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Phospholipase D modulation by ceramide in senescence

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Abstract

Phospholipase D (PLD) has been implicated in mitotic regulation and has been shown to be defective in cells following replicative senescence. We examined the source of changes in PLD activity in senescent human umbilical vein endothelial cells and in human diploid fibroblasts. Using fractionated cell components we found that the cytosolic components were necessary for maximum PLD activation. In comparison to low-passage cells, senescent cells showed a profound lack of PLD activatability. By recombining fractionated components from senescent and low-passage cells, we found that in senescence the membrane component is defective in activating PLD implicating either the PLD enzyme itself or its interaction with PKC and/or ARF. The sphingolipid ceramide has been implicated in mediating senescence. Treatment with ceramide resulted in a decrease in PLD activity, implicating ceramide as the mediator of the inhibition.

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Acknowledgments

This work was supported by a scientist development grant from the American Heart Association and a grant from the Appalachian State University Research Council.

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Authors and Affiliations

  1. Biology Department, Appalachian State University, 572 Rivers St., Boone, NC, 28608-2027, USA

    Lisa M. Webb & Mark E. Venable

  2. Mathematical Sciences Department, Appalachian State University, 121 Bodenheimer Dr, Boone, NC, 28608, USA

    Alan T. Arnholt

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  1. Lisa M. Webb
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  2. Alan T. Arnholt
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  3. Mark E. Venable
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Correspondence to Mark E. Venable.

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Webb, L.M., Arnholt, A.T. & Venable, M.E. Phospholipase D modulation by ceramide in senescence. Mol Cell Biochem 337, 153–158 (2010). https://doi.org/10.1007/s11010-009-0294-z

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  • DOI: https://doi.org/10.1007/s11010-009-0294-z

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