Ceramide activates a mitochondrial p38 mitogen-activated protein kinase: A potential mechanism for loss of mitochondrial transmembrane potential and apoptosis |
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Authors: | Jennifer Y Kong Shaun S Klassen Simon W Rabkin |
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Institution: | (1) Department of Medicine (Cardiology), University of British Columbia, Vancouver, BC, Canada;(2) Room D410, 2733 Heather Street, Vancouver, BC, Canada, V5Z 3J5 |
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Abstract: | This study examined the impact of ceramide, an intracellular mediator of apoptosis, on the mitochondria to test the hypothesis
that ceramide utilized p38 MAPK in the mitochondria to alter mitochondrial potential and induce apoptosis. The capacity of
ceramide to adversely affect mitochondria was demonstrated by the significant loss of mitochondrial potential (ΔΨm), indicated by a J-aggregate fluorescent probe, after embryonic chick cardiomyocytes were treated with the cell permeable
ceramide analogue C2-ceramide. p38 MAPK was identified in the mitochondrial fraction of the cell and p38 MAPK phosphorylation in this mitochondrial
fraction of the cell occurred with ceramide treatment. In addition, SAPK phosphorylation and a decrease in ERK phosphorylation
occurred in whole cell lysates after ceramide treatment. The p38 MAPK inhibitor SB 202190 but not the MEK inhibitor PD 98059
significantly inhibited ceramide-induced apoptosis and loss of ΔΨm. These data suggest that p38 MAPK is present in the mitochondria and its activation by ceramide indicates local signaling
more directly coupled to the mitochondrial pathway in apoptosis. (Mol Cell Biochem 278: 39–51, 2005) |
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Keywords: | ceramide cardiomyocytes heart p38 MAPK mitochondria apoptosis |
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