Potentiation of early necrotic death of glucose-starved pheochromocytoma 12 cells by nerve growth factor.
Recently suggested is an arguable hypothesis that neurotrophins can induce necrosis but suppress apoptosis of target cells in some pathological conditions. We examined this hypothesis by tracing the type of NGF-promoted cell death occurring in a hypoglycemic condition at various angles, such as kinetic analyses, histological examinations of membrane alterations, morphological observations in ultra-structural changes, and determinations of DNA fragmentation. Glucose-starved cell death consisted of two kinetically different stages, suggesting that it be mixed with early and delayed death. Several lines of evidence revealed that NGF prominently enhanced the early death with necrotic characters. By contrast, apoptotic characters of glucose-starved delayed death were not much affected by NGF. Nifedipine, a voltage-gated calcium channel blocker, could completely compensate for the enhancement of the early glucose-starved death by NGF. Interestingly, the NGF-promoted cell death was also blocked by cycloheximide that did not keep PC12 cells alive from glucose starvation. Therefore, all the data in this study suggest that NGF accelerates the early necrosis of glucose-starved cell death probably through the alterations of intracellular calcium ions and protein syntheses.
Hong
J H
JH
Department of Biology and Center for Cell Signaling Research, Ewha Womans University, Seoul, Korea.
Hur
K C
KC
Chung
J M
JM
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002462:Cell Membrane / Q000648:ultrastructure; D002467:Cell Nucleus / Q000648:ultrastructure; D003513:Cycloheximide / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D007700:Kinetics; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D009336:Necrosis; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D009543:Nifedipine / Q000494:pharmacology; D016716:PC12 Cells; D014176:Protein Biosynthesis / Q000187:drug effects; D051381:Rats
D002121:Calcium Channel Blockers; D020932:Nerve Growth Factor; D003513:Cycloheximide; D009543:Nifedipine; D005947:Glucose