Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, United States.
Biochem Pharmacol. 2013 Mar 15;85(6):839-48. doi: 10.1016/j.bcp.2012.11.018. Epub 2012 Dec 19.
The glutathione S-transferases (GSTs) provide cellular protection by detoxifying xenobiotics, maintaining redox status, and modulating secondary messengers, all of which are critical to maintaining olfaction in salmonids. Here, we characterized the major coho salmon olfactory GSTs (OlfGSTs), namely omega, pi, and rho subclasses. OlfGST omega contained an open reading frame of 720bp and encoded a protein of 239 amino acids. OlfGST pi and OlfGST rho contained open reading frames of 627 and 681nt, respectively, and encoded proteins of 208 and 226 amino acids. Whole-protein mass spectrometry yielded molecular weights of 29,950, 23,354, and 26,655Da, respectively, for the GST omega, pi, and rho subunits. Homology modeling using four protein-structure prediction algorithms suggest that the active sites in all three OlfGST isoforms resembled counterparts in other species. The olfactory GSTs conjugated prototypical GST substrates, but only OlfGST rho catalyzed the demethylation of the pesticide methyl parathion. OlfGST pi and rho exhibited thiol oxidoreductase activity toward 2-hydroxyethyl disulfide (2-HEDS) and conjugated 4-hydroxynonenal (HNE), a toxic aldehyde with neurodegenerative properties. The kinetic parameters for OlfGST pi conjugation of HNE were K(M)=0.16 ± 0.06mM and V(max)=0.5 ± 0.1μmolmin⁻¹mg⁻¹, whereas OlfGST rho was more efficient at catalyzing HNE conjugation (K(M)=0.022 ± 0.008 mM and V(max)=0.47 ± 0.05μmolmin⁻¹mg⁻¹). Our findings indicate that the peripheral olfactory system of coho expresses GST isoforms that detoxify certain electrophiles and pesticides and that help maintain redox status and signal transduction.
谷胱甘肽 S-转移酶(GSTs)通过解毒异生物、维持氧化还原状态和调节二级信使来提供细胞保护,所有这些对维持鲑鱼的嗅觉都至关重要。在这里,我们描述了主要的银大麻哈鱼嗅觉 GST(OlfGSTs),即 omega、pi 和 rho 亚类。OlfGST omega 含有一个 720bp 的开放阅读框,编码一个 239 个氨基酸的蛋白质。OlfGST pi 和 OlfGST rho 分别含有 627 和 681nt 的开放阅读框,编码 208 和 226 个氨基酸的蛋白质。全蛋白质谱法分别得出 GST omega、pi 和 rho 亚基的分子量为 29950、23354 和 26655Da。使用四种蛋白质结构预测算法进行同源建模表明,所有三种 OlfGST 同工型的活性位点都类似于其他物种的对应位点。嗅觉 GST 共轭原型 GST 底物,但只有 OlfGST rho 催化杀虫剂甲基对硫磷的脱甲基化。OlfGST pi 和 rho 对 2-羟乙基二硫化物(2-HEDS)和共轭 4-羟基壬烯醛(HNE)表现出硫醇氧化还原酶活性,HNE 是一种具有神经退行性的有毒醛。OlfGST pi 共轭 HNE 的动力学参数为 K(M)=0.16±0.06mM 和 V(max)=0.5±0.1μmolmin⁻¹mg⁻¹,而 OlfGST rho 催化 HNE 共轭的效率更高(K(M)=0.022±0.008mM 和 V(max)=0.47±0.05μmolmin⁻¹mg⁻¹)。我们的研究结果表明,银大麻哈鱼的外周嗅觉系统表达 GST 同工型,可解毒某些亲电体和杀虫剂,并有助于维持氧化还原状态和信号转导。