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.