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Influence of environmental and chemical factors on cellular signaling in lens epithelial cells
Abstract/OtherAbstract :
Cataract is the leading cause of vision loss worldwide and is treated only by surgical intervention. Oxidative stress-induced damage to the lens can accumulate with aging or exposure to environmental and/or chemical stressors. Lens epithelial cells (LEC) comprise the first cell layer exposed to stress, and LEC death is considered an initiating event in cataract development. Activation of stress-induced cell signaling pathways coordinates the LEC response to injury. The first objective of this research was to determine the mechanism(s) of cell death in human lens epithelial cells (HLE) exposed to environmental (ultraviolet B (UVB) radiation) and chemical stressors (hydrogen peroxide, (H 2O 2) and tertiary butyl hydroperoxide, (TBHP)). While all three stressors decreased HLE cell density, exposure to UVB resulted in changes in cell morphology, DNA fragmentation and annexin/propidium iodide staining consistent with apoptosis, whereas H 2O 2and TBHP treatment resulted in necrosis. Activation of signaling proteins such as JNK, c-Jun and DNA fragmentation factor 45 (DFF45) were observed only in UVB-treated cells. Gap junction intercellular communication (GJIC) facilitates nutrient transport in the lens, and is regulated by cell stress, cell signaling pathways and dietary compounds. The mechanism of this regulation is not clearly established, although changes in connexins, structural proteins of gap junction channels, is involved. Connexin 43 (Cx43) is the major connexin present in LEC. The second objective of this research was to examine the role of cell signaling pathways and the dietary compounds, retinoids and carotenoids, in modulating GJIC in canine LEC. Treatment with the protein kinase C (PKC) activator, TPA, significantly decreased GJIC in canine LEC and increased Cx43 phosphorylation. Inhibition of PKC partially restored TPA-inhibited GJIC and reduced Cx43 phosphorylation. Retinoic acid increased expression of Cx43 and enhanced GJIC in canine LEC. LEC utilize stress-induced signaling pathways to respond to environmental and chemical stressors. GJIC can be regulated by cell signaling pathways and dietary compounds in primary canine LEC. The long term application of this project includes a better understanding of the molecular mechanisms by which various stressors and dietary compounds modulate lens physiology and cataractogeneis in humans and animals.
Authors :
Long, Amy Carise
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Publisher :  Ohio State University / OhioLINK     Type :  text     Format :  -    
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Subject :
lens epithelial cell, cell signaling, environmental stress, chemical stress, primary canine lens, apoptosis, gap junction communication, connexin, retinoids, carotenoids, antioxidant, cataract
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Languages :  English    
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