SIRT1 Antagonizes Oxidative Stress in Diabetic Vascular Complication

Frontiers in Endocrinology

Teng Meng²  Weifeng Qin⁴  Baohua Liu⁴ 

[1] Molecular Biology, School of Basic Medical Sciences, Shenzhen University, Shenzhen, China;;Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Department of Biochemistry &Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, China;Shenzhen Key Laboratory for Systemic Aging and Intervention, National Engineering Research Center for Biotechnology (Shenzhen), Medical Research Center, Shenzhen University Health Science Center, Shenzhen, China;

关键词: SIRT1;    oxidative stress;    diabetic vascular complications;    adenosine-monophosphate-activated protein kinase;    mechanistic target of rapamycin;    microRNAs;   

DOI  :  10.3389/fendo.2020.568861

来源: DOAJ

【 摘 要 】

Diabetic mellitus (DM) is a significant public health concern worldwide with an increased incidence of morbidity and mortality, which is particularly due to the diabetic vascular complications. Several pivotal underlying mechanisms are associated with vascular complications, including hyperglycemia, mitochondrial dysfunction, inflammation, and most importantly, oxidative stress. Oxidative stress triggers defective angiogenesis, activates pro-inflammatory pathways and causes long-lasting epigenetic changes to facilitate the development of vascular complications. Therefore, therapeutic interventions targeting oxidative stress are promising to manage diabetic vascular complications. Sirtuin1 (SIRT1), a class III histone deacetylase belonging to the sirtuin family, plays critical roles in regulating metabolism and ageing-related pathological conditions, such as vascular diseases. Growing evidence has indicated that SIRT1 acts as a sensing regulator in response to oxidative stress and attenuates vascular dysfunction via cooperating with adenosine-monophosphate-activated protein kinase (AMPK) to activate antioxidant signals through various downstream effectors, including peroxisome proliferator-activated receptor-gamma co-activator 1 (PGC-1α), forkhead transcription factors (FOXOs), and peroxisome proliferative-activated receptor α (PPARα). In addition, SIRT1 interacts with hydrogen sulfide (H2S), regulates NADPH oxidase, endothelial NO synthase, and mechanistic target of rapamycin (mTOR) to suppress oxidative stress. Furthermore, mRNA expression of sirt1 is affected by microRNAs in DM. In the current review, we summarize recent advances illustrating the importance of SIRT1 in antagonizing oxidative stress. We also discuss whether modulation of SIRT1 can serve as a therapeutic strategy to treat diabetic vascular complications.

【 授权许可】

Unknown