01.
NMNHbyongera selile NAD + na NADH urwego. Abashakashatsi bagereranije ingaruka za NMN na NMNH mu kongera urwego rwa selile NAD +. Umuti hamwe na NMNH (100 μM) wongereye urwego rwa selile NAD + inshuro 5 muri selile HepG2, mugihe 100 μM NMN yiyongereyeho gato urwego rwa NAD +. Usibye ingirabuzimafatizo za HepG2, abashakashatsi bemeje kandi ko NMNH yazamuye NAD + mu ngirabuzimafatizo za ES-2 na selile 3T3-L1, ari zo ngirabuzimafatizo zikomoka ku ntanga ngabo na selile fibroblast ikomoka ku mbeba. Abashakashatsi basanze kandi NMNH yongereye selile NAD + selile muri selile 786-O mugihe- kandi biterwa nubushakashatsi. Abashakashatsi bapimye NADH bakoresheje sprometrike rusange basanga urwego rwa NADH mu ngirabuzimafatizo za HepG2 zivuwe na NMNH rwikubye inshuro 2,5 ugereranije n’utugingo tutavuwe kandi twavuwe na NMN, kandi urwego rwa NADH rwaragaragaye no mu tugari twa NMNH twavuwe na 786-O. Twasanze kandi 340 mg / kg Ubuvuzi bwa NMNH bwongereye NADH urwego rwimbeba inshuro 3, mugihe 340 mg / kg NMN ivura yongereye urwego rwa NADH inshuro 1.7.
Igicapo 1.2. NMNH yongera NAD + urwego
Igicapo 3.4. NMNH yongera urwego rwa NMNH
02NMNH ibuza glycolysis na TCA cycle. Ikusanyirizo rya NADH ridindiza glycolysis na TCA cycle. Kugira ngo basuzume uburyo bwo guhindura imikorere ya selile kubuvuzi bwa NMNH, abashakashatsi bakoze isesengura rya metabolomic
NMNH-na NMN ivurwa. Byagaragaye ko kuvura NMNH bitagabanije gusa urwego rwabahuza glycolysis, ahubwo byanagabanije urwego rwabahuza TCA. Ibisubizo byerekana ko kwirundanya kwa NADH byakozwe na NMNH bibuza selile glycolysis na TCA cycle.
Igicapo 5. Kugabanya glycolysis hamwe na TCA cycle hagati
Igicapo 6. Isesengura rya Metabolomics
03.
NMNHibuza gukura kw ingirabuzimafatizo Abashakashatsi bakoze ubushakashatsi ku ngaruka za NMNH ku mikurire y’utugingo basanga ubuvuzi bwa NMNH bwabujije imikurire ya selile HepG2 ku busumbane buri hejuru ya 250 μM. Abashakashatsi basesenguye uruziga rw'utugingo ngengabuzima twa HepG2 bavuwe na mM 1 NMNH cyangwa NMN mu gihe cy'amasaha 12 basanga NMNH yarateje ingirabuzimafatizo, mu gihe NMN nta ngaruka yagize ku ruzinduko rw'akagari. Byongeye kandi, abashakashatsi basanze kandi 500 μM NMNH yahagaritse rwose imikurire ya selile 786-O; 250 μM NMNH irashobora kubuza neza imikurire ya selile muri selile HK-2.
Igicapo 7.8.NMNH ibuza gukura kwingirabuzimafatizo muri vitro
04.
NMNHabashakashatsi bashinzwe umutekano bakoze ubushakashatsi ku kumenya niba dosiye nyinshi za NMNH zitera hepatotoxicity. Kuvura imbeba zabagabo C57BL / 6J hamwe na 50, 100, 500, cyangwa 1000 mg / kg NMNH ukoresheje inshinge za intraperitoneal buri munsi icyumweru cyose byagaragaje ko nta kugabanuka kwa serumu alanine aminotransferase (ALT) hamwe na aminotransferase (AST). Hejuru, byerekana ko NMNH itari hepatotoxic kuri dosiye nyinshi. Byongeye kandi, abashakashatsi basanze kandi ubuvuzi bwa NMNH bwongereye NAD + ibirimo imbeba muburyo butandukanye. Umuti hamwe na mg / kg 1000 NMNH wongereye NAD + urwego rwimbeba inshuro zirenga 10.
Igicapo 10.
NMNHbyongera urwego rwa NAD + mu mwijima wimbeba
Ubushakashatsi bwerekanye ko NMNH ari inyongera ya NAD + -kuzamura kurusha NMN haba muri vitro ndetse no muri vivo; wongeyeho, NMNH yongera igabanuka rya NAD (NADH) murwego rwimbeba nimbeba. Isesengura rya Metabolomic ryerekanye ko NMNH ibuza glycolysis na TCA cycle. Ubushakashatsi bwa vitro bwerekana ko NMNH itera ingirabuzimafatizo kandi ikabuza gukura kwakagari. Ufatiye hamwe, ubu bushakashatsi bwerekana ko NMNH niyongera imbaraga za NAD + kandi ikabuza glycolysis, ukwezi kwa TCA, no gukura kwakagari.
Izina ry'igishinwa rya NMNH "ryagabanijwe β-nicotinamide mononucleotide", ni bwo buryo bwagabanijwe bwa NMN kandi ni ifu y'umuhondo amorphous. Inzira ya molekulari: C11H17N2O8P Uburemere bwa molekuline: 336.23g / molCAS No.: 108347-85-9 Ibitabo byubushakashatsi biheruka kwerekana byerekana ko NMNH yongerera NAD + urwego rwihuse kandi mukwiyongera cyane, ugereranije inshuro 5 nubwa NMN
Inzira y'UbuzimaNMNHishoti ryukuri
