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NMNH, kahi moʻolelo a me ka mana NAD precursor

2024-08-27 10:00:38

ʻO Nicotinamide adenine dinucleotide (NAD) homeostasis e hoʻomau mau ʻia ma muli o ka hoʻohaʻahaʻa ʻia e nā enzymes hilinaʻi NAD. ʻO ka hoʻohui ʻana i ka NAD me nā NAD precursors nicotinamide mononucleotide (NMN) a me nicotinamide riboside (NR) hiki ke hoʻēmi i kēia ʻano like ʻole. Ua hōʻike kekahi poʻe noiʻi i ke ʻano synthesis o kahi ʻano hōʻemi o NMN,NMNH, a ua ʻike i kēia mole ma ke ʻano he NAD precursor hou no ka manawa mua, a ua hōʻoia ʻia ʻoi aku ka maikaʻi o ka NMNH ma mua o NMN a me NR i ka hoʻonui ʻana i nā pae NAD a hiki ke hōʻemi i ka nui o ka tubule renal. Ua pōʻino nā pūnaewele epithelial a ua wikiwiki ko lākou hoʻoponopono ʻana. Ua paʻi ʻia nā hopena ma "The FASEB Journal".

Enzymatic synthesis o NMNH: Hoʻohana ʻia ka hana kiʻekiʻe o NAD pyrophosphatase mai Escherichia coli (EcNADD) e hoʻokaʻawale i ka NADH i NMNH a me AMP.

NMNHhoʻonui maikaʻi i ka ʻike NAD:

I mea e hōʻoia ai inā hiki i ka NMNH ke hoʻonui maikaʻi i ka ʻike NAD, ua hoʻokomo ʻia nā ʻano ʻokoʻa like ʻole o NMN a me NMNH i loko o nā puʻupuʻu ate o AML12 mice. Ua hōʻike ʻia nā hopena i kēlā me kēia neʻe ʻana, hoʻonui ka NMNH i ka pae NAD ma mua o NMN. I ka manawa like, ua hoʻonui nui ʻia nā pae NAD i loko o nā minuke 15 me ka hoʻohana ʻana i ka NMNH ma ke ʻano he precursor, e hōʻike ana he ʻoi aku ka wikiwiki o ka NMNH ma mua o NMN; a hoʻohālikelike ʻia me NMN, hoʻonui ʻo NMNH i nā pae NAD e 1.3-2.4 mau manawa. ʻO ka hiki ke hoʻonui i nā pae NAD mai 5.2 mau manawa a 37 mau manawa e hōʻoiaʻiʻo ai ʻo NMNH kahi precursor maikaʻi loa no ka synthesis NAD.

No ka hoʻohālikelike i nā hopena o NMNH a me NMN, ua hoʻopiʻi nā mea noiʻi i ka PBS a me 250 mg / kg o NMN aNMNHi loko o nā ʻiole C57BL/6N, kēlā me kēia, a laila alakaʻi ʻia i ka hōʻike koko sequential. Ua hōʻike nā hopena ua hoʻonui nui ʻo NMNH i nā pae NAD i loko o ke koko, i kahi ʻoi aku ka nui ma mua o NMN. Ua ana ʻia ʻo NAD ma nā ʻiʻo i hōʻiliʻili ʻia ma o ke ʻano pōʻaiapili enzyme. Ua hōʻike ʻia nā hopena ua hoʻonui ʻo NMNH i nā pae NAD i nā ʻāpana like ʻole, a ʻoi aku ka hopena ma mua o ka NMN. Ua ʻike ʻia ka hopena ma ke ake a me nā puʻupaʻa, me ka piʻi ʻana o ke akepaʻa ma mua o 5 mau manawa a ʻoi aku ka piʻi ʻana o nā puʻupaʻa ma mua o 5 mau manawa. 2 manawa.

NMNHpale i nā pūnana epithelial tubular renal mai ka pōʻino:

I loko o ka puʻupaʻa, ʻoi aku ka maʻalahi o nā cell epithelial tubular proximal i ka hōʻeha ischemic no ka mea pili pono ia i ka metabolism ikehu a kau i ke koʻikoʻi nui i ka NAD metabolism i ka epithelium. ʻO nā hemahema i nā ala metabolic a me ka hiki ke hoʻemi i ka hoʻoponopono ʻana i nā kaʻina hana epithelial i pōʻino e predispose i ka maʻi maʻi. Hiki i ka hoʻonui ʻana i nā pae NAD ma ka injecting exogenous NMNH hoʻihoʻi maikaʻi i nā cell epithelial i hōʻino ʻia? ʻO ka hoʻoponopono ʻana i ka NMNH ma lalo o nā kūlana normoxic i hoʻonui i ka ʻikepili NAD 5-fold, ʻoiai ma ka ʻike like, ʻoi aku ka haʻahaʻa o ka hopena o NMN ma mua o ka NMNH. Ua hoʻonui nui ka NAD precursors i ka ʻike NAD i nā cell epithelial tubular renal ma lalo o nā kūlana hypoxic, ʻoi aku ma luna o nā kūlana normoxic. Ua ʻike ʻia kahi kūlana like i loko o nā hepatocytes moʻomeheu, kahi i hoʻokō ʻia ai ka NMNH i ka hoʻonui ʻana i nā metabolites pili i ka NAD i kahi ʻoi aku ka nui ma mua o ka NMN.

Ua hoʻonui ʻia ka NMNH i ka wā reoxygenation, a ua ʻike ʻia ka hōʻike o ka hōʻailona hōʻeha tubular renal KIM-1. ʻO ka reoxygenation ma TEC i hoʻonui nui i ka ʻōlelo KIM-1, i emi nui ma hope o ka mālama ʻana i ka NMNH, e hōʻike ana i ka hoʻokeleNMNHhiki ke hōʻemi maikaʻi a hoʻemi nui i ka pōʻino o nā pūnaewele epithelial tubular renal i ka wā hypoxia a me reoxygenation.

Alanui OlaNMNHpana maoli

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NMNH, kahi moʻolelo a me ka mana NAD precursor