title: Protein kinase C-mediated cell death mode switch induced by high glucose.
abstract: Cortical neurons rapidly die in necrosis due to poor glucose uptake in the low-density (LD) culture under serum-free condition without any supplements. The scanning and transmission electron microscopical analyses characterized the necrosis by membrane disruption, mitochondrial swelling and loss of cytoplasmic electron density. High-glucose treatment delayed the neuronal death by suppressing necrosis, but induced apoptosis through increase in Bax levels, cytochrome c release, caspase-3 activation and DNA ladder formation. Although pyruvate as well as high glucose inhibited necrotic cell death and rapid decrease in cellular ATP levels, possibly related to decreased [(3)H]-2-deoxy glucose uptake under the serum-free condition, it did not induce apoptosis. Protein kinase C inhibitors blocked these changes related to the cell death mode switch. Several neurotrophic factors did not affect the necrosis, but potentiated high-glucose-induced survival activity, while inhibiting cytochrome c release. All these results suggest that high-glucose treatment causes neuronal cell death mode switch by inhibiting necrosis, while inducing apoptosis, which is prevented by neurotrophic factors.
authors.affiliation: Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Fujita
authors.forename: H
authors.initials: H
authors.lastname: Ueda
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017304:Annexin A5 / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000196:embryology; D004396:Coloring Agents / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D053938:DNA Fragmentation; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D008858:Microscopy, Phase-Contrast; D008928:Mitochondria / Q000378:metabolism; D009336:Necrosis; D009474:Neurons / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D013997:Time Factors; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D017304:Annexin A5; D004396:Coloring Agents; D016895:Culture Media, Serum-Free; D000255:Adenosine Triphosphate; D045304:Cytochromes c; D007770:L-Lactate Dehydrogenase; D011493:Protein Kinase C; D010738:Type C Phospholipases; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D005947:Glucose