Effects of x-irradiation on lens reducing systems. [Rabbits]

Giblin, Frank J.; Chakrapani, B; Reddy, V.N.

doi:10.2172/6294947

Cited by 11 publications

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“…in the lens (40)(41)(42)(43). The core portion of the lens is devoid of cell organelles; the cells of the peripheral zone, which are rich in mitochondria, are of major metabolic and protective importance.…”

Section: Resultsmentioning

confidence: 99%

“…The lens contains a relatively high level of GSH, and it is notable that many types of cataracts are associated with decreased levels of GSH in the lens (4)(5)(6)(7)(8)(9)(10). Administration of buthionine sulfoximine (BSO) (11), an effective inhibitor of -t-glutamylcysteine synthetase (the enzyme that catalyzes the first step in the biosynthesis of GSH), to mice and rats leads to markedly decreased levels of GSH in many tissues (12)(13)(14).…”

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confidence: 99%

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Glutathione ester prevents buthionine sulfoximine-induced cataracts and lens epithelial cell damage.

Mårtensson

Steinherz

Jain

et al. 1989

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

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BiochemistryGlutathione ester prevents buthionine sulfoximine-induced cataracts and lens epithelial cell damage [mitochondria/glutathione mono(glycyl) Contributed by Alton Meister, August 30, 1989 ABSTRACT Treatment of newborn rats and mice with buthionine sulfoximine, an inhibitor of glutathione synthesis, leads to development of cataracts, which are not prevented by treatment with glutathione, but they are prevented by treatment with glutathione monoester. Cataracts are associated with glutathione deficiency in the lens epithelium, which undergoes severe degeneration. The findings indicate that glutathione normally functions in the protection of the lens and lens epithelium against oxidative injury, suggesting that procedures that increase lens glutathione levels might be useful for prevention of other types of cataracts. Relatively low doses of buthionine sulfoximine produce cataracts in newborn animals, and treatment of pregnant mice with buthionine sulfoximine during the last part of gestation leads to cataract formation in the offspring. The high sensitivity of the developing lens to the effects of glutathione deficiency suggests that this tissue may be a useful model for studies on glutathione function.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Glutathione ester prevents buthionine sulfoximine-induced cataracts and lens epithelial cell damage.

Mårtensson

Steinherz

Jain

et al. 1989

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

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“…Thus, the aging guinea pig lens appears to be identical to the aging human lens with regard to an absence of substantial increase in -SS-level, as long as the lens remains transparent. It has been believed for many years that lens crystallins will not disulfide-crosslink until the level of GSH in a particular region of the lens has reached a critically low level (Kinoshita and Merola, 1959;Giblin et al, 1979;Giblin, 2000). It is thought that when the level of GSH drops below 1mM in the lens nucleus, PSSP formation and eventual nuclear cataract is initiated.…”

Section: Discussionmentioning

confidence: 99%

Raman spectroscopic evidence for nuclear disulfide in isolated lenses of hyperbaric oxygen-treated guinea pigs

Gosselin

Kapustij

Venkateswaran

et al. 2007

Experimental Eye Research

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Our laboratory treats guinea pigs with hyperbaric oxygen (HBO) as a model for investigating the formation of nuclear cataract. Previous analyses of lens supernatants using this model have shown an increase in disulfide (-SS-) and loss of sulfhydryl (-SH) in the lens nucleus of O 2 -treated animals. In this paper, we have used the non-invasive technique of Raman spectroscopy to confirm these findings in intact, freshly-excised lenses. Guinea pigs were treated 3 times per week with HBO for a total of 50 (4 months of treatment) or 85 (7 months of treatment) times to induce an increased level of lens nuclear light scattering. Intact lenses were analyzed by Raman spectroscopy using a 514.5 nm laser and collecting the scattered light in a 90° geometry. The laser beam was focused either in the lens nucleus or equatorial cortex. Changes in the levels of -SS-(503 cm −1 ) and -SH (2577 cm −1 ) vibrations were measured. Raman spectra were analyzed by fitting Lorentzian profiles to the observed data in the -SS-and -SH regions. -SS-levels in the O 2 -treated nucleus were found to have increased by a factor of 2.1 (p=0.0001) and 2.5 (p=0.001) after 50 and 85 HBO treatments, respectively, compared to age-matched controls. Based on previous biochemical analyses, the -SSincrease was due mainly to the formation of protein disulfide (PSSP) with contribution also from protein/thiol mixed disulfides, but not from oxidized glutathione. -SH levels in the O 2 -treated nucleus decreased by 13% (p=0.007) and 35% (p=0.001) after 50 and 85 HBO treatments, respectively, compared to age-matched controls. No significant increase in -SS-or loss of -SH was observed in the lens cortex of the O 2 -treated guinea pigs. The Raman spectroscopy results rule out the possibility that artifactual production of -SS-and loss of -SH occurred during homogenization of lenses in previous studies. The data provide additional evidence to support a link between O 2 , disulfidecrosslinking of lens crystallins in the nucleus, and nuclear cataract.

