Comparative study of survival signal withdrawal- and 4-hydroxynonenal-induced cell death in cerebellar granule cells.
The lipid peroxidation product, 4-hydroxynonenal (HNE), has been shown to induce apoptosis in PC12 cells and hippocampal neurons. We compared the degree of cell death induced by survival signal withdrawal (K+ and serum deprivation) with that induced by HNE, and investigated whether agents that block survival signal withdrawal-induced apoptosis could also prevent HNE-induced cell death in cultured cerebellar granule cells. Cell death induced by K+ and serum deprivation was inhibited by cycloheximide, a CPP 32-like protease inhibitor (Ac-DEVD-CHO) and a pituitary adenylate cyclase-activating polypeptide (PACAP)-38. In addition, nuclear cyclic AMP responsive element (CRE)- and activator protein 1 (AP-1) DNA-binding activities were increased 2 h after K+ and serum withdrawal, and these increases were inhibited by cycloheximide, Ac-DEVD-CHO and PACAP 38. Although these agents also blocked HNE-induced cell death, consistent with their efficacy in preventing survival signal withdrawal-induced cells death, CRE and AP-1 DNA-binding activities were decreased in a time-dependent manner during HNE-induced cell death. These results suggest that mechanistic differences exist between apoptosis induced by HNE and that induced by withdrawal of survival signals in cerebellar granule neurons.
Ito
Y
Y
Department of Pharmacology, College of Pharmacy, Nihon University, Funcabashi-shi, Chiba, Japan.
Arakawa
M
M
Ishige
K
K
Fukuda
H
H
D051698:Activating Transcription Factor 2; D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000502:physiology*; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism
D051698:Activating Transcription Factor 2; D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D000447:Aldehydes; D017362:Cyclic AMP Response Element-Binding Protein; D015853:Cysteine Proteinase Inhibitors; D008565:Membrane Proteins; D014157:Transcription Factors; C027576:4-hydroxy-2-nonenal