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An α‐Tubulin‐Dependent Mechanism for Isoflurane‐Mediated Cardioprotection
Author(s) -
Procknow Jesse D,
Baotic Ines,
Weihrauch Dorothee,
Pratt Phillip,
Kersten Judy
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1085.9
Subject(s) - enos , cardioprotection , nitric oxide , isoflurane , chemistry , acetylation , compartmentalization (fire protection) , tubulin , microtubule , microbiology and biotechnology , nitric oxide synthase , endothelial nos , pharmacology , ischemia , caveolin , biochemistry , caveolae , signal transduction , biology , medicine , enzyme , organic chemistry , gene
Volatile anesthetics such as isoflurane (ISO) protect the myocardium from ischemia and reperfusion injury. Nitric oxide (NO) signaling has been identified as a critical component of anesthetic‐mediated cardioprotection. As endothelial nitric oxide synthase (eNOS) can be regulated by ISO and the acetylation state of α‐tubulin, we wished to elucidate the mechanism responsible for the cardioprotective effects of ISO. We used human coronary artery endothelial cells to investigate the effect of ISO on acetylated α‐tubulin expression and the role acetylated α‐tubulin plays in the compartmentalization of eNOS and caveolin‐1 (Cav‐1). After ISO exposure, expression of acetylated α‐tubulin was increased with immunofluorescence (IF) labeling (657.52 ± 7.01 vs 576.08 ± 9.13 u) and Western blotting compared to control cells. IF labeling of phosphorylated (P‐) eNOS was also increased after ISO treatment (658.8 ± 7.64 vs 567.2 ± 7.26 u). Additionally, ISO stimulated the translocation of eNOS and Cav‐1 to caveolar fractions as assessed by sucrose gradient fractionation. ISO‐treated cells increased NO production compared to control cells (565.0 ± 90.02 vs 316.9 ± 37.3 pmol/mg) as previously demonstrated. These data suggest that the cardioprotective effects of ISO work through a tubulin‐dependent mechanism that increases trafficking of eNOS and Cav‐1 to caveolar fractions, increasing P‐eNOS and therefore NO production.