CD38 inhibition by apigenin ameliorates mitochondrial oxidative stress through restoration of the intracellular NAD+/NADH ratio and Sirt3 activity in renal tubular cells in diabetic rats.
Aging (Albany NY)
; 12(12): 11325-11336, 2020 06 07.
Article
en En
| MEDLINE
| ID: mdl-32507768
ABSTRACT
Mitochondrial oxidative stress is a significant contributor to the pathogenesis of diabetic kidney disease (DKD). We previously showed that mitochondrial oxidative stress in the kidneys of Zucker diabetic fatty rats is associated with a decreased intracellular NAD+/NADH ratio and NAD+-dependent deacetylase Sirt3 activity, and increased expression of the NAD+-degrading enzyme CD38. In this study, we used a CD38 inhibitor, apigenin, to investigate the role of CD38 in DKD. Apigenin significantly reduced renal injuries, including tubulointerstitial fibrosis, tubular cell damage, and pro-inflammatory gene expression in diabetic rats. In addition, apigenin down-regulated CD38 expression, and increased the intracellular NAD+/NADH ratio and Sirt3-mediated mitochondrial antioxidative enzyme activity in the kidneys of diabetic rats. In vitro, inhibition of CD38 activity by apigenin or CD38 knockdown increased the NAD+/NADH ratio and Sirt3 activity in renal proximal tubular HK-2 cells cultured under high-glucose conditions. Together, these results demonstrate that by inhibiting the Sirt3 activity and increasing mitochondrial oxidative stress in renal tubular cells, CD38 plays a crucial role in the pathogenesis of DKD.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Glicoproteínas de Membrana
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Sirtuinas
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ADP-Ribosil Ciclasa
/
Diabetes Mellitus Tipo 2
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Nefropatías Diabéticas
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ADP-Ribosil Ciclasa 1
/
Sirtuina 3
Tipo de estudio:
Etiology_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Aging (Albany NY)
Asunto de la revista:
GERIATRIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Japón