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)

It is well established that the proto-oncogene, bcl-2, can prevent apoptosis induced by a variety of factors. Regarding the mechanism by which BCL-2 prevents cell death, one theory suggests that it acts by protecting cells from oxidative stress. In the lens system, oxidative stress-induced apoptosis is implicated in cataractogenesis. To explore the possibility of anti-apoptotic gene therapy development for cataract prevention and also to further test the anti-oxidative stress theory of BCL-2 action, we have introduced the human bcl-2 gene into an immortalized rabbit lens epithelial cell line, N/N1003A. The stable expression clones of both vector- and bcl-2-transfected cells have been established. Treatment of the two cell lines with H(2)O(2) revealed that bcl-2-transfected cells were less capable of detoxifying H(2)O(2) than the control cells. Moreover, bcl-2-transfected cells are more susceptible to H(2)O(2)-induced apoptosis. To explore why bcl-2-transfected cells have reduced resistance to H(2)O(2)-induced apoptosis, we examined the expression patterns of several relevant genes and found that expression of the alphaB-crystallin gene was distinctly down-regulated in bcl-2-transfected cells compared with that in vector-transfected cells. This down-regulation was specific because a substantial inhibition of BCL-2 expression through antisense bcl-2 RNA significantly restored the level of alphaB-crystallin and, moreover, enhanced the ability of the bcl-2-transfected cells against H(2)O(2)-induced apoptosis. Introduction of a mouse alphaB-crystallin gene into bcl-2-transfected cells also counteracted the BCL-2 effects. Down-regulation of alphaB-crystallin gene was largely derived from changed lens epithelial cell-derived growth factor activity. Besides, alphaB-crystallin prevents apoptosis through interaction with procaspase-3 and partially processed procaspase-3 to prevent caspase-3 activation. Together, our results reveal that BCL-2 can regulate gene expression in rabbit lens epithelial cells. Through down-regulation of the alphaB-crystallin gene, BCL-2 attenuates the ability of rabbit lens epithelial cells against H(2)O(2)-induced apoptosis.
 ...
PMID:Human bcl-2 gene attenuates the ability of rabbit lens epithelial cells against H2O2-induced apoptosis through down-regulation of the alpha B-crystallin gene. 1154 95

Epidemiologic studies have revealed a higher incidence of cataracts in estrogen-deprived postmenopausal women, although the pathogenic mechanism has not yet been elucidated. Apoptosis of lens epithelial cells has been associated with cataractogenesis. The aim of the study reported here was to investigate the effect of estrogen replacement therapy (ERT) on lens epithelial cell apoptosis in an experimental rat model. Forty female Wistar rats were randomized into four groups: ERT (17beta-estradiol, 10 microg/kg/day) for 3 months without ovariectomy (group 1) and with ovariectomy (group 2); only ovariectomy (group 3); sham operated (group 4). At the end of the third month, all rats were sacrificed in estrous cycle, as determined by the vaginal smear test, and their right eyes were enucleated. Enucleated eyes were analyzed by immunohistochemical methods for the expression of terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end (TUNEL), caspase-3, and bcl-2 labeling. The TUNEL, caspase-3, and bcl-2 staining scores were found to increase in group 3 rats following the ovariectomy compared to the sham-operated group. The ERT decreased these scores in rats with or without the ovariectomy; however, these differences were not statistically significant. These data suggest that estrogen does not significantly affect lens epithelial cell apoptosis. Further studies are needed to gain a better understanding of the protective mechanism of estrogen and to provide new ideas for the treatment and prevention of cataract.
 ...
PMID:Effect of estrogen replacement therapy on lens epithelial cell apoptosis in an experimental rat model. 1996 48

This study aimed to examine and analyze the expression levels of hsa-miR-15a and hsa-miR-16-1 in lens epithelial cells from patients with age-related cataract to understand better the roles of these microRNAs in the pathogenesis of this disease. Lens epithelial cells of 60 age-related cataract patients (including 20 with cortical cataracts, 20 with nuclear cataracts, and 20 with posterior subcapsular cataracts) and 20 normal patients were included in the study. Real-time PCR was used to detect the expression of hsa-miR-15a-5p, hsa-miR-15a-3p, hsa-miR-16-1-5p, and hsa-miR-16-1-3p. Expression of the target genes of these microRNAs, namely bcl-2 and mcl-1, was also evaluated. hsa-miR-15a-5p, hsa-miR-15a-3p, and hsa-miR-16-1-5p were expressed at low levels in normal lens epithelial cells but at significantly higher levels in corresponding cells of patients with cortical, nuclear, or posterior subcapsular cataracts (P < 0.01). hsa-miR-16-1-3p was expressed at relatively high levels in normal lens epithelial cells but significantly decreased expression, or none at all, was detected in cells of patients from each cataract group (P < 0.01). Concerning their target genes bcl-2 and mcl-1, expression was detectable in normal lens epithelial cells, but their levels were significantly decreased in cataract patients, irrespective of type (P < 0.01). Expression of hsa-miR-15a-5p, hsa-miR-15a-3p, and hsa-miR-16-1-5p rose in lens epithelial cells in the three types of age-related cataract, which may suppress the expression of the anti-apoptotic genes bcl-2 and mcl-1, thereby contributing to the pathogenesis of age-related cataract through apoptosis.
...
PMID:Expression of the microRNAs hsa-miR-15a and hsa-miR-16-1 in lens epithelial cells of patients with age-related cataract. 2593 80