Cytochrome P450-mediated oxidative damage of nuclear membrane proteins and its prevention by vitamin C

In this report, we present data to indicate that NADPH-cytochrome P450 reductase/cytochrome P450 system is present in the nuclear membrane. The reactive oxygen species generated in this free metal ion-independent P450 system oxidatively modifies and degrades the membrane proteins. The oxidative modification is evidenced by the formation of carbonyl, bityrosine and tryptophan loss. The degradation of membrane proteins is manifested using fluorescamine reactivity and SDS-PAGE. Ascorbic acid exclusively prevents the oxidative modification and degradation of the membrane proteins. Other antioxidants, such as superoxide dismutase, catalase, glutathione, alpha-tocopherol, probucol, beta-carotene, mannitol, histidine and thiourea are found to be ineffective. The observation assumes significance, particularly in subclinical ascorbic acid deficiency, where oxidative damage of the nuclear membrane would occur. This, in turn, would affect the traffic of cytoplasmic enzymes and proteins required for DNA replication and repair, transcription and RNA processing, ultimately leading to disruption of gene regulation of the cell.