Effect of oxidative stress on receptors and signal transmission.
Reactive oxygen metabolites affect binding of ligands to membrane receptors and also coupling of receptors to G-proteins and effector enzymes. Peroxidation of membrane lipids may lead to a lowered receptor density and also will alter the viscosity of the plasma membrane, which affects receptor coupling. Reactive oxygen species may also interact with thiol/disulfide moieties on receptor proteins or on other factors in the receptor system, which is responsible for alterations in receptor binding or coupling. Moreover, lipid peroxidation is associated with the phospholipase A2 pathway, which might indirectly affect receptor function. Moreover, oxidative stress may lead to a disturbance in cellular Ca(2+)-homeostasis. This might be related to an effect on Ca(2+)-mobilizing receptors, but there is also evidence for a decreased Ca(2+)-sequestration by ATPases. In addition, peroxidation of membrane lipids increases membrane permeability to Ca2+. Finally, reactive oxygen species interfere with actions of nitric oxide, thus affecting another pharmacological messenger system.
Van der Vliet
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Department of Pharmacochemistry, Faculty of Chemistry, Vrije Universiteit, Amsterdam, The Netherlands.
Bast
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D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000633:toxicity*; D011941:Receptors, Adrenergic / Q000187:drug effects* / Q000502:physiology; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D013312:Stress, Physiological / Q000139:chemically induced* / Q000503:physiopathology
D017382:Reactive Oxygen Species; D011941:Receptors, Adrenergic; D011976:Receptors, Muscarinic