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Differential MAP kinase activation and Na(+)/H(+) exchanger phosphorylation by H(2)O(2) in rat cardiac myocytes.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Wei, Shi Gao Rothstein, Emily C. Fliegel, Larry Dell'Italia, Louis J. Lucchesi, Pamela A. |
| Copyright Year | 2001 |
| Abstract | Bursts in reactive oxygen species production are important mediators of contractile dysfunction during ischemia-reperfusion injury. Cellular mechanisms that mediate reactive oxygen species-induced changes in cardiac myocyte function have not been fully characterized. In the present study, H(2)O(2) (50 microM) decreased contractility of adult rat ventricular myocytes. H(2)O(2) caused a concentration- and time-dependent activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2), p38, and c-Jun NH(2)-terminal kinase (JNK) mitogen-activated protein (MAP) kinases in adult rat ventricular myocytes. H(2)O(2) (50 microM) caused transient activation of ERK1/2 and p38 MAP kinase that was detected as early as 5 min, was maximal at 20 min (9.6 +/- 1.2- and 9.0 +/- 1.6-fold, respectively, vs. control), and returned to baseline at 60 min. JNK activation occurred more slowly (1.6 +/- 0.2-fold vs. control at 60 min) but was sustained at 3.5 h. The protein kinase C inhibitor chelerythrine completely blocked JNK activation and reduced ERK1/2 and p38 activation. The tyrosine kinase inhibitors genistein and PP-2 blocked JNK, but not ERK1/2 and p38, activation. H(2)O(2)-induced Na(+)/H(+) exchanger phosphorylation was blocked by the MAP kinase kinase inhibitor U-0126 (5 microM). These results demonstrate that H(2)O(2)-induced activation of MAP kinases may contribute to cardiac myocyte dysfunction during ischemia-reperfusion. |
| Starting Page | 25411 |
| Ending Page | 25426 |
| Page Count | 16 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://ajpcell.physiology.org/content/ajpcell/281/5/C1542.full.pdf |
| PubMed reference number | 11600417v1 |
| Volume Number | 281 |
| Issue Number | 5 |
| Journal | American journal of physiology. Cell physiology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Genistein Ischemia Mitogen-Activated Protein Kinases Mitogens Muscle Cells Myocytes, Cardiac Protein Tyrosine Kinase Reactive Oxygen Species Reperfusion Injury Reperfusion Therapy U 0126 chelerythrine eIF-2 Kinase |
| Content Type | Text |
| Resource Type | Article |
