Involvement of p38 MAP kinase in burn-induced degradation of membrane phospholipids and upregulation of cPLA2 in cardiac myocytes.

Abstract

This study was aimed to evaluate the role of p38 mitogen-activated protein (MAP) kinase in the degradation of membrane phospholipids and the regulation of cytosolic phospholipase A2 (cPLA2) in cardiac myocytes after burn trauma. In an in vivo study, rats were randomized into four groups: (1) sham-burn group, (2) burn group (40% total body surface area full-thickness burn), (3) burn + SB203580 group, and (4) burn + vehicle group. The rats from each group were killed at varying times after burn to examine the p38 MAP kinase activation (by means of Western blot analysis and immunohistochemical assay), the expression of cPLA2 (by means of reverse transcriptase polymerase chain reaction), the level of cardiac membrane phospholipids, and the level of the remaining creatine kinase-MB (CK-MB) isoenzyme in the heart. These studies showed that burn resulted in a significant decrease in the level of cardiac membrane phospholipids from 3 to 24 h after burn, which was paralleled with a persistent activation of p38 MAP kinase and an increased expression of cPLA2 in the heart. SB203580, a selective inhibitor of p38 MAP kinase, inhibited the activation of cardiac p38 MAP kinase, suppressed the burn-induced upregulation of cPLA2 and the increased PLA2 activity, and prevented burn-induced decrease in the levels of the cardiac membrane phospholipids and the remaining creatine kinase-MB isoenzyme. In addition, the in vitro treatment of cardiac myocytes with SB203580 also abolished the upregulation of cPLA2 and the disturbance of phospholipid homeostasis elicited by hypoxia and burn serum challenge. Taken together, these results have demonstrated for the first time that p38 MAP kinase is involved in burn-induced membrane phospholipids degradation in cardiac myocytes, at least in part through the regulation of cPLA2.

• Authors: Jia-Ping Zhang, Wan-Yi Liang, Zhong-Hua Luo, Zong-Cheng Yang, Hsiao-Chang Chan, Yue-Sheng Huang
• Journal: Shock (Augusta, Ga.) (Shock) Vol. 28 Issue 1 Pg. 86-93 (Jul 2007) ISSN: 1073-2322 [Print] United States
• PMID: 17483741 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Primers
• Imidazoles
• Membrane Lipids
• Phospholipids
• Protein Kinase Inhibitors
• Pyridines
• RNA, Messenger
• p38 Mitogen-Activated Protein Kinases
• Phospholipases A
• Phospholipases A2
• SB 203580

Topics

• Active Transport, Cell Nucleus
• Animals
• Base Sequence
• Burns (genetics, metabolism)
• DNA Primers (genetics)
• Enzyme Activation
• Imidazoles (pharmacology)
• In Vitro Techniques
• Membrane Lipids (metabolism)
• Myocytes, Cardiac (drug effects, metabolism)
• Phospholipases A (genetics, metabolism)
• Phospholipases A2
• Phospholipids (metabolism)
• Protein Kinase Inhibitors (pharmacology)
• Pyridines (pharmacology)
• RNA, Messenger (genetics, metabolism)
• Rats
• Rats, Wistar
• Up-Regulation
• p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)