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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Elanchezhian, R. Palsamy, P. Madson, C. J. Mulhern, M. L. Lynch, D. W. Troia, A. M. Usukura, J. Shinohara, T. |
| Description | Country affiliation: United States Author Affiliation: Elanchezhian R ( Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA.) |
| Abstract | Aging is enhanced by hypoxia and oxidative stress. As the lens is located in the hypoglycemic environment under hypoxia, aging lens with diabetes might aggravate these stresses. This study was designed to examine whether low glucose under hypoxic conditions induces the unfolded protein response (UPR), and also if the UPR then generates the reactive oxygen species (ROS) in lens epithelial cells (LECs). The UPR was activated within 1 h by culturing the human LECs (HLECs) and rat LECs in <1.5 mM glucose under hypoxic conditions. These conditions also induced the Nrf2-dependent antioxidant-protective UPR, production of ROS, and apoptosis. The rat LECs located in the anterior center region were the least susceptible to the UPR, whereas the proliferating LECs in the germinative zone were the most susceptible. Because the cortical lens fiber cells are differentiated from the LECs after the onset of diabetes, we suggest that these newly formed cortical fibers have lower levels of Nrf2, and are then oxidized resulting in cortical cataracts. Thus, low glucose and oxygen conditions induce the UPR, generation of ROS, and expressed the Nrf2 and Nrf2-dependent antioxidant enzymes at normal levels. But these cells eventually lose reduced glutathione (GSH) and induce apoptosis. The results indicate a new link between hypoglycemia under hypoxia and impairment of HLEC functions. |
| File Format | HTM / HTML |
| e-ISSN | 20414889 |
| DOI | 10.1038/cddis.2012.40 |
| Journal | Cell Death and Disease |
| Volume Number | 3 |
| Language | English |
| Publisher | Nature Publishing Group |
| Publisher Date | 2012-04-19 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Immunohistochemistry Research Support, N.i.h., Extramural Reactive Oxygen Species Cytology Glucose Cell Hypoxia Antioxidants Ischemia Glutathione Lens Cortex, Crystalline Cells, Cultured Rats, Sprague-dawley Epithelial Cells Pharmacology Metabolism Unfolded Protein Response Drug Effects Discipline Cell Biology Pathology Animals Nf-e2-related Factor 2 Apoptosis |
| Content Type | Text |
| Resource Type | Article |
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