Protein kinase C-mediated necrosis-apoptosis switch of cortical neurons by conditioned medium factors secreted under the serum-free stress.
Cortical neurons die in necrosis in the low-density (LD) culture, and in apoptosis in the high-density (HD) culture under the serum-free condition without any supplements. The neuronal death in LD culture was delayed by conditioned medium (CM) factors prepared from the HD culture. The CM switched the cell death mode from necrosis to apoptosis, characterized by various cell death markers and transmission electron microscopy. The CM inhibited the rapid decrease in cellular ATP levels and [3H]-2-deoxy glucose ([3H]-2-DG) uptake in the LD culture. Inhibitors of phospholipase C and protein kinase C effectively abolished the CM-induced elevation of survival activity, [3H]-2-DG uptake and ATP levels, and necrosis-apoptosis switch. All these results suggest that CM caused the cell death mode switch from necrosis to apoptosis through phospholipase C- and protein kinase C-mediated mechanisms.
Fujita
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R
Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Ueda
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H
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002545:Brain Ischemia / Q000201:enzymology / Q000503:physiopathology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000201:enzymology / Q000503:physiopathology / Q000648:ultrastructure; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D003847:Deoxyglucose / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008854:Microscopy, Electron; D009336:Necrosis; D009414:Nerve Growth Factors / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D013312:Stress, Physiological / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism
D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D009414:Nerve Growth Factors; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D007770:L-Lactate Dehydrogenase; D011493:Protein Kinase C; D010738:Type C Phospholipases