Upregulation of death pathway molecules in rat cerebellar granule neurons undergoing apoptosis.
Cerebellar granule neurons can be maintained in culture in a medium containing high serum and depolarising levels of KCl. When serum is removed and the KCl levels lowered from 25 to 5 mM, the cells undergo apoptosis. Apoptosis can be prevented by inhibitors of transcription or translation, suggesting a need for macromolecular synthesis in the apoptotic process. Using quantitative reverse transcription-polymerase chain reaction the levels of mRNA for a range of genes postulated to be important in apoptosis have been examined. Elevated levels of caspase 3, c-Jun, and Fas ligand were found, in addition to a corresponding increase in c-Jun protein and activation of caspase-3. These results suggest that cerebellar granule neurons upregulate components of both death receptor-mediated and the mitochondrial-mediated death pathways.
Ginham
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R
Anatomical Neuropharmacology Unit, Medical Research Council, OX1 3TH, Oxford, UK.
Harrison
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DC
Facci
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Skaper
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Philpott
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KL
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D053222:Fas Ligand Protein; D005786:Gene Expression Regulation / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology*
D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases