Cardiolipin activates MAP kinases during premature senescence in normal human fibroblasts.
Lipids are major structural components of cellular membranes and regulate various signaling pathways as a mediator of the signals or a source of new signals. Our earlier studies show that cardiolipin very sensitively induces premature senescence in normal human fibroblasts. To understand a molecular basis for the action of cardiolipin, we tested whether the mitogen-activated protein (MAP) kinase cascades have a role in the above phenomenon. As expected, cardiolipin activated phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinases (JNK), and p38 map kinase (p38) of the MAP kinase family as in replicatively senesced cells. These results suggest that cardiolipin uses signaling pathways similar to those in replicative senescence to lead to premature senescence.
Arivazhagan
Palaniyappan
P
Department of Biochemistry, Kihara Institute for Biological Research, Yokohama City University, Maioka-cho 641-12, Yokohama, 244-0813, Japan.
Ayusawa
Dai
D
D002308:Cardiolipins / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D016922:Cellular Senescence; D004789:Enzyme Activation; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008168:Lung / Q000196:embryology / Q000201:enzymology / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D010766:Phosphorylation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D002308:Cardiolipins; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases