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I-NMNH, inoveli nesandulela se-NAD esinamandla

Isizinda samandla esiphansi emhlabeni omelene nokuguga——NMNH

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I-NMNH, inoveli nesandulela se-NAD esinamandla

2024-08-27 10:00:38

I-Nicotinamide adenine dinucleotide (NAD) i-homeostasis iqhubeka ifakwa engcupheni ngenxa yokonakala kwama-enzyme ancike ku-NAD. Ukwengeza i-NAD nge-NAD precursors i-nicotinamide mononucleotide (NMN) kanye ne-nicotinamide riboside (NR) kunganciphisa lokhu kungalingani. Abanye abacwaningi babike indlela yokuhlanganisa yefomu elincishisiwe le-NMN,I-NMNH, futhi yahlonza le molecule njengesandulela esisha se-NAD okokuqala ngqa, futhi yaqinisekisa ukuthi i-NMNH iphumelela kakhulu kune-NMN ne-NR ekwandiseni amazinga e-NAD futhi inganciphisa usayizi weshubhu lezinso. Amaseli e-Epithelial awonakele futhi ukulungiswa kwawo kuyashesha. Imiphumela yashicilelwa ku-"The FASEB Journal".

I-Enzymatic synthesis ye-NMNH: Umsebenzi ophezulu we-NAD pyrophosphatase kusuka ku-Escherichia coli (EcNADD) usetshenziselwa ukuhlukanisa i-NADH ibe yi-NMNH ne-AMP.

I-NMNHkukhulisa ngempumelelo okuqukethwe kwe-NAD:

Ukuze kuqinisekiswe ukuthi i-NMNH ingakwazi yini ukukhulisa okuqukethwe kwe-NAD ngokuphumelelayo, ukugxilisa okuhlukile kwe-NMN ne-NMNH kwajovwa kumaseli esibindi samagundane e-AML12. Imiphumela ibonise ukuthi ekugxiliseni ngakunye, i-NMNH yandisa izinga le-NAD ngaphezu kwe-NMN. Ngesikhathi esifanayo, amazinga e-NAD anda kakhulu phakathi kwemizuzu ye-15 esebenzisa i-NMNH njengesandulela, okufakazela ukuthi i-NMNH iyisandulela esisheshayo kune-NMN; futhi uma kuqhathaniswa ne-NMN, i-NMNH inyuse amazinga e-NAD ngezikhathi ze-1.3-2.4. Ukwazi ukukhulisa amazinga e-NAD ukusuka ezikhathini ze-5.2 ukuya ezikhathini ezingama-37 kufakazela ukuthi i-NMNH iyisandulela esisebenza kahle kakhulu sokuhlanganiswa kwe-NAD.

Ukuze uqhathanise imiphumela ye-NMNH ne-NMN, abacwaningi bajova i-PBS kanye ne-250 mg/kg ye-NMN kanyeI-NMNHkumagundane e-C57BL/6N, ngokulandelana, bese kwenziwa amasampula egazi alandelanayo. Imiphumela yabonisa ukuthi i-NMNH yandisa kakhulu amazinga e-NAD egazini, ngezinga elikhulu kakhulu kune-NMN. I-NAD ikalwa ezicutshini eziqoqiwe ngokusebenzisa indlela yomjikelezo we-enzyme. Imiphumela yabonisa ukuthi i-NMNH yandisa amazinga e-NAD ezicutshini ezihlukahlukene, futhi umphumela wawuphakeme kunalowo we-NMN. Ibe nomthelela osobala kakhulu esibindini nasezinso, isibindi sanda izikhathi ezingaphezu kwezingu-5 futhi izinso zanda izikhathi ezingaphezu kwezingu-5. 2 izikhathi.

I-NMNHivikela amaseli e-renal tubular epithelial ekulimaleni:

Ngaphakathi kwezinso, amangqamuzana e-epithelial e-proximal tubular asengozini enkulu yokulimala kwe-ischemic ngoba athinta ngokuqondile amandla e-metabolism futhi abeka ukucindezeleka okukhulu ku-NAD metabolism ku-epithelium. Ukungalingani ezindleleni ze-metabolic kanye nekhono elincishisiwe lokulungisa izinqubo ze-epithelial ezilimele zibeka phambili isifo sezinso. Ingabe ukwandisa amazinga e-NAD ngokujova i-NMNH yangaphandle kungawabuyisela ngempumelelo amaseli e-epithelial alimele? Ukuphathwa kwe-NMNH ngaphansi kwezimo ze-normoxic kwandisa okuqukethwe kwe-NAD 5-fold, kuyilapho ekugxilweni okufanayo, umphumela we-NMN wawuphansi kakhulu kunalowo we-NMNH. Zombili izandulela ze-NAD zandise kakhulu okuqukethwe kwe-NAD kumaseli e-renal tubular epithelial ngaphansi kwezimo ze-hypoxic, ngisho nangaphezulu kwezimo ze-normoxic. Isimo esifanayo sabonakala kuma-hepatocyte akhulisiwe, lapho ukuphathwa kwe-NMNH nakho kubangele ukwanda kwama-metabolites ahlobene ne-NAD ngezinga elikhulu kakhulu kune-NMN.

I-NMNH yengezwe ngesikhathi sesigaba sokubuyisela umoya-mpilo, futhi ukuvezwa komaka wokulimala kwe-renal tubular KIM-1 kwatholwa. Ukukhishwa kabusha kwe-oksijini ku-TEC kubangele ukwanda okukhulu kwenkulumo ye-KIM-1, eyehla kakhulu ngemva kokwelashwa kwe-NMNH, okubonisa ukuthi ukuphathwaI-NMNHinganciphisa ngempumelelo futhi ngokuphawulekayo ukulimala kwamangqamuzana e-renal tubular epithelial ngesikhathi se-hypoxia kanye ne-reoxygenation.

Indlela yezempiloI-NMNHisibhamu sangempela

Xhumana nathi
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Ukusebenza kanye nendima ye-Artemisinin

Ucwaningo lwakamuva lukhombisa ukuthi alugcini nje ngokuthuthukisa ubuhle kodwa luphinde lulwe nomdlavuza! Udlile namuhla?

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Isayensi edumile ngezithako ezijwayelekile zezimonyo

I-NMNH, inoveli nesandulela se-NAD esinamandla