Oscillatory shear stress-mediated aberrant O-GlcNAc SIRT3 accelerates glycocalyx inflammatory injury via LKB1/p47phox/Hyal2 signaling

被引：2

作者：

Zhang, Lei ^{[2
]}

Li, Jiajia ^{[1
]}

Chen, Jun ^{[2
]}

Lei, Jin ^{[2
]}

Yuan, Zhiyi ^{[2
]}

Zhang, Jun ^{[3
]}

Liu, Zhaohong ^{[2
]}

Yu, Chao ^{[2
]}

Ma, Limei ^{[2
]}

机构：

[1] Hechuan Dist Peoples Hosp, Chongqing, Peoples R China

[2] Chongqing Med Univ, Coll Pharm, Chongqing Key Res Lab Drug Metab, Chongqing, Peoples R China

[3] Chongqing Med Univ, Inst Life Sci, Chongqing, Peoples R China

来源：

CELLULAR SIGNALLING | 2023年 / 109卷

基金：

中国国家自然科学基金;

关键词：

Vascular endothelial glycocalyx; O-GlcNAcylation; SIRT3; Oscillatory shear stress; LKB1; p47phox; Hyal2; pathway; ENDOTHELIAL-CELL DYSFUNCTION; BETA-N-ACETYLGLUCOSAMINE; PROTEIN; GLCNACYLATION; ACTIVATION; HYPERACETYLATION; IMPAIRMENT; STABILITY; SYNTHASE;

D O I：

10.1016/j.cellsig.2023.110790

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Glycocalyx coating on endothelial surface layer helps to sense shear forces and maintain endothelial function. However, the underlying mechanism of endothelial glycocalyx degradation upon disordered shear stress stimulation is not fully understood. SIRT3, a major NAD+-dependent protein deacetylases, is required for protein stability during vascular homeostasis and partly involved in atherosclerotic process. While few studies showed that SIRT3 is responsible for endothelial glycocalyx homeostasis under shear stress, the underlying mechanisms remain largely unknown. Here, we demonstrated that oscillatory shear stress (OSS) induces glycocalyx injury by activating LKB1/p47phox/Hyal2 axis both in vivo and in vitro. And O-GlcNAc modification served to prolong SIRT3 deacetylase activity and stabilized p47/Hyal2 complex. OSS could decrease SIRT3 O-GlcNAcylation to activate LKB1, further accelerated endothelial glycocalyx injury in inflammatory microenvironment. SIRT3Ser329 mutation or inhibition of SIRT3 O-GlcNAcylation strongly promoted glycocalyx degradation. On the contrary, overexpression of SIRT3 reverse glycocalyx damage upon OSS treatment. Together, our findings indicated that targeting O-GlcNAcylation of SIRT3 could prevent and/or treat diseases whereby glycocalyx injured.

引用

页数：13