Up-regulation of NDRG2 in senescent lens epithelial cells contributes to age-related cataract in human

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

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

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 2O 2 to simulate senescence. After being exposed to 50 μM H 2O 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 2O 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.

Original languageEnglish (US)
Article numbere26102
JournalPloS one
Volume6
Issue number10
DOIs
StatePublished - Oct 17 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Zhang, Z. F., Zhang, J., Hui, Y. N., Zheng, M. H., Liu, X. P., Kador, P. F., Wang, Y. S., Yao, L. B., & Zhou, J. (2011). Up-regulation of NDRG2 in senescent lens epithelial cells contributes to age-related cataract in human. PloS one, 6(10), [e26102]. https://doi.org/10.1371/journal.pone.0026102