c-FLIP-L recombinant adeno-associated virus vector infection prevents Fas-mediated but not nerve growth factor withdrawal-mediated cell death in PC12 cells.
Fas is a cell surface death receptor that may play an important role in regulating cell death in neuronal cell types by activation of caspase 8. Cellular FLICE inhibitory protein-long (c-FLIP-L) is an endogenous inhibitor of the activation of caspase 8 by Fas. The current study addresses the role of c-FLIP-L in regulation of cell death in PC12 cells induced by nerve growth factor (NGF) withdrawal and Fas antibody, which acts as a Fas ligand and activates the Fas receptor. A recombinant adeno-associated virus (rAAV) vector that expresses c-FLIP-L was constructed. PC12 cells infected with the c-FLIP-L rAAV were resistant to apoptosis induced by treatment with Fas antibody compared to cells infected with enhanced green fluorescent protein (EGFP) expressing rAAV. Overexpression of c-FLIP-L rAAV inhibited cleavage of caspase 8 induced by Fas antibody treatment. In contrast, treatment with the c-FLIP-L rAAV did not protect PC12 cells from cell death induced by NGF withdrawal. In conclusion, overexpression of c-FLIP-L rAAV inhibits Fas antibody-mediated cell death, but not NGF withdrawal-mediated cell death in PC12 cells.
Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Shasha
S
Wu
Liqiao
L
Zhou
Marie
M
Rose
Xiao
X
Xiao
Steven H
SH
Graham
D000257:Adenoviridae Infections; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015153:Blotting, Western / Q000379:methods; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins / Q000235:genetics / Q000494:pharmacology*; D053181:Caspase 8; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D000229:Dependovirus / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry / Q000379:methods; D005822:Genetic Vectors / Q000378:metabolism; D020287:In Situ Nick-End Labeling / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins; D020932:Nerve Growth Factor / Q000172:deficiency*; D009479:Neuropeptides / Q000276:immunology / Q000502:physiology*; D016716:PC12 Cells; D051381:Rats; D018124:Receptors, Tumor Necrosis Factor; D013997:Time Factors; D019014:fas Receptor
D000906:Antibodies; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins; C491898:Fas protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor; D020932:Nerve Growth Factor; C505528:Casp8 protein, rat; D053181:Caspase 8; D020169:Caspases