Publication Date:
2019
Description:
〈p〉Publication date: Available online 28 March 2019〈/p〉
〈p〉〈b〉Source:〈/b〉 Biochemical and Biophysical Research Communications〈/p〉
〈p〉Author(s): Yingli Qiao, Xueli Zhang, Guimei Zhao, Zhiheng Liu, Mingyong Yu, Zheping Fang, Xuehua Li〈/p〉
〈div xml:lang="en"〉
〈h5〉Abstract〈/h5〉
〈div〉〈p〉Although the role of inducible nitric oxide synthase (iNOS) in hepatic ischemia/reperfusion (I/R) injury remains controversial and confusing, with both harmful and beneficial effects in animal studies, the mechanism of these incongruous actions remains unclear. In the current study, we generated bone marrow chimeric mice with hepatocyte-restricted expression of iNOS. Chimeric mice and primary hepatocytes were subjected to I/R or anoxia/reoxygenation stimulation, respectively. The role of iNOS in liver I/R injury and the underlying molecular mechanisms were investigated. Hepatocyte-derived iNOS resulted in hepatoprotection from I/R injury, as well as in vitro experiments. Mechanistically, iNOS upregulates Heat shock protein (HSP) 70 by augmenting heat shock factor 1 (HSF1) binding to the HSP70 gene promoter. Importantly, inhibition of HSP70 partly reversed the iNOS overexpression-mediated hepatoprotection. The present findings demonstrate that hepatocellular iNOS protects from hepatic I/R injury through the HSF1-dependent activation of the HSP70. The upregulation of hepatocellular iNOS may offer a promising strategy for protecting against I/R injury.〈/p〉〈/div〉
〈/div〉
Print ISSN:
0006-291X
Electronic ISSN:
1090-2104
Topics:
Biology
,
Chemistry and Pharmacology
,
Physics
