Sigma 1 receptor stimulation protects against oxidative damage through suppression of the ER stress responses in the human lens

Wang, Lixin, Eldred, Julie A, Sidaway, Peter, Sanderson, Julie, Smith, Andrew J. O., Bowater, Richard P ORCID: https://orcid.org/0000-0002-2745-7807, Reddan, John R and Wormstone, I Michael ORCID: https://orcid.org/0000-0002-6423-7766 (2012) Sigma 1 receptor stimulation protects against oxidative damage through suppression of the ER stress responses in the human lens. Mechanisms of Ageing and Development, 133 (11-12). pp. 665-674. ISSN 0047-6374

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Abstract

Stimulation of sigma-1 receptors is reported to protect against oxidative stress. The present study uses cells and tissue from the human lens to elucidate the relationship between the sigma 1 receptor, ER stress and oxidative stress-induced damage. Exposure of the human lens cell line FHL124 to increasing concentrations of HO led to reduced cell viability and increased apoptosis. In response to 30µM HO, levels of the ER stress proteins BiP, ATF6 and pEIF2a were significantly increased within 4h of exposure. Expression of the sigma 1 receptor was markedly increased in response to HO. Application of 10 and 30µM (+)-pentazocine, a sigma 1 receptor agonist, significantly inhibited the HO induced cell death. (+)-Pentazocine also suppressed the oxidative stress induced reduction of pro-caspase 12 and suppressed the induction of the ER stress proteins BiP and EIF2a. When applied to cultured human lenses, (+)-pentazocine protected against apoptotic cell death, LDH release and against HO induced opacification. These data demonstrate that stimulation of the sigma 1 receptor provides significant protection from oxidative damage and is, therefore, a putative therapeutic approach to delay the onset of diseases that may be triggered by oxidative damage, including cataract formation.

Item Type: Article
Additional Information: Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Uncontrolled Keywords: sigma 1 receptor,oxidative stress,er stress,human,lens,cataract,sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School: Faculty of Science > School of Biological Sciences
Faculty of Science > School of Pharmacy
UEA Research Groups: Faculty of Science > Research Groups > Pharmaceutical Cell Biology (former - to 2017)
Faculty of Science > Research Groups > Molecular Microbiology
Faculty of Science > Research Groups > Cells and Tissues
Faculty of Science > Research Groups > Molecular and Tissue Pharmacology
Faculty of Science > Research Centres > Centre for Molecular and Structural Biochemistry
Faculty of Science > Research Groups > Biosciences Teaching and Education Research
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Depositing User: Pure Connector
Date Deposited: 26 Jun 2013 09:40
Last Modified: 04 Jan 2024 02:48
URI: https://ueaeprints.uea.ac.uk/id/eprint/42520
DOI: 10.1016/j.mad.2012.09.005

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