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Nerve growth factor inhibits apoptosis induced by tumor necrosis factor in PC12 cells
Author(s) -
Haviv Ronit,
Stein Reuven
Publication year - 1999
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19990201)55:3<269::aid-jnr1>3.0.co;2-3
Subject(s) - apoptosis , tumor necrosis factor alpha , nerve growth factor , caspase , programmed cell death , microbiology and biotechnology , biology , intrinsic apoptosis , proteases , cancer research , receptor , immunology , biochemistry , enzyme
Tumor necrosis factor‐α (TNFα) may play a role in at least some of the neuronal death that occurs following brain insults or in neurodegenerative diseases. It is therefore important to characterize the mechanism underlying apoptosis induced by TNFα in neuronal cells and to identify factors capable of protecting neurons from this death. In the present study, we characterized the apoptotic effect of TNFα in PC12 cells, a model system commonly used for studying neuronal apoptosis, and examined the role of Bcl‐2 and caspases in this process. We show that TNFα induces apoptosis in both naive and primed PC12 cells. The TNFα‐induced apoptosis was inhibited by nerve growth factor (NGF) but not by insulin. These findings suggest that the apoptotic effect of TNFα can be inhibited by trophic factors and that the survival‐promoting effect of NGF is mediated by a specific pathway not shared by all tyrosine kinase receptors. The effect of Bcl‐2 on TNFα‐induced apoptosis was examined in PC12 cells overexpressing Bcl‐2. These cells were resistant to TNFα‐induced apoptosis, suggesting that the apoptotic effect of TNFα in PC12 cells is mediated via a pathway controlled by Bcl‐2. Examination of the role of caspase‐3 like activity in TNFα‐induced apoptosis showed that caspase‐3‐like proteases are activated, and their substrate, poly (ADP‐ribose) polymerase, is cleaved following TNFα treatment. In addition, the broad‐spectrum inhibitor of caspases, benzyloxycarbonyl‐Val‐Ala‐Asp‐fluoromethylketone (Z‐VAD‐FMK), was found to inhibit the TNFα‐induced apoptosis of PC12 cells. These results suggest that caspases are activated following TNFα treatment and are needed for TNFα‐induced apoptosis in PC12 cells. J. Neurosci. Res. 55:269–277, 1999. © 1999 Wiley‐Liss, Inc.