Bogoyevitch, M. A., Gillespie-Brown, J. , Ketterman, A. J., Fuller, S. J., Ben-Levy, R., Ashworth, A., Marshall, C. J. and Sugden, P. H. (1996) Stimulation of the stress-activated mitogen-activated protein kinase subfamilies in perfused heart: p38/RK mitogen-activated protein kinases and c-Jun N-terminal kinases are activated by ischemia/reperfusion. Circulation Research, 79(2), pp. 162-173. (doi: 10.1161/01.res.79.2.162)
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Publisher's URL: http://dx.doi.org/10.1161/01.res.79.2.162
Abstract
It has recently been recognized that cellular stresses activate certain members of the mitogen-activated protein kinase (MAPK) superfamily. One role of these “stress-activated” MAPKs is to increase the transactivating activity of the transcription factors c-Jun, Elk1, and ATF2. These findings may be particularly relevant to hearts that have been exposed to pathological stresses. Using the isolated perfused rat heart, we show that global ischemia does not activate the 42- and 44-kD extracellular signal–regulated (protein) kinase (ERK) subfamily of MAPKs but rather stimulates a 38-kD activator of MAPK-activated protein kinase-2 (MAPKAPK2). This activation is maintained during reperfusion. The molecular characteristics of this protein kinase suggest that it is a member of the p38/reactivating kinase (RK) group of stress-activated MAPKs. In contrast, stress-activated MAPKs of the c-Jun N-terminal kinase (JNK/SAPKs) subfamily are not activated by ischemia alone but are activated by reperfusion following ischemia. Furthermore, transfection of ventricular myocytes with activated protein kinases (MEKK1 and SEK1) that may be involved in the upstream activation of JNK/SAPKs induces increases in myocyte size and transcriptional changes typical of the hypertrophic response. We speculate that activation of multiple parallel MAPK pathways may be important in the responses of hearts to cellular stresses.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Brown, Dr Judith |
| Authors: | Bogoyevitch, M. A., Gillespie-Brown, J., Ketterman, A. J., Fuller, S. J., Ben-Levy, R., Ashworth, A., Marshall, C. J., and Sugden, P. H. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Public Health |
| Journal Name: | Circulation Research |
| Publisher: | Lippincott Williams & Wilkins |
| ISSN: | 0009-7330 |
| ISSN (Online): | 1524-4571 |
| Related URLs: |
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