NAD(P)H: quinone oxidoreductase 1 attenuates oxidative stress and apoptosis by regulating Sirt1 in diabetic nephropathy.
J Transl Med
; 20(1): 44, 2022 01 28.
Article
em En
| MEDLINE
| ID: mdl-35090502
BACKGROUND: Diabetic nephropathy (DN) is one of the main complications of diabetes, and oxidative stress plays an important role in its progression. NAD(P)H: quinone oxidoreductase 1 (NQO1) protects cells from oxidative stress and toxic quinone damage. In the present study, we aimed to investigate the protective effects and underlying mechanisms of NQO1 on diabetes-induced renal tubular epithelial cell oxidative stress and apoptosis. METHODS: In vivo, the kidneys of db/db mice, which are a type 2 diabetes model, were infected with adeno-associated virus to induce NQO1 overexpression. In vitro, human renal tubular epithelial cells (HK-2 cells) were transfected with NQO1 pcDNA3.1(+) and cultured in high glucose (HG). Gene and protein expression was assessed by quantitative real-time PCR, western blotting, immunofluorescence analysis, and immunohistochemical staining. Reactive oxygen species (ROS) were examined by MitoSox red and flow cytometry. TUNEL assays were used to measure apoptosis. RESULT: In vivo, NQO1 overexpression reduced the urinary albumin/creatinine ratio (UACR) and blood urea nitrogen (BUN) level in db/db mice. Our results revealed that NQO1 overexpression could significantly increase the ratio of NAD+/NADH and silencing information regulator 1 (Sirt1) expression and block tubular oxidative stress and apoptosis in diabetic kidneys. In vitro, NQO1 overexpression reduced the generation of ROS, NADPH oxidase 1 (Nox1) and Nox4, the Bax/Bcl-2 ratio and the expression of Cleaved Caspase-3 and increased NAD+/NADH levels and Sirt1 expression in HK-2 cells under HG conditions. However, these effects were reversed by the Sirt1 inhibitor EX527. CONCLUSIONS: All these data suggest that NQO1 has a protective effect against oxidative stress and apoptosis in DN, which may be mediated by the regulation of Sirt1 through increasing intracellular NAD+/NADH levels. Therefore, NQO1 may be a new therapeutic target for DN.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
NAD(P)H Desidrogenase (Quinona)
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Diabetes Mellitus Tipo 2
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Nefropatias Diabéticas
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Sirtuína 1
Limite:
Animals
Idioma:
En
Revista:
J Transl Med
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China