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Molecular and Cellular Biochemistry

, Volume 278, Issue 1–2, pp 39–51 | Cite as

Ceramide activates a mitochondrial p38 mitogen-activated protein kinase: A potential mechanism for loss of mitochondrial transmembrane potential and apoptosis

  • Jennifer Y. Kong
  • Shaun S. Klassen
  • Simon W. RabkinEmail author
Article

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)

Key Word

ceramide cardiomyocytes heart p38 MAPK mitochondria apoptosis 

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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Jennifer Y. Kong
    • 1
  • Shaun S. Klassen
    • 1
  • Simon W. Rabkin
    • 1
    Email author
  1. 1.Department of Medicine (Cardiology)University of British ColumbiaVancouverCanada

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