The role of superoxide and singlet oxygen in lipid peroxidation promoted by xanthine oxidase

Pederson, Thomas C.; Aust, Steven D.

doi:10.1016/0006-291x(73)91047-4

Cited by 203 publications

(40 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although many other aspects of the photolysis are still unknown (e.g., involvement of singlet oxygen, the mechanism of pigment destruction and the possible involvement of hydroxyl radicals), the identification of superoxide as a primary photoproduct has serious implications. Superoxide has been suggested to cause cleavage of DNA (34,35), depolymerization of acid polysaccharides (36,37), and peroxidation of unsaturated lipids (38)(39)(40). The conclusion from our experiments, that superoxide is produced in a primary photochemical event during the irradiation of pheomelanin, raises the question of the possible role of superoxide in ultraviolet-induced skin cancer and points out the importance of understanding its reactions with biological molecules.…”

mentioning

confidence: 64%

Photodestruction of pheomelanin: role of oxygen.

Chedekel¹,

Smith²,

Post³

et al. 1978

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

170

127

View full text Add to dashboard Cite

Pheomelanin, the red-brown polymeric pigment in the skin and hair of red-headed humans, is composed of a protein fraction covalently bound to a colored chromophore. Photolysis of aerated aqueous pheomelanin solutions, isolated from human red hair, results in destruction of the chromophore and liberation of the peptide fraction. The rate of photolysis depends on the pH and the concentration of both pigment and oxygen and is slightly inhibited by the enzyme superoxide dismutase (superoxide:superoxide oxidoreductase EC 1.15.1.1). Pheomelanin photolyzed in the presence of nitroblue tetrazolium results in the formation of a blue diformazan, whether or not oxygen is present. Superoxide dismutase inhibits the aerobic photoreduction of nitroblue tetrazolium whereas, in the absence of oxygen, no inhibition is observed. These experiments strongly suggest the involvement of superoxide in the aerobic photolysis of pheomelanin and point out a possible mechanism for ultraviolet-induced cell damage in redheads. The black or brown eumelanins of human skin afford protection against the damaging effects of the ultraviolet component in sunlight (1)(2)(3)(4). Light of these wavelengths, 280-380 nm, is nondestructive to eumelanin and produces reversible changes that are believed to function as mechanisms in this pigment's photoprotective ability. Two such reversible reactions are (i) immediate pigment darkening (3,5,6), an apparent oxidation-reduction reaction resulting in the darkening of preformed pigment, and (ii) an increase in the number and a change in the nature of the unpaired electrons in the pigment (7-9).Fair-skinned humans exhibit a number of abnormal reactions to sunlight, including freckling (10) and a high susceptibility to skin cancer (11)(12)(13)(14). These have usually been attributed to the fact that the skin of these people has a poor tanning capacity, sunburns readily, and contains little pigment. Although pheomelanin, the red-brown or yellow pigment found in the hair of fair-skinned humans (15,16), has yet to be isolated from human skin, there is an increasing amount of indirect evidence that it occurs in melanosomes found in various parts of the body, including the skin (17-22). Pheomelanin is readily photodegraded under physiologically relevant conditions (23, 24), an observation that has led us to suggest the following four mechanisms by which ultraviolet light may deleteriously affect cells containing this pigment: (i) loss of a pigment purportedly responsible for photoprotection; (ii) formation of dermatitic or carcinogenic photoproducts; (Mii) formation of dermatitic or carcinogenic compounds by reactions of photochemically produced intermediates with normal cell constituents; and (iv) formation of photoproducts that inhibit the enzymatic systems responsible for repair of ultraviolet-induced damage. In this paper we support the viability of mechanism iii by presenting evidence that a highly reactive intermediate is formed during the course of the photolysis.The publication costs of this article we...

show abstract

mentioning

confidence: 64%

Photodestruction of pheomelanin: role of oxygen.

Chedekel¹,

Smith²,

Post³

et al. 1978

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

170

127

View full text Add to dashboard Cite

show abstract

“…Oxygen tension and ascorbic acid also influence cyclic GMP levelsin tissues (45). The formation or utilization of superoxide ion is involved in thromboxane and prostaglandin formation (46), peroxidation of membranes (30,47), reduction of oxygen by flavin enzymes (48), autooxidation of hemoglobin (49), phagocytosis and lysosomal enzyme release from leukocytes (50), and other processes. Some of these processes can influence cyclic GMP levels in tissues.…”

Section: Resultsmentioning

confidence: 99%

Activation of guanylate cyclase by superoxide dismutase and hydroxyl radical: a physiological regulator of guanosine 3',5'-monophosphate formation.

Mittal¹,

Murad²

1977

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

208

View full text Add to dashboard Cite

Partially purified soluble rat liver guanylate cyclase [GTP pyrophosphate-lyase (cyclizing) METHODS AND MATERIALSMale Sprague-Dawley rats weighing 150-250 g were sacrificed by cervical dislocation. Livers were removed quickly and placed in cold 0.25 M sucrose containing 10 mM Tris-HCI buffer, pH 8.0/1 mM EDTA/1 mM dithiothreitol. Livers were homogenized in 8 volumes of this medium with a glass homogenizer and Teflon pestle at 4°. Homogenates were centrifuged at 105,000 X g for 60 min, and supernatant fractions were used for purification of guanylate cyclase as described (13,15,16). HC1 (1 M) was added to the supernatant fraction to yield pH 5.0. The precipitate was collected by centrifugation at 12,000 X g for 15 min, suspended in 50 mM Tris-HCl, pH 7.6/1 mM EDTA/1 mM dithiothreitol, and recentrifuged. Solid ammonium sulfate was added to the resulting supernatant fraction to obtain 20% saturation. The precipitate was removed by centrifugation at 12,000 X g for 15 min and discarded.Ammonium sulfate was added to the supernatant fraction to achieve 45% saturation. The resulting precipitate was dissolved in 10 mM Tris-HCl, pH 7.6/1 mM EDTA/1 mM dithiothreitol. The sample was desalted on a Sephadex G-25 column and chromatographed on DEAE-cellulose (15,16). Guanylate cyclase was eluted by using a NaCI gradient (0-0.5 M). Fractions containing guanylate cyclase were pooled and used as a source of partially purified enzyme. Fresh preparations or those stored at -70°for more than 2 years were qualitatively similar in these studies.Guanylate cyclase activity was determined in 100-g1 incu-4360

show abstract

“…For example, Pederson and Aust [ 18,191 showed that EDTA stimulated lipid peroxidation, whereas other workers reported an inhibition [24-271. EDTA should promote 0; --dependent lipid peroxidation by chelating any Mn2+ and/or Cu2+ present, so preventing them from scavenging 0; -.…”

Section: Discussionmentioning

confidence: 99%