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http://dx.doi.org/10.4062/biomolther.2010.18.3.262

Roles of Neutral Sphingomyelinase 1 on CD95-Mediated Apoptosis in Human Jurkat T Lymphocytes  

Lee, Hyun-Min (College of Pharmacy, Chung-Ang University)
Surh, Bo-Young (College of Pharmacy, Chung-Ang University)
Chun, Young-Jin (College of Pharmacy, Chung-Ang University)
Publication Information
Biomolecules & Therapeutics / v.18, no.3, 2010 , pp. 262-270 More about this Journal
Abstract
CD95 receptor is a member of tumor necrosis factor receptor family that mediates apoptosis in many cell types when bound by CD95 ligand or cross-linked by agonistic anti-CD95 antibodies. To determine the role of neutral sphingomyelinase (nSMase) on CD95-mediatd apoptosis, human Jurkat T lymphocytes were exposed to recombinant human CD95 ligand. Treatment with CD95 ligand induced cell death in a concentration and time-dependent manner. CD95-induced cell death was suppressed by inhibitors of SMase such as AY9944 or desipramine. Transfection with human nSMase1 siRNA plasmid into CD95 ligand-treated cells significantly prevented CD95-mediated cell death. CD95-mediated elevation of intracellular ceramide level detected by FACS analysis with anti-ceramide antibody was also decreased by nSMase1 siRNA. Knock-down of nSMase1 expression also blocked cytochrome c release into cytosol and caspase-3 cleavage in CD95-treated cells. Taken together, these results suggest that nSMase1 may play an important role in CD95-mediated apoptotic cell death in Jurkat T cells.
Keywords
CD95 ligand; nSMase1; Jurkat T cell; siRNA; Apoptosis;
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