho; DRL: sau ntawv. Txhua tus kws sau ntawv tau nyeem thiab pom zoo rau cov ntawv luam tawm ntawmcov ntawv sau.
Nyiaj txiag:PK tau txais nyiaj txiag sab hauv ntawm Lub Tsev Haujlwm Saib Xyuas Tsiaj Tsiaj thiab Kev Tshawb Fawb Khoom Nojntawm Polish Academy (4/FBW/2020).
Kev lees paub:Cov duab tau tsim nrog BioRender.com, thiab daim duab1B tau yoog los ntawm"Electron Transport Chain", los ntawm BioRender.com (2021). Rov qab los ntawm(mus txog hnub tim 21 Lub Xya Hli 2021).
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 ntaub ntawv
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