Biological autoxidation. II. Cholesterol esters as inert barrier antioxidants. Self-assembly of porous membrane sacs. An hypothesis.
The antioxidation defenses recognized thus far appear too weak. Needed are inert barriers to encapsulate foci of activated oxygen (FAOs) and contain their spreading. These capsules must: 1. self-assemble nonenzymatically and spontaneously in face of adversity; 2. resist oxidation and dissolution in water; and 3. be moderately fluid and elastic enough to withstand flexing by tissues. Evidence shows activated oxygen: a. is produced by common cholesterolester (CE)-raising agents; b. boosts accumulation of CEs; and c. splits low-density lipoproteins (LDL), thus releasing CE-rich coalescence-prone lipid micelles. I am proposing that CEs, combined with polar lipids, are uniquely suited to form inert-lipid antioxidation barriers (ILABs). Porous ILAB capsules self-assemble from lipid micelles released by oxidatively degraded LDL. The capsules are thermodynamically unstable but elastic, durable and capable of self-repair through oxidation of ambient LDL. All capsules tend to contract into spheres. Enclosed needle-like "foreign bodies", such as asbestos, puncture the contracting capsules. Hence the odd bulbous architecture of asbestos bodies. ILABs protect from--and their failure initiates and promotes--carcinogenesis and atherosclerosis. ILABs may be mediators of membrane biogenesis. The loss of arterial flexibility in atherosclerosis protects ILAB capsules from breakage.
D000975:Antioxidants; D001161:Arteriosclerosis / Q000209:etiology; D055598:Chemical Phenomena; D002621:Chemistry; D002784:Cholesterol / Q000172:deficiency / Q000502:physiology; D002788:Cholesterol Esters / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D003094:Collagen / Q000502:physiology; D004548:Elasticity; D005547:Foreign Bodies / Q000150:complications; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000502:physiology*; D008247:Lysosomes / Q000502:physiology; D008566:Membranes / Q000502:physiology; D009369:Neoplasms / Q000209:etiology; D010084:Oxidation-Reduction
D000975:Antioxidants; D002788:Cholesterol Esters; D008055:Lipids; D003094:Collagen; D002784:Cholesterol