Cholesterol Hydroperoxide Formation in Red Cell Membranes and Photohemolysis in Erythropoietic Protoporphyria

Lamola, Angelo A.; Yamane, T; Trozzolo, A. M.

doi:10.1126/science.179.4078.1131

Cited by 150 publications

(50 citation statements)

References 18 publications

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“…In some reports, singlet oxygen (102) has been proposed as the product (26,27), but in another report the formation of 0°-was also suggested (28). The requirement of oxygen for the photosensitivity of our mutant also suggests that some kinds of active oxygen are produced in the light.…”

Section: Discussionmentioning

confidence: 53%

Photosensitivity of a protoporphyrin-accumulating, light-sensitive mutant (visA) of Escherichia coli K-12.

Nakahigashi

Nishimura

Miyamoto

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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Mutations in the visA gene of Escherichia coli cause the mutant bacteria to die upon illumination with visible light. We confirmed genetically that the visA gene is a structural gene for ferrochelatase (protoheme ferro-lyase, EC 4.99.1.1). Since other mutations in the genes involved in the biosynthesis of heme can cure the photosensitivity, the light-induced cell death appears to be brought about by the accumulation of protoporphyrin IX, one of the substrates of ferrochelatase. When cells are illuminated with visible light, protoporphyrin IX seems to produce an active species of oxygen (probably 1O2) that is harmful to the cells. This defect is the same as that associated with the human disease protoporphyria.

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Section: Discussionmentioning

confidence: 53%

Photosensitivity of a protoporphyrin-accumulating, light-sensitive mutant (visA) of Escherichia coli K-12.

Nakahigashi

Nishimura

Miyamoto

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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“…Singlet oxygen is an effective initiator of lipid peroxidation (29). It is formed in vitro or physiologically by the energy of light being absorbed by dyes and then transmitted to dioxygen (29)-e. g., when light reaches blood pigments (30). It can also be formed by the decomposition ofendoperoxides (29).…”

Section: Methodsmentioning

confidence: 99%

Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis.

Ames¹,

Cathcart²,

Schwiers³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

2,526

1,609

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During primate evolution, a major factor in lengthening life-span and decreasing age-specific cancer rates may have been improved protective mechanisms against oxygen radicals. We propose that one ofthese protective systems is plasma uric acid, the level of which increased markedly during primate evolution as a consequence of a series of mutations. Uric acid is a powerful antioxidant and is a scavenger of singlet oxygen and radicals. We show that, at physiological concentrations, urate reduces the oxo-heme oxidant formed by peroxide reaction with hemoglobin, protects erythrocyte ghosts against lipid peroxidation, and protects erythrocytes from peroxidative damage leading to lysis. Urate is about as effective an antioxidant as ascorbate in these experiments. Urate is much more easily oxidized than deoxynucleosides by singlet oxygen and is destroyed by hydroxyl radicals at a comparable rate. The plasma urate level in humans (about 300 ILM) is considerably higher than the ascorbate level, making it one of the major antioxidants in humans. Previous work on urate reported in the literature supports our experiments and interpretations, although the findings were not discussed in a physiological context.Toxicity by oxygen radicals has been suggested as a major cause of cancer, heart disease, and aging (1-13). Oxygen radicals and other oxidants appear to be toxic in large part because they initiate the chain reaction of lipid peroxidation (rancidity). Lipid peroxidation generates various reactive species-such as radicals, hydroperoxides, aldehydes, and epoxides-with the capability of causing damage to DNA, RNA, proteins, cellular membranes, and cellular organization. Aerobic organisms have an array of protective mechanisms both for preventing the formation of oxidants and lipid peroxidation and for repairing oxidative damage. The protective systems include enzymes, such as superoxide dismutase (12) and the selenium-containing glutathione peroxidase (9, 10), and antioxidants and radical scavengers, such as a-tocopherol (vitamin E) and a-carotene in the lipid portion ofthe cell and glutathione and ascorbic acid in the aqueous phase (9, 10). These protective mechanisms are now being recognized as anticarcinogenic and, in some cases, even as life-span extending (5-7).A marked increase in life-span has occurred in human evolution during the descent from prosimians over the past 60 million years (4). At the same time an enormous decrease in the age-specific cancer rate has occurred in humans compared to short-lived mammals (14, 15). It seems likely that a major factor in lengthening life-span and decreasing age-specific cancer rates may have been the evolution ofeffective protective mechanisms against oxygen radicals (2-7, 10). We propose that one such mechanism is high plasma uric acid. MATERIALS AND METHODS'y-Ray Irradiation. Solutions of substrate (0.3 mM) in potassium phosphate buffer (20 mM, pH 7.4) were purged with 2, N2, or N20, sealed, and irradiated at room temperature with a 60Co y-ray source [12.7 krads/mi...

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“…As early as the 40's, Blum and Gilbert (1940) broadly defined the two possible sites of modification as proteins and lipids. More recently Lamola et al (1973) pointed out the need to consider cholesterol as a target apart from phospholipids and proteins. In a methodical series of reports VanSteveninck and co-workers systematically presented evidence that photohemolysis was the result not of carbohydrate , phospholipid (Schothorst et al, 1972) or cholesterol (DeGoeij and VanSteveninck, 1976) modification, but rather was due to modification of membrane proteins (Schothorst et al, 1972).…”

Section: Biochemistry Of Singlet Oxygen Modijication Of Membranesmentioning

confidence: 99%

Photomodification of Biological Membranes With Emphasis on Singlet Oxygen Mechanisms

Valenzeno

1987

Photochem & Photobiology

263

118

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Abstract-This review discusses photomodification of biological membranes and model membrane systems. Current concepts of membrane structure are first reviewed briefly. The role of preillumination association of sensitizer with membranes as it relates to photomodification rate is discussed, as well as the role of singlet oxygen in membrane photomodification. Finally the characteristics of singlet oxygen generation in membranes are considered. The evidence clearly indicates that membrane photomodification cannot be understood based only on the properties of sensitizers and singlet oxygen in aqueous solution. Rather the properties of sensitizers in association with membranes are the determinants of membrane photomodification. These properties differ significantly in aqueous solution and in membranes.

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Cholesterol Hydroperoxide Formation in Red Cell Membranes and Photohemolysis in Erythropoietic Protoporphyria

Cited by 150 publications

References 18 publications

Photosensitivity of a protoporphyrin-accumulating, light-sensitive mutant (visA) of Escherichia coli K-12.

Photosensitivity of a protoporphyrin-accumulating, light-sensitive mutant (visA) of Escherichia coli K-12.

Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis.

Photomodification of Biological Membranes With Emphasis on Singlet Oxygen Mechanisms

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