The effects of oxidative stress on mitochondrial transmembrane potential in retinal ganglion cells.
Retinal ganglion cells (RGCs) are central neurons that undergo apoptosis after axonal injury. As the relationship between mitochondrial and oxidative signaling of apoptosis in neuronal systems is unclear, we sought to achieve a better understanding of the interplay of these two pathways by investigating the effect of direct oxidative stress on mitochondrial membrane potential in cultured RGCs, as measured with the dual-emission probe JC-1. Treatment with hydrogen peroxide caused RGC mitochondrial depolarization. Several pharmacological treatments were used to define the mechanism. Whereas cycloheximide, tris(2-carboxyethyl)phosphine, and cyclosporin A were unable to prevent the depolarization, bongkrekic acid significantly reduced the severity of the depolarization. This suggests that the hydrogen peroxide-induced depolarization may act through mitochondrial permeability transition pore opening independent of thiol oxidation, and may be preventable under certain conditions.
Lieven
Christopher J
CJ
Vrabec
Joshua P
JP
Levin
Leonard A
LA
D000818:Animals; D000831:Animals, Newborn; D001865:Bongkrekic Acid / Q000494:pharmacology; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology*; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D018384:Oxidative Stress / Q000502:physiology*; D010720:Phosphines / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000502:physiology*; D013438:Sulfhydryl Compounds / Q000378:metabolism
D001865:Bongkrekic Acid; D003513:Cycloheximide; D016572:Cyclosporine; D006861:Hydrogen Peroxide; D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D010720:Phosphines; D011500:Protein Synthesis Inhibitors; D013438:Sulfhydryl Compounds; C080938:tris(2-carboxyethyl)phosphine