Cardiolipin activates MAP kinases during premature senescence in normal human fibroblasts

Abstract

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.

Cyclophosphamide induces premature senescence in normal human fibroblasts by activating MAP kinases

“…Activation of this program can be triggered by multiple afferent signaling pathways, and its completion also involves induction of multiple genes that are now under extensive investigation (Minagawa et al 2004(Minagawa et al , 2005. Recently, various methods of inducing senescence have been shown to activate a small subset of signaling pathways that ultimately coverage upon activation of the MAP kinase cascades (Arivazhagan and Ayusawa 2007). The MAP kinase pathways are complex and are yet to be fully understood.…”