tailieunhanh - Báo cáo khoa học: Role of ceramide kinase in peroxisome proliferatoractivated receptor beta-induced cell survival of mouse keratinocytes

Ceramide (Cer) is known to be a lipid mediator in apoptosis and to have an important role in cell fate, via control of intracellular Cer levels. Recently, ceramide kinase (CerK) was identified as an enzyme that converts Cer to ceramide 1-phosphate (C1P). We examined potential functions of CerK in the regulation of keratinocyte survival, and the possible involve-ment of peroxisome proliferator-activated receptor beta (PPARb). | ỊFEBS Journal Role of ceramide kinase in peroxisome proliferator-activated receptor beta-induced cell survival of mouse keratinocytes Kiyomi Tsuji1 Susumu Mitsutake2 Urara Yokose2 Masako Sugiura3 Takafumi Kohama4 and Yasuyuki Igarashi1 2 1 Laboratory of Biomembrane and BiofunctionalChemistry Faculty of Advanced Life Sciences Hokkaido University Sapporo Japan 2 Laboratory of Biomembrane and BiofunctionalChemistry Faculty of PharmaceuticalSciences Hokkaido University Sapporo Japan 3 BiologicalResearch Laboratories II Daiichi-Sankyo Co. Ltd. Tokyo Japan 4 Exploratory Research Laboratories I Daiichi-Sankyo Co. Ltd. Tokyo Japan Keywords cell survival ceramide ceramide 1-phosphate CerK PPARb Correspondence Y. Igarashi Laboratory of Biomembrane and BiofunctionalChemistry Faculty of Pharmaceutical Sciences and Faculty of Advanced Life Sciences Hokkaido University Nishi 6 Kita 12 Kita-ku Sapporo 060-0812 Japan Fax 81 11 706 4986 Tel 81 11 706 3970 E-mail yigarash@ Website http english Received 5 April2008 revised 26 May 2008 accepted 29 May 2008 doi Ceramide Cer is known to be a lipid mediator in apoptosis and to have an important role in cell fate via control of intracellular Cer levels. Recently ceramide kinase CerK was identified as an enzyme that converts Cer to ceramide 1-phosphate C1P . We examined potential functions of CerK in the regulation of keratinocyte survival and the possible involvement of peroxisome proliferator-activated receptor beta PPARb . PPARb is known to be a nuclear receptor acting as a ligand-inducible transcription factor and has been implicated in the control of keratinocyte survival. In the mouse keratinocyte cell line SP1 serum starvation induced cell death and the accumulation of intracellular Cer an apoptotic event. However apoptosis was inhibited by activation of PPARb. Interestingly activation of PPARb enhanced the mRNA expression of CerK and CerK .