期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2013
卷号：110
期号：24
页码：9909-9913
DOI：10.1073/pnas.1301026110
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Sepsis is a common life-threatening clinical syndrome involving complications as a result of severe infection. A cardinal feature of sepsis is inflammation that results in oxidative stress. Sepsis in wild-type mice induced oxidative activation of cGMP-dependent protein kinase 1 alpha (PKG I), which increased blood vessel dilation and permeability, and also lowered cardiac output. These responses are typical features of sepsis and their combined effect is a lowering of blood pressure. This hypotension, a hallmark of sepsis, resulted in underperfusion of end organs, resulting in their damage. A central role for PKG I oxidative activation in injury is supported by oxidation-resistant Cys42Ser PKG I knock-in mice being markedly protected from these clinical indices of injury during sepsis. We conclude that oxidative activation of PKG I is a key mediator of hypotension and consequential organ injury during sepsis.