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“…However, the eventual expected Na+/K' imbalance may cause swelling and subsequent lysis, leading to increased membrane permeability. It is interesting to note that with rabbit lenses in organ culture, although t-butyl hydroperoxide concentrations < 1 mM do not cause short-term changes in membrane permeability, levels > 1 mM increase permeability (21).…”

Section: Discussionmentioning

confidence: 99%

H2O2-induced uncoupling of bovine lens Na+,K+-ATPase.

Garner¹,

Garner²,

Spector³

1983

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

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A 1-hr exposure of bovine lenses in organ culture to H202 concentrations in the range found in the aqueous fluid of patients with cataracts inhibits 86Rb+ influx. At 1 mM H202, complete inhibition was observed and further investigated. Membrane permeability is slightly decreased. Although lactate concentrations increase 2-fold, lens ATP concentrations decrease -10%, suggesting that glycolysis may be stimulated but ATP production is not able to keep up with the demand for energy. Examination of epithelial cell Mg-+-stimulated Na+,K+-ATPase isolated from the cultured lenses indicates H202-induced modification. At 5 mM MgATP, ATP hydrolysis is accelerated 30%; at 3 mM MgATP, hydrolysis is normal; and at 0.75 mM MgATP, it is inhibited 75%. p-Nitrophenyl phosphate hydrolysis and eosin maleimide binding indicate that K+ control of the enzyme is modified. Thus, a very early effect of H202 upon the lens, well before the formation of opacity, appears to be the uncoupling of Na+ and K+ transport from ATP hydrolysis.In cataracts Na', K+, and Ca2" concentrations appear to be altered (1). The change in cation concentrations may reflect either increased membrane permeability or altered function of the major lenticular cation pumps, Mg2+-stimulated Na+/ K+ ATPase and Ca2 ATPase. Recent studies indicate that with cataract development Na+,K+-ATPase appears to be increasingly inhibited (2).With cataract development there also is increased oxidation of certain lens protein amino-acid side chains (3). This fundamental oxidation process, which appears to start at the cell membrane, leads to conformational changes and crosslinking of the lens proteins with plasma membrane polypeptides acting as nucleation points. Eventually the fiber cell membrane ruptures and large aggregates containing membrane fragments, extrinsic membrane protein, and cytosol protein are formed (4).Because the oxidation of the membrane protein appeared to precede the oxidation of the cytoplasmic protein (3), these studies suggested that possibly deleterious oxidizing agents may arise outside the lens. Examination of the aqueous fluid surrounding the lenses indicated that in patients with cataracts, there are dramatically elevated concentrations of H202, ranging from 45 to 663 uM (5). A patient with Marfan syndrome had a H202 concentration >3 mM. These observations suggest that elevated exogenous H202 may be an important oxidizing agent involved in the formation of certain cataracts. This viewpoint is supported by the finding that in organ culture, H202 concentrations comparable to concentrations found in the aqueous fluid of patients with cataracts will cause the development of opacity within 48 hr (6).The lens has a number of defenses against oxidation caused by H202 and other agents (7). These defenses include catalase, glutathione peroxidase, superoxide dismutase, glutathione reductase, methionine sulfoxide reductase (8), a high concentration of glutathione, and a very active hexose monophosphate shunt. However, many of these defenses reside primarily...

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Effects of x-irradiation on lens reducing systems. [Rabbits]

Cited by 11 publications

References 11 publications

Glutathione ester prevents buthionine sulfoximine-induced cataracts and lens epithelial cell damage.

Glutathione ester prevents buthionine sulfoximine-induced cataracts and lens epithelial cell damage.

Raman spectroscopic evidence for nuclear disulfide in isolated lenses of hyperbaric oxygen-treated guinea pigs

H2O2-induced uncoupling of bovine lens Na+,K+-ATPase.

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