转位SIRT6促进糖解重编程以加剧糖尿病血管病变
Kemiao Pang1, Jiayi Huang1, Shiwu Zhang1
1Department of Cardiology, Department of Pathophysiology, Key Laboratory of Myocardial Ischemia, Ministry of Education, Second Affiliated Hospital of Harbin Medical University, China.
Redox biology
|June 28, 2025
概括
糖尿病血管病症涉及血管功能障碍. 这项研究揭示了细胞质SIRT6促进了血管光滑肌细胞的病态糖解,推动了疾病的进展. 向SIRT6可能提供新的治疗策略.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 心血管研究研究心血管研究
背景情况:
- 糖尿病血管病,是2型糖尿病 (T2DM) 的并发症,源于血管功能障碍,代谢变化和氧化应激.
- 核SIRT6通过激素脱乙烯化来调节代谢和心血管平衡,但其在T2DM中的细胞质作用尚不清楚.
研究的目的:
- 调查SIRT6在糖尿病血管改造期间促进病态糖解的以前未知的细胞质功能.
- 阐明细胞质中SIRT6积累的分子机制及其在糖尿病血管病变中的作用.
主要方法:
- 在血管光滑肌细胞 (VSMCs) 中,研究了由Importin 13 (IPO13) 介导的SIRT6转移到细胞质.
- 鉴定出酶3 (ENO3) 作为下游标,与细胞质SIRT6.6相互作用.
- 评估了外源硫化 (H2S) 对SIRT6 S-硫化,SIRT6-ENO3相互作用,糖解和VSMC增殖的影响.
主要成果:
- 由IPO13促进的SIRT6的细胞质积累与糖尿病患者的VSMC增殖相关.
- 细胞质SIRT6与ENO3相互作用并脱乙,增强酸 (PEP) 水平并驱动糖解.
- 外源H2S恢复了SIRT6的S-硫化,抑制了SIRT6-ENO3的相互作用,抑制了葡萄糖分解,并减少了VSMC的过度增殖.
结论:
- 通过SIRT6-ENO3通路确定了SIRT6在促进糖尿病血管病的病态糖解和血管重塑中的新型细胞质作用.
- 证明了通过调节SIRT6 S-硫化来向SIRT6-ENO3相互作用,为糖尿病血管病变提供了潜在的治疗途径.
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