Characterization of phospholipid hydroperoxide glutathione metabolizing peroxidase (gpx4) isoforms in Coho salmon olfactory and liver tissues and their modulation by cadmium

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• 作者：Lu Wang ; Sean M. Harris ; Herbert M. Espinoza ; Valerie McClain ; Evan P. Gallagher ; ^{evang3@uw.edu} ; ^{evang3@u.washington.edu}
• 关键词：GPx4 ; Cadmium ; Olfactory injury ; Coho salmon
• 刊名：Aquatic Toxicology
• 出版年：2012
• 期刊代码：19_0166445x
• 类别：abs
• 出版时间：15 June, 2012
• 卷：114-115
• 期：Complete
• 页码：134-141
• 文件大小：930 K

摘要

Exposure to environmental contaminants, including various pesticides and trace metals, can disrupt critical olfactory-driven behaviors of fish such as homing to natal streams, mate selection, and an ability to detect predators and prey. These neurobehavioral injuries have been linked to reduced survival and population declines. Despite the importance of maintaining proper olfactory signaling processes in the presence of chemical exposures, little is known regarding chemical detoxification in the salmon olfactory system, and in particular, the antioxidant defenses that maintain olfactory function. An understudied, yet critical component of cellular antioxidant defense is phospholipid hydroperoxide glutathione peroxidase (PHGPx/GPx4), an isoform within the family of selenium-dependent glutathione peroxidase (GPx) enzymes that can directly reduce lipid peroxides and other membrane-bound complex hydroperoxides. In this study, we cloned two m>gpx4m> isoforms (m>gpx4am> and m>gpx4bm>) from Coho salmon olfactory tissues and compared their modulation in olfactory and liver tissues by cadmium, an environmental pollutant and olfactory toxicant that cause oxidative damage as a mechanism of toxicity. Amino acid sequence comparisons of the two m>gpx4m> isoforms shared 71%identity, and also relatively high sequence identities when compared with other fish GPx4 isoforms. Sequence comparisons with human GPx4 indicated conservation of three important active sites at selenocysteine (U46), glutamine (Q81), and tryptophan (W136), suggesting similar catalytic activity between fish and mammalian GPx4 isoforms. Tissue profiling confirmed the expression of m>gpx4am> and m>gpx4bm> in all ten Coho tissues examined. The expression of m>gpx4m> mRNAs in the Coho olfactory system was accompanied by comparably high initial rates of GPx4 enzymatic activity in mitochondrial and cytosolic fractions. Exposure to low (3.7 ppb) and high (347 ppb) environmental Cd concentrations for 24-48 h significantly decreased m>gpx4am> expression in Coho olfactory rosettes, whereas olfactory m>gpx4bm> mRNA expression was not modulated by exposures at these concentrations. In summary, Coho salmon express two paralogs of m>gpx4m>, a key enzyme in the maintenance of signal transduction processes that protect against cellular oxidative damage. The Cd-associated downregulation of salmon olfactory m>gpx4am> expression in particular, may be associated with the loss of olfactory signal transduction that accompanies metal-associated loss of olfaction in salmonids.