Protein kinase G oxidation is a major cause of injury during sepsis

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 wildtype mice induced oxidative activation of cGMP-dependent protein kinase 1 alpha (PKG lα), which...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2013-06, Vol.110 (24), p.9909-9913
Main Authors: Rudyk, Olena, Phinikaridou, Alkystis, Prysyazhna, Oleksandra, Burgoyne, Joseph R., Botnar, René M., Eaton, Philip
Format: Article
Language:English
Subjects:
Amino Acid Substitution
Animals
antihypertensive effect
Antioxidants
Biological Sciences
Blood plasma
Blood pressure
Blood vessels
cardiac output
cGMP-dependent protein kinase
Cyclic GMP-Dependent Protein Kinase Type I - genetics
Cyclic GMP-Dependent Protein Kinase Type I - metabolism
Disulfides
Enzyme Activation - genetics
Hypotension
Hypotension - enzymology
Hypotension - genetics
Hypotension - physiopathology
Immunoblotting
inflammation
Kinases
L-Lactate Dehydrogenase - blood
Mice
Mice, Inbred C57BL
Mice, Transgenic
Multiple Organ Failure - enzymology
Multiple Organ Failure - genetics
Multiple Organ Failure - physiopathology
Oxidation
Oxidation-Reduction
Oxidative stress
permeability
Physical trauma
Rodents
Sepsis
sepsis (infection)
Sepsis - enzymology
Sepsis - genetics
Sepsis - physiopathology
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Summary: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 wildtype mice induced oxidative activation of cGMP-dependent protein kinase 1 alpha (PKG lα), 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 lα oxidative activation in injury is supported by oxidation-resistant Cys42Ser PKG lα knock-in mice being markedly protected from these clinical indices of injury during sepsis. We conclude that oxidative activation of PKG lα is a key mediator of hypotension and consequential organ injury during sepsis.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1301026110