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    NMNH, inoveli uye ine simba NAD precursor

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    NMNH, inoveli uye ine simba NAD precursor

    2024-08-27 10:00:38


    Nicotinamide adenine dinucleotide (NAD) homeostasis inoramba ichikanganiswa nekuda kwekuderedzwa nema enzymes anoenderana neNAD. Kuwedzera NAD neNAD precursors nicotinamide mononucleotide (NMN) uye nicotinamide riboside (NR) inogona kuderedza kusaenzana uku. Vamwe vatsvakurudzi vakashuma nzira yekubatanidza yeNMN yakaderedzwa,NMNH, uye yakaratidza iyi molecule sechinhu chitsva cheNAD kekutanga, uye yakasimbisa kuti NMNH inoshanda zvakanyanya kupfuura NMN neNR mukuwedzera NAD mazinga uye inogona kuderedza renal tubule size. Epithelial masero akakuvadzwa uye kugadzirisa kwavo kunokurumidza. Mhedzisiro yacho yakaburitswa mu "The FASEB Journal".

    Enzymatic synthesis yeNMNH: Basa repamusoro reNAD ​​pyrophosphatase kubva kuEscherichia coli (EcNADD) rinoshandiswa kubatanidza NADH muNMNH uye AMP.

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    NMNHzvinobudirira zvinowedzera NAD zvemukati:
    Kuti uone kana NMNH ichikwanisa kuwedzera NAD zvirimo, zvakasiyana-siyana zveNMN neNMNH zvakaiswa mumasero echiropa eAML12 mbeva. Mhedzisiro yakaratidza kuti pane yega yega, NMNH yakawedzera iyo NAD level yakakwira kupfuura NMN. Panguva imwecheteyo, mazinga eNAD akawedzera zvakanyanya mukati memaminitsi e15 achishandisa NMNH sechinhu chinotangira, zvichiratidza kuti NMNH inokurumidza kukurumidza kupfuura NMN; uye ichienzaniswa neNMN, NMNH yakawedzera mazinga eNAD ne1.3-2.4 nguva. Kukwanisa kuwedzera mazinga eNAD kubva pa5.2 nguva kusvika makumi matatu nenomwe nguva zvinoratidza kuti NMNH inonyanyo shanda yeNAD synthesis.
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    Kuti uenzanise mhedzisiro yeNMNH neNMN, vaongorori vakabaya PBS uye 250 mg/kg yeNMN uyeNMNHmuC57BL/6N mbeva, zvichiteerana, ndokuzoita sequential sampling yeropa. Zvigumisiro zvakaratidza kuti NMNH yakawedzera zvakanyanya mazinga eNAD muropa, kusvika pamwero mukuru kudarika NMN. NAD yakayerwa pamatishu akaunganidzwa kuburikidza neiyo enzyme cycle nzira. Mhedzisiro yacho yakaratidza kuti NMNH yakawedzera mazinga eNAD mumhando dzakasiyana siyana, uye mhedzisiro yacho yaive yakakwira kupfuura yeNMN. Yakanga iine simba rakanyatsojeka pachiropa neitsvo, nechiropa chinowedzera kanopfuura ka5 uye itsvo dzichiwedzera kanopfuura ka5. 2 nguva.

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    NMNHinodzivirira renal tubular epithelial masero kubva mukukuvara:
    Mukati meitsvo, iyo proximal tubular epithelial masero anonyanya kukanganisa kukuvara kweischemic nokuti inobata zvakananga simba remetabolism uye inoisa kushushikana kukuru paNAD metabolism muepithelium. Kusaenzana kwemetabolism nzira uye kugona kuderedzwa kugadzirisa zvakakanganisika epithelial maitiro anotungamira kune chirwere cheitsvo. Unogona here kuwedzera mazinga eNAD nekubaya exogenous NMNH zvinobudirira kudzoreredza akakuvadzwa epithelial maseru? Kutungamirirwa kweNMNH pasi pemamiriro ezvinhu e-normoxic akawedzera NAD zvinyorwa 5-fold, nepo panguva imwecheteyo, mhedzisiro yeNMN yakanga yakaderera kupfuura iyo yeNMNH. Ose maviri NAD precursors akawedzera zvakanyanya NAD zvemukati mune renal tubular epithelial masero pasi pe hypoxic mamiriro, kunyangwe pamusoro penormoxic mamiriro. Mamiriro ezvinhu akafanana akaonekwa muhutano hwehepatocytes, uko kutungamirirwa kweNMNH kwakakonzerawo kuwedzera kweNAD-yakabatana metabolites kusvika pamwero mukuru kupfuura NMN.
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    NMNH yakawedzerwa panguva ye reoxygenation phase, uye kutaura kwe renal tubular kukuvara marker KIM-1 yakaonekwa. Reoxygenation muTEC yakakonzera kuwedzera kwakanyanya kweKIM-1 kutaura, iyo yakaderera zvakanyanya mushure mekurapa kweNMNH, zvichiratidza kuti kutonga kweNMNHinogona zvinobudirira uye zvakanyanya kuderedza kukuvadzwa kwerenal tubular epithelial masero panguva ye hypoxia uye reoxygenation.

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