Hypoxia-induced apoptosis of dorsal root ganglion neurons is associated with DNA damage recognition and cell cycle disruption in rats.
The metabolic effects of hyperglycemia and hypoxia are important in the pathogenesis of diabetic neuropathy. We demonstrated apoptosis in dorsal root ganglion neurons in vitro by employing an oxygen-glucose deprivation model that uses dorsal root ganglia incubated in room air (pO2=150 torr) followed by hypoxic conditions (pO2=7.6 torr). Apoptosis was confirmed by demonstrating caspase-3 activation by immunocytochemistry. Immunocytochemistry and western blot analysis demonstrated an increase in activated p53, suggesting that DNA damage was occurring. Cell cycle disruption was examined by cyclin D1 expression. Neuronal death was associated with up-regulation of markers associated with DNA damage and aberrant entry into G1 of the cell cycle.
Honma
Hiroyuki
H
Department of Neurology, Cellular Neurobiology Laboratory, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
Gross
LouAnn
L
Windebank
Anthony J
AJ
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000378:metabolism; D004249:DNA Damage / Q000502:physiology*; D003929:Diabetic Neuropathies / Q000209:etiology / Q000378:metabolism*; D005333:Fetus; D016193:G1 Phase / Q000502:physiology; D005727:Ganglia, Spinal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D051379:Mice; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; C505409:Casp3 protein, mouse; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases