Peroxide-induced effects on lens cation transport following inhibition of glutathione reductase activity in vitro

Giblin, Frank J.; McCready, Janet P.; Schrimscher, Lisa; Reddy, Venkat N.

doi:10.1016/s0014-4835(87)80080-5

Cited by 68 publications

(41 citation statements)

References 33 publications

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“…This is further confirmed by our finding that an H 2 O 2 concentration of 100 ÌM caused loss of transparency in the epithelium and superficial lens fibers in 1 h. Although the lenses cleared after some hours, damage was severe enough to cause cell death in the epithelium and vacuole formation in the periphery of the anterior side of the lens. These vacuoles have previously been described in cultured rabbit lenses by Giblin et al [34] after treatment with an inhibitor of glutathione reductase and 3 h of exposure to 50 ÌM H 2 O 2 . When viewed under a phase contrast microscope, the anterior side of the lenses exposed to 100 H 2 O 2 for 1 h exhibited a nodular/granular appearance underneath the epithelium.…”

Section: Discussionmentioning

confidence: 54%

“…According to Giblin et al [34] 50 ÌM H 2 O 2 seems to be the threshold for what the lens can tolerate since this level of hydrogen peroxide did not cause apparent damage to the lens but higher concentration resulted in vacuole formation and inhibition of the Na + -K + -ATPase. When rabbit lenses were exposed to a single dose of 50 ÌM H 2 O 2 for 3 h and subsequently kept in peroxide-free medium for 24 h, there was no cytotoxic damage to the lens epithelium [36].…”

Section: Discussionmentioning

confidence: 98%

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Calcium-Dependent Proteolysis in Rabbit Lens Epithelium after Oxidative Stress

Andersson

Sjöstrand²,

Petersen³

et al. 1998

Ophthalmic Res

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The purpose of this study was to examine changes in calcium-dependent proteolytic activity in the lens epithelium from whole rabbit lenses exposed to long-term oxidative stress at near physiological levels. Rabbit lenses, incubated in 50 µM H₂O₂ for 1 or 24 h, were checked for clarity and morphological changes in the epithelium. Proteolytic activity was measured in the epithelium using a fluorogenic synthetic substrate; N-succinyl-Leu-Tyr-7-amino-4-methylcoumarin, both in the presence and the absence of calcium (1 mM Ca²⁺ and 5 mM EDTA respectively). The effect on transparency and morphology of the epithelium following a 1-hour incubation in 100 µM H₂O₂ was also studied. Lenses incubated in 50 µM H₂O₂ were clear even after 24 h. After a 1-hour incubation in 50 µM H₂O₂ the epithelium of the exposed lens appeared normal. However, after 24 h the epithelium cells appeared swollen and microscopical examination showed extensive intracellular and subepithelial vacuolization. Incubation in 100 µM H₂O₂ for 1 h caused loss of transparency; vacuole formation, globulization of the superficial lens fibers and death of the epithelial cells. There was a 55% increase in calcium-dependent proteolytic activity after 1 h in 50 µM H₂O₂, implying a role for the calcium-activated protease calpain in oxidatively induced cataract.

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Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 98%

Calcium-Dependent Proteolysis in Rabbit Lens Epithelium after Oxidative Stress

Andersson

Sjöstrand²,

Petersen³

et al. 1998

Ophthalmic Res

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“…For experiments with HiOj, 0.05 mM H1O2 was added to the media and maintained at this level as described elsewhere [12,13]. At the end of the incu bation period, lenses were analyzed for 86Rb and GSH content.…”

Section: Methodsmentioning

confidence: 99%

Effect of Glutathione Depletion on Cation Transport and Metabolism in the Rabbit Lens

et al. 1988

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The role of reduced glutathione (GSH) in lens membrane function was studied by depleting GSH with 1-chloro-2,4-dinitrobenzene (CDNB), a reaction catalyzed by GSH-S-transferase. Depletion of GSH in the lens epithelium by 70–90% led to a decrease in uptake and increase in efflux of ⁸⁶Rb. ATP levels and Na⁺/K⁺-ATPase activity were normal while there was a slight decrease in lactate production. The results provide the first direct evidence that depletion of endogenous GSH per se does not lead to inactivation of Na⁺/K⁺-ATPase. However, lenses deficient in GSH when challenged with a normally tolerated level of H₂O₂ showed significant inactivation of membrane ATPase without a further increase in membrane permeability. Pretreatment with CDNB resulted in a 3-fold stimulation of the hexose monophosphate shunt activity which is attributed to the unexpected finding of a significant increase in the level of oxidized glutathione in the lens. It is concluded that deficiency of GSH causes a marked increase in membrane permeability and such lenses are susceptible to oxidative damage resulting in inactivation of the Na⁺/K⁺ pump, thus leading to ionic changes and cataract development.

