Protection against endotoxic shock as a consequence of reduced nitrosative stress in MLCK210-null mice

Hantamalala Ralay Ranaivo, Nunzia Carusio, Rosemary Wangensteen, Patrick Ohlmann, Cecile Loichot, Angela Tesse, Karel Chalupsky, Irina Lobysheva, Jacques Haiech, D. Martin Watterson, Ramaroson Andriantsitohaina*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

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-κB 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.

Original languageEnglish (US)
Pages (from-to)439-446
Number of pages8
JournalAmerican Journal of Pathology
Volume170
Issue number2
DOIs
StatePublished - Feb 2007

Funding

Supported by Fonds de Recherche Hoechst Marion Roussel (grant GIP-HMR2): Exploration Fonctionnelle et Analyse Globale de l'Expression des Gènes, and Fondo Europeo de Desarrollo Regional no. 8891. H.R.R. was supported by the Bourse BDI of CNRS.

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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