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[Studies on membrane factors in iron-supported lipid peroxidation]
1Hokkaido College of Pharmacy, Japan.
Abstract:
Lipid peroxidation in biomembranes is mediated by free radical reactions. It leads to membrane damage and has been proposed to be associated with the pathogenesis to tissue injuries. Iron is known as a catalyst of lipid peroxidation. Microsomal lipid peroxidation by both NADPH and iron-chelate, such as Fe(3+)-ADP or Fe(3+)-PPi, is believed to be enzymatically associated with iron reduction. On the other hand, the addition of free Fe2+ to microsomes or liposomes produces a lag phase before the maximal rates of lipid peroxidation. We examined the interaction of iron with membrane in iron-supported lipid peroxidation and microsomal membrane components associated with iron reduction in NADPH-supported lipid peroxidation. Iron-supported lipid peroxidation was affected by the surface charges of liposomal membrane. Liposomes containing phosphatidylserine (PS) were most sensitive to iron-supported lipid peroxidation. The effect of PS on iron-supported lipid peroxidation indicates that iron participates in binding to membrane surface charges and also indicates that Fe2+ at high level bound to membranes plays a role in producing a lag phase. The mechanism producing a lag phase in Fe(2+)-PPi-supported lipid peroxidation is discussed. In NADPH-supported lipid peroxidation in microsomes, it seemed unlikely that superoxide may be involved in iron reduction. Alternatively, under anaerobic conditions, NADPH-supported iron reduction in microsomes was not dependent on cytochrome P450 content and not inhibited by CO. A cholate-solubilized fraction of microsomes was applied to a laurate-Sepharose column and an active fraction for lipid peroxidation was obtained. Involvement of a heat-labile component, distinct from cytochrome P450, responsible for iron reduction in microsomal lipid peroxidation was demonstrated.
Insights
Iron catalyzes lipid peroxidation, damaging biomembranes. This study reveals iron interacts with membrane surface charges, influencing peroxidation rates and lag phases, and identifies a heat-labile component in microsomes responsible for iron reduction.
Area of Science:
- Biochemistry
- Cell Biology
Context:
- Lipid peroxidation is a free radical process damaging biomembranes and implicated in tissue injury.
- Iron is a known catalyst for lipid peroxidation, but its precise interactions with membranes and the mechanisms of iron reduction remain areas of investigation.
- NADPH-dependent lipid peroxidation in microsomes involves enzymatic iron reduction, distinct from superoxide involvement.
Purpose:
- To investigate the interaction of iron with membrane surface charges in iron-supported lipid peroxidation.
- To elucidate the role of membrane-bound iron in the lag phase observed during lipid peroxidation.
- To identify microsomal components responsible for iron reduction in NADPH-supported lipid peroxidation.
Summary:
- Iron-supported lipid peroxidation is influenced by liposomal membrane surface charges, with phosphatidylserine (PS)-containing liposomes showing heightened sensitivity.
- High levels of Fe2+ bound to membranes contribute to the lag phase in lipid peroxidation, suggesting iron's direct role in membrane interactions.
- NADPH-dependent iron reduction in microsomes occurs independently of cytochrome P450 and CO inhibition, pointing to a distinct, heat-labile component responsible for this process.
Impact:
- Findings clarify the role of iron in membrane damage and lipid peroxidation, offering insights into pathogenesis of tissue injuries.
- Identification of a novel heat-labile component involved in iron reduction provides a new target for understanding and potentially modulating lipid peroxidation.
- This research contributes to a deeper understanding of the biochemical mechanisms underlying iron-mediated oxidative stress in biological systems.