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Low glucose under hypoxic conditions induces unfolded protein response and produces reactive oxygen species in lens epithelial cells

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...

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Autores principales: Elanchezhian, R, Palsamy, P, Madson, C J, Mulhern, M L, Lynch, D W, Troia, A M, Usukura, J, Shinohara, T
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3358018/
https://www.ncbi.nlm.nih.gov/pubmed/22513875
http://dx.doi.org/10.1038/cddis.2012.40
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author Elanchezhian, R
Palsamy, P
Madson, C J
Mulhern, M L
Lynch, D W
Troia, A M
Usukura, J
Shinohara, T
author_facet Elanchezhian, R
Palsamy, P
Madson, C J
Mulhern, M L
Lynch, D W
Troia, A M
Usukura, J
Shinohara, T
author_sort Elanchezhian, R
collection PubMed
description 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.
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spelling pubmed-33580182012-05-29 Low glucose under hypoxic conditions induces unfolded protein response and produces reactive oxygen species in lens epithelial cells Elanchezhian, R Palsamy, P Madson, C J Mulhern, M L Lynch, D W Troia, A M Usukura, J Shinohara, T Cell Death Dis Original Article 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. Nature Publishing Group 2012-04 2012-04-19 /pmc/articles/PMC3358018/ /pubmed/22513875 http://dx.doi.org/10.1038/cddis.2012.40 Text en Copyright © 2012 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Original Article
Elanchezhian, R
Palsamy, P
Madson, C J
Mulhern, M L
Lynch, D W
Troia, A M
Usukura, J
Shinohara, T
Low glucose under hypoxic conditions induces unfolded protein response and produces reactive oxygen species in lens epithelial cells
title Low glucose under hypoxic conditions induces unfolded protein response and produces reactive oxygen species in lens epithelial cells
title_full Low glucose under hypoxic conditions induces unfolded protein response and produces reactive oxygen species in lens epithelial cells
title_fullStr Low glucose under hypoxic conditions induces unfolded protein response and produces reactive oxygen species in lens epithelial cells
title_full_unstemmed Low glucose under hypoxic conditions induces unfolded protein response and produces reactive oxygen species in lens epithelial cells
title_short Low glucose under hypoxic conditions induces unfolded protein response and produces reactive oxygen species in lens epithelial cells
title_sort low glucose under hypoxic conditions induces unfolded protein response and produces reactive oxygen species in lens epithelial cells
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3358018/
https://www.ncbi.nlm.nih.gov/pubmed/22513875
http://dx.doi.org/10.1038/cddis.2012.40
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