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

Although it has been known for many years that opacification of the human lens is accompanied by oxidation of cysteine sulfhydryl groups to half-cystine residues, nothing is known concerning the exact amino acid sequences involved in this oxidative process. Since alpha-A crystallin is one of the major proteins of the lens, and since a decrease in its molecular chaperone activity has been implicated in possible mechanisms of cataract formation, alpha-A crystallin was purified from total lens proteins by reverse phase chromatography, followed by digestion with lys-C endoprotease. Mass spectral analysis of the digest indicated that in normal transparent lenses, cys-131 and cys-142 from alph-A crystallin are present as a mixture of cysteine sulfhydryl and half-cysteine disulfide groups, while identical analysis from cataractous lenses demonstrated undetectable levels of the cysteine sulfhydryl group. Together, these results demonstrate for the first time, the involvement of specific cysteine residues in the oxidative mechanism of human lens opacification.
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PMID:Oxidation of cysteine residues from alpha-A crystallin during cataractogenesis of the human lens. 867 Feb 61

1-cys peroxiredoxin (1-cysPrx), a member of the peroxiredoxin family with a single conserved cysteine residue, reduces a broad spectrum of hydroperoxides. This study was undertaken to examine changes in 1-cysPrx expression in human cataract samples, human lens epithelial (HLE B3) cell line, and rat organ-cultured lenses in response to oxidative insult induced by H2O2 or transforming growth factor-beta1 (TGF-beta1). Expression of 1-cysPrx mRNA and protein in HLE B3 cells increased in response to 2-8 ng ml(-1) TGF-beta1 and 50-75 microm H2O2 and then decreased below the control level at high doses (10 ng ml(-1) TGF-beta1 and 100-150 microm H2O2), as determined by Northern blot and immunoblot analysis. This reduction coincided with the decrease of cell viability. Immunoreactive 1-cysPrx protein was measured in capsulorrhexis specimens obtained from patients with anterior subcapsular cataract (ASC), nuclear sclerosis (NS), cortical spokes (CS), posterior subcapsular cataract (PSC), or white mature cataract (WC) at the time of cataract surgery. Significant reduction of 1-cysPrx protein was observed in ASC, PSC, and WC samples, but there was no statistical difference in CS and NS samples relative to normal control. Also, rat lens explants were cultured with 10 ng ml(-1) TGF-beta1 for approximately 5 days or 500 microm H2O2 for approximately 2 days. Subsequently, expression of 1-cysPrx mRNA and protein in the lens capsules was evaluated. Rat lens explants treated with TGF-beta1 or H2O2 developed a cataract similar to human ASC or WC, respectively, which resulted in a markedly decreased expression of 1-cysPrx mRNA and protein. Collectively, these findings show that expression patterns of 1-cysPrx gene in the lens are changed in response to oxidative stress, a major factor in the etiology of cataract.
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PMID:Reduced expression of 1-cys peroxiredoxin in oxidative stress-induced cataracts. 1636 Jun 53