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Mechanisms of xenon‐ and isoflurane‐induced preconditioning – a potential link to the cytoskeleton via the MAPKAPK‐2/HSP27 pathway
Author(s) -
Weber Nina C,
Toma Octavian,
Wolter Jessica I,
Wirthle Nicole M,
Schlack Wolfgang,
Preckel Benedikt
Publication year - 2005
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0706324
Subject(s) - isoflurane , hsp27 , calphostin c , p38 mitogen activated protein kinases , protein kinase a , anesthetic , protein kinase c , phosphorylation , cytoskeleton , chemistry , actin cytoskeleton , microbiology and biotechnology , mapk/erk pathway , heat shock protein , biology , biochemistry , medicine , anesthesia , cell , hsp70 , organic chemistry , gene
We previously demonstrated that the anesthetic gas xenon exerts cardioprotection by preconditioning in vivo via activation of protein kinase C (PKC)‐ ɛ and p38 mitogen‐activated protein kinase (MAPK). P38 MAPK interacts with the actin cytoskeleton via the MAPK‐activated protein kinase‐2 (MAPKAPK‐2) and heat‐shock protein 27 (HSP27). The present study further elucidated the underlying molecular mechanism of xenon‐induced preconditioning (Xe‐PC) by focusing on a potential link of xenon to the cytoskeleton. Anesthetized rats received either xenon (Xe‐PC, n =6) or the volatile anesthetic isoflurane (Iso‐PC, n =6) during three 5‐min periods interspersed with two 5‐min and one final 10‐min washout period. Control rats ( n =6) remained untreated for 45 min. Additional rats were either pretreated with the PKC inhibitor Calphostin C (0.1 mg kg −1 ) or with the p38 MAPK inhibitor SB203580 (1 mg kg −1 ) with and without anesthetic preconditioning (each, n =6). Hearts were excised for immunohistochemistry of F‐actin fibers and phosphorylated HSP27. Phosphorylation of MAPKAPK‐2 and HSP27 were assessed by Western blot. HSP27 and actin colocalization were investigated by co‐immunoprecipitation. Xe‐PC induced phosphorylation of MAPKAPK‐2 (control 1.0±0.2 vs Xe‐PC 1.6±0.1, P <0.05) and HSP27 (control 5.0±0.5 vs Xe‐PC 9.8±1.0, P <0.001). Both effects were blocked by Calphostin C and SB203580. Xe‐PC enhanced translocation of HSP27 to the particulate fraction and increased F‐actin polymerization. F‐actin and pHSP27 were colocalized after Xe‐PC. Xe‐PC activates MAPKAPK‐2 and HSP27 downstream of PKC and p38 MAPK. These data link Xe‐PC to the cytoskeleton, revealing new insights into the mechanisms of Xe‐PC in vivo .British Journal of Pharmacology (2005) 146 , 445–455. doi: 10.1038/sj.bjp.0706324