Up-regulation of NDRG2 in senescent lens epithelial cells contributes to age-related cataract in human.
| Autor: | Zi-Feng Zhang, Jian Zhang, Yan-Nian Hui, Min-Hua Zheng, Xin-Ping Liu, Peter F Kador, Yu-Sheng Wang, Li-Bo Yao, Jian Zhou |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: | |
| Zdroj: | PLoS ONE, Vol 6, Iss 10, p e26102 (2011) |
| Druh dokumentu: | article |
| ISSN: | 1932-6203 40492702 |
| DOI: | 10.1371/journal.pone.0026102 |
| Popis: | BACKGROUND: Human N-Myc downstream regulated gene2 (NDRG2), a novel gene has been cloned and shown to be related to a number of cellular processes, including proliferation, differentiation, stress, and apoptosis. NDRG2 has also been linked to age-related Alzheimer's disease. Since the role of this gene in senescence is limited, we have investigated the potential role of NDRG2 in human lens epithelial cells (HLECs), a paradigm implicated in age-related cataract. METHODOLOGY/PRINCIPAL FINDINGS: Cultured HLECs (SRA01/04) were subjected to prolonged exposure to low dose of H(2)O(2) to simulate senescence. After being exposed to 50 µM H(2)O(2) for 2 weeks, HLECs senescent-morphological changes appeared, cell viability decreased dramatically, cell proliferation reduced from 37.4% to 16.1%, and senescence-associated β-galactosidase activity increased from 0 to 90.3%. Ndrg2 protein expression was also significantly increased in these senescent cells. To induce overexpression of NDRG2, SRA01/04 cells were infected with the adenoviral vector of NDRG2. In these cells, overexpression of NDRG2 resulted in a fibroblast-like appearance and the cell viability decreased about 20%. In addition, the NDRG2-overexpression cells demonstrated 20% lower viability when exposed to 50-200 µM H(2)O(2) for acute oxidative stress. Furthermore, the expression of NDRG2 from age-related cataracts was up-regulated 2-fold at both mRNA and protein levels compared with the clear lenses. CONCLUSIONS/SIGNIFICANCE: NDRG2 is up regulated not only in the ageing process of HLECs in vitro but also in the cells from human age-related cortical cataract in vivo. Up-regulation of NDRG2 induces cell morphological changes, reduces cell viability, and especially lowers cellular resistance to oxidative stress. NDRG2-mediated affects in HLECs may associate with age-related cataract formation. |
| Databáze: | Directory of Open Access Journals |
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