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“…It is generally believed that for a significant proportion of this population, oxidative stress is an initiating or major contributing factor (4). This viewpoint is supported by a large body of evidence indicating that (i) oxidants such as H202 can cause cataracts (5,6), (ii) in some patients, aqueous humor and lens H202 levels are elevated to concentrations that will cause cataracts in model systems (7)(8)(9), and (iii) analyses of human cataracts indicate extensive oxidation of lens proteins (10-13) and lipids (14,15). Recent work suggests that DNA damage found in human lens epithelial cells isolated from cataract patients may have been caused by oxidative stress (16,17).…”

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confidence: 92%

Photochemically induced cataracts in rat lenses can be prevented by AL-3823A, a glutathione peroxidase mimic.

Spector

Wang

1993

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

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Oiddatve stress is known to cause cataracts In lens culture systems and is believed to be an important factor contributing to human cataracts. In this communication, it is demonstrated that cataract development of cultured rat lenses produced as a result of photochemkaily induced oxidation in a 4% oxygen atmosphere imilar to the native environment ofthe lens can be blocked by the ttion metal complex AL-3823A. In this system, riboflavin is added to the medium as a photosensitizer. AL-3823A acts primarily as a glutathione peroxidase mimic, which catalyticafly metabdoi H202 and also has low superoide dimutaeke activity. Mamsurements of H202,°2 -and OH te that appreciable levels of the first two of these oxidants and low levels of OHf are produced by this photochemical sreing system. The H202 concentrations are milar to those found in some patients with cataracts. The development of cataracts was followed over a 96-hr period.Transparency, hydration, glyceraldehyde-3-phosphate dehydrogenase activy, and protein and nonprotein thiol were monitored. AU parameters show marked chang during the 96-hr period. However, in the presence of 200 pM AL-3823A, no difference between control and light-exposed lenses was observed with respect to these parameters. The results suggest that in Wvo human cataract development caused by oxidative str may be prevented by compounls of this type.One ofthe major problems confronting investigators studying cataracts is that of definitively defining the factors that initiate the loss of opacity. For certain types of cataracts, the relationship between cause and effect is obvious. Thus, in diabetic cataracts, it is generally accepted that osmotic shock induced by the formation of sugar alcohols initiates the development ofopacification (1), and in congenital cataracts, it probably is a genetic defect that causes the pathology (2, 3). Numerous animal models for cataracts have been developed that utilize oxidative or osmotic stress and, in some cases, mutation as the initiating factor (3). However, with maturityonset cataract, a disease that afflicts a majority of people in later life, the causes are difficult to define. It is generally believed that for a significant proportion of this population, oxidative stress is an initiating or major contributing factor (4). This viewpoint is supported by a large body of evidence indicating that (i) oxidants such as H202 can cause cataracts (5, 6), (ii) in some patients, aqueous humor and lens H202 levels are elevated to concentrations that will cause cataracts in model systems (7-9), and (iii) analyses of human cataracts indicate extensive oxidation of lens proteins (10-13) and lipids (14,15

show abstract

Peroxide-induced effects on lens cation transport following inhibition of glutathione reductase activity in vitro

Cited by 68 publications

References 33 publications

Calcium-Dependent Proteolysis in Rabbit Lens Epithelium after Oxidative Stress

Calcium-Dependent Proteolysis in Rabbit Lens Epithelium after Oxidative Stress

Effect of Glutathione Depletion on Cation Transport and Metabolism in the Rabbit Lens

Photochemically induced cataracts in rat lenses can be prevented by AL-3823A, a glutathione peroxidase mimic.

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