Contrasting actions of prolonged mitogen-activated protein kinase activation on cell survival |
| |
Authors: | Badrian Bahareh Casey Tammy M Lai May C Rakoczy P Elizabeth Arthur Peter G Bogoyevitch Marie A |
| |
Institution: | Biochemistry and Molecular Biology, University of Western Australia (UWA), and Lions Eye Institute, Crawley, WA 6009, Australia. |
| |
Abstract: | Activation of the ERK mitogen-activated protein kinase pathway has been implicated in pro-survival and cellular protective mechanisms, so that chronic ERK activation may be a useful therapeutic strategy. Here, we further explored the consequences of prolonged ERK activation following expression of constitutively active form of MEK, MEK-EE, in cardiac myocytes. We confirmed that chronic MEK-EE overexpression halved myocyte death following glucose deprivation, but surprisingly this was not associated with preserved intracellular ATP levels. Whilst activities of a number of antioxidant enzymes were not altered upon MEK-EE expression, paradoxically Cu/Zn superoxide dismutase activity was almost halved upon MEK-EE expression. When we then exposed myocytes to the superoxide generator menadione, we observed significantly higher death of MEK-EE expressing myocytes. Pre-incubation with U0126 inhibited menadione-induced death. Our results are the first to show that MEK-ERK signalling can act to increase or decrease cell survival, the outcome depending on the form of stress stimulus encountered. |
| |
Keywords: | Mitogen-activated protein kinase Cell death Energy stress ATP levels Superoxide dismutase |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|