Reactive oxygen species precede the epsilon isoform of protein kinase C in the anesthetic preconditioning signaling cascade. Anesthesiology 2003 Aug;99(2):421-8
Date
07/29/2003Pubmed ID
12883415DOI
10.1097/00000542-200308000-00024Scopus ID
2-s2.0-0042845907 (requires institutional sign-in at Scopus site) 101 CitationsAbstract
BACKGROUND: Protein kinase C (PKC) and reactive oxygen species (ROS) are known to have a role in anesthetic preconditioning (APC). Cardiac preconditioning by triggers other than volatile anesthetics, such as opioids or brief ischemia, is known to be isoform selective, but the isoform required for APC is not known. The authors aimed to identify the PKC isoform that is involved in APC and to elucidate the relative positions of PKC activation and ROS formation in the APC signaling cascade.
METHODS: Isolated guinea pig hearts were subjected to 30 min of ischemia and 120 min of reperfusion. Before ischemia, hearts were either untreated or treated with sevoflurane (APC) in the absence or presence of the nonspecific PKC inhibitor chelerythrine, the PKC-delta inhibitor PP101, or the PKC-epsilon inhibitor PP149. Spectrofluorometry and the fluorescent probes dihydroethidium were used to measure intracellular ROS, and effluent dityrosine as used to measure extracellular ROS release.
RESULTS: Previous sevoflurane exposure protected the heart against ischemia-reperfusion injury, as previously described. Chelerythrine or PP149 abolished protection, but PP101 did not. ROS formation was observed during sevoflurane exposure and was not altered by any of the PKC inhibitors.
CONCLUSIONS: APC is mediated by PKC-epsilon but not by PKC-delta. Furthermore, PKC activation probably occurs downstream of ROS generation in the APC signaling cascade.
Author List
Novalija E, Kevin LG, Camara AK, Bosnjak ZJ, Kampine JP, Stowe DFAuthors
Amadou K. Camara PhD Professor in the Anesthesiology department at Medical College of WisconsinDavid F. Stowe MD, PhD Professor in the Anesthesiology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnestheticsAnesthetics, Inhalation
Animals
Blood Pressure
Coronary Circulation
Electrophysiology
Enzyme Activation
Ethidium
Fluorescent Dyes
Guinea Pigs
In Vitro Techniques
Ischemic Preconditioning, Myocardial
Isoenzymes
Methyl Ethers
Myocardial Contraction
Myocardial Infarction
Myocardium
Protein Kinase C
Protein Kinase C-delta
Protein Kinase C-epsilon
Reactive Oxygen Species
Signal Transduction
Tyrosine
Ventricular Function, Left