Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutathione reductase (GR) plays a key role in maintaining thiol groups in the lens, and its activity decreases with aging and cataract formation. Mammalian thioredoxin (Trx) and thioredoxin reductase (TrxR), or the Trx/TrxR system, participates in the repair of oxidatively damaged lens proteins and enzymes. Alpha-crystallin, a molecular chaperone, prevents the aggregation of partially denatured proteins under various stress conditions. Thioltransferase (TTase, or glutaredoxin) can maintain the homeostasis of lens protein thiols thus protecting against oxidative stress. We investigated whether the Trx/TrxR system can revive GR activity in both the cortex and nucleus of human cataract and clear aged lenses and whether alpha-crystallin and TTase can help this effect. The GR activity in the cortex and nucleus of the cataractous lenses was significantly lower than that of the aged clear lenses. The highest activity in the cortex was observed in the clear aged lenses. The combination of Trx and TrxR revived the activity of GR from both the cortex and nucleus of aged clear lenses. However, in cataract lenses (grade II and grade IV), there was a statistically significant recovery of GR activity in the cortex, but not in the nucleus. No recovery was observed when Trx or TrxR were used separately. Alpha-crystallin successfully revived GR activity in the cortex of cataract grade II lenses, but not in the nucleus. The combination of alpha-crystallin and Trx/TrxR gave a further increase of activity. TTase alone revived some of the GR activity but together with the Trx/TrxR system gave no statistically significant enhancement of GR activity. These results indicate that both disulfide bond formation and protein unfolding are responsible for GR inactivation.
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PMID:Revival of glutathione reductase in human cataractous and clear lens extracts by thioredoxin and thioredoxin reductase, in conjunction with alpha-crystallin or thioltransferase. 1751 31

Selenite cataracts are effective and convenient animal models for simulation of human senile nuclear cataracts. These models are widely used to study the effects of various stresses on eye lenses and to screen anticataract drugs. However, there have been no comprehensive toxicological evaluations of these animal models. To investigate the effects of sodium selenite on some important organs in selenite cataract model animals, this study analyzed (1) histopathology by hematoxylin and eosin (H&E) staining; (2) methionine sulfoxide reductase (Msr) A and B1 protein expression; (3) glutathione peroxidase (GPx), thioredoxin reductase (TrxR) and superoxide dismutase (SOD) activity; and (4) malondialdehyde (MDA) levels in the liver, kidney, and brain in a selenite cataract rat model. The results showed that sodium selenite induced severe oxidative damage, especially in the hippocampus and corpus striatum of the brain, in Sprague-Dawley (SD) rats. This damage was evidenced by mild gliocyte proliferation, significant disorder of neuronal arrangement with acidophilic changes in the hippocampus, and significant occurrence of focal microglia or lymphocytic infiltration in the corpus striatum after selenite injection for cataract simulation. The damage was closely related to significant decreases in antioxidant enzyme expression and activity and significant increases in lipid peroxidation (MDA) levels. Furthermore, nonsignificant swelling and scattered spotty necrosis were observed in the liver. These results imply that physiological changes in model animals should be considered when carrying out anticataract drug screening and that pathological changes in other nontarget organs should be prevented.
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PMID:Effects of Sodium Selenite on Oxidative Damage in the Liver, Kidney and Brain in a Selenite Cataract Rat Model. 3183 24