Abbreviations used : Aβ, amyloid β-peptide ; DCF, 2,7-dichlorofluorescein ; DEVD-CHO, N-acetyl-Asp-Glu-Val-Asp-aldehyde ; DHR, dihydrorhodamine-123 ; Par-4, prostate apoptosis response-4 ; PBS, phosphate-buffered saline ; ROS, reactive oxygen species ; TBARS, thiobarbituric acid-reactive species ; TFW, trophic factor withdrawal.
Prostate Apoptosis Response-4 Mediates Trophic Factor Withdrawal-Induced Apoptosis of Hippocampal Neurons
Actions Prior to Mitochondrial Dysfunction and Caspase Activation
Version of Record online: 18 JAN 2002
Journal of Neurochemistry
Volume 73, Issue 2, pages 502–512, August 1999
How to Cite
Chan, S. L., Tammariello, S. P., Estus, S. and Mattson, M. P. (1999), Prostate Apoptosis Response-4 Mediates Trophic Factor Withdrawal-Induced Apoptosis of Hippocampal Neurons. Journal of Neurochemistry, 73: 502–512. doi: 10.1046/j.1471-4159.1999.0730502.x
- Issue online: 18 JAN 2002
- Version of Record online: 18 JAN 2002
- Antisense oligodeoxynucleotide;
- Free radical;
- Mitochondrial membrane depolarization;
- Uric acid;
- Vitamin E.
Abstract : Prostate apoptosis response-4 (Par-4) is the product of a gene up-regulated in prostate cancer cells undergoing apoptosis. We now report that Par-4 mRNA and protein levels rapidly and progressively increase 4-24 h following trophic factor withdrawal (TFW) in cultured embryonic rat hippocampal neurons. The increased Par-4 levels follow an increase of reactive oxygen species, and precede mitochondrial membrane depolarization, caspase activation, and nuclear chromatin condensation/fragmentation. Pretreatment of cultures with 17β-estradiol, vitamin E, and uric acid largely prevented Par-4 induction and cell death following TFW, demonstrating necessary roles for oxidative stress and membrane lipid peroxidation in TFW-induced neuronal apoptosis. Par-4 antisense oligonucleotide treatment blocked Par-4 protein increases and attenuated mitochondrial dysfunction, caspase activation, and cell death following TFW. Collectively, our data identify Par-4 as an early and pivotal player in neuronal apoptosis resulting from TFW and suggest that estrogen and antioxidants may prevent apoptosis, in part, by suppressing Par-4 production.