Document Detail

Mechanisms of xenon- and isoflurane-induced preconditioning - a potential link to the cytoskeleton via the MAPKAPK-2/HSP27 pathway.
MedLine Citation:
PMID:  16086037     Owner:  NLM     Status:  MEDLINE    
We previously demonstrated that the anesthetic gas xenon exerts cardioprotection by preconditioning in vivo via activation of protein kinase C (PKC)-epsilon 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.
Nina C Weber; Octavian Toma; Jessica I Wolter; Nicole M Wirthle; Wolfgang Schlack; Benedikt Preckel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  146     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2005 Oct 
Date Detail:
Created Date:  2005-10-03     Completed Date:  2006-04-25     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  445-55     Citation Subset:  IM    
Department of Anesthesiology, University Hospital of Düsseldorf, Germany.
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MeSH Terms
Anesthetics, Inhalation / pharmacology*
Cytoskeleton / drug effects,  metabolism
HSP27 Heat-Shock Proteins
Heat-Shock Proteins / metabolism*
Intracellular Signaling Peptides and Proteins
Ischemic Preconditioning, Myocardial*
Isoflurane / pharmacology
Myocardium / metabolism
Neoplasm Proteins / metabolism*
Phosphorylation / drug effects
Protein-Serine-Threonine Kinases / metabolism*
Rats, Wistar
Xenon / pharmacology*
p38 Mitogen-Activated Protein Kinases / metabolism
Reg. No./Substance:
0/Anesthetics, Inhalation; 0/HSP27 Heat-Shock Proteins; 0/Heat-Shock Proteins; 0/Hspb1 protein, rat; 0/Intracellular Signaling Peptides and Proteins; 0/Neoplasm Proteins; 26675-46-7/Isoflurane; 7440-63-3/Xenon; EC 2.7.1.-/MAP-kinase-activated kinase 2; EC Kinases; EC Mitogen-Activated Protein Kinases

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