| First Author | Rudyk O | Year | 2013 |
| Journal | Proc Natl Acad Sci U S A | Volume | 110 |
| Issue | 24 | Pages | 9909-13 |
| PubMed ID | 23716652 | Mgi Jnum | J:197401 |
| Mgi Id | MGI:5492268 | Doi | 10.1073/pnas.1301026110 |
| Citation | Rudyk O, et al. (2013) Protein kinase G oxidation is a major cause of injury during sepsis. Proc Natl Acad Sci U S A 110(24):9909-13 |
| abstractText | 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 Ialpha), 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 Ialpha oxidative activation in injury is supported by oxidation-resistant Cys42Ser PKG Ialpha knock-in mice being markedly protected from these clinical indices of injury during sepsis. We conclude that oxidative activation of PKG Ialpha is a key mediator of hypotension and consequential organ injury during sepsis. |
