Protection against endotoxic shock as a consequence of reduced nitrosative stress in MLCK210-null mice.
This study investigated the consequences of deletion of the long isoform of myosin light chain kinase (MLCK210) on the cardiovascular changes induced by the bacterial endotoxin lipopolysaccharide (LPS) and cecal ligation puncture using MLCK210-/- mice. Here, we provide evidence that deletion of MLCK210 enhanced survival after intraperitoneal injection of LPS or cecal ligation puncture. LPS-induced vascular hyporeactivity to vasoconstrictor agents was completely prevented in aorta from MLCK210-/- mice. This was associated with a decreased up-regulation of nuclear facor-kappaB expression and activity, inducible nitric-oxide synthase, and level of oxidative stress in the vascular media. Furthermore, LPS-induced increase of nitric oxide production in the circulation and tissues (including heart, liver, and lung) that was correlated with an increased expression of inducible nitric-oxide synthase was also reduced in MLCK210-/- mice. These data demonstrate a role for MLCK210 in endotoxin shock injury associated with oxidative and nitrosative stresses and vascular hyporeactivity.
Ralay Ranaivo
Hantamalala
H
UMR INSERM 771-CNRS 7034, Faculté de Pharmacie, Illkirch, France.
Carusio
Nunzia
N
Wangensteen
Rosemary
R
Ohlmann
Patrick
P
Loichot
Cecile
C
Tesse
Angela
A
Chalupsky
Karel
K
Lobysheva
Irina
I
Haiech
Jacques
J
Watterson
D Martin
DM
Andriantsitohaina
Ramaroson
R
D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D017353:Gene Deletion; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009219:Myosin-Light-Chain Kinase / Q000172:deficiency / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D012772:Shock, Septic / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D015854:Up-Regulation / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects / Q000235:genetics
D008070:Lipopolysaccharides; D016328:NF-kappa B; C440499:lipopolysaccharide, Escherichia coli O111 B4; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D009219:Myosin-Light-Chain Kinase