Rabbit Anti-Human GSTM2 (a.a. 121-218) Polyclonal antibody

Aminochrome, an orthoquinone formed during the dopamine oxidation of neuromelanin, is neurotoxic because it induces mitochondria dysfunction, protein degradation dysfunction (both autophagy and proteasomal systems), alpha-synuclein aggregation to neurotoxic oligomers, neuroinflammation, and oxidative and endoplasmic reticulum stress. In this study, we investigated the relationship between aminochrome-induced autophagy/lysosome dysfunction and mitochondrial dysfunction in U373MGsiGST6 cells. Aminochrome (75 mu M) induces mitochondrial dysfunction as determined by (i) a significant decrease in ATP levels (70%; P < 0.001) and (ii) a significant decrease in mitochondrial membrane potential (P < 0.001). Interestingly, the pretreatment of U373MGsiGST6 cells with 100 nM bafilomycin-A1, an inhibitor of lysosomal vacuolar-type H+-ATPase, restores ATP levels, mitochondrial membrane potential, and mitophagy, and decreases cell death. These results reveal (i) the importance of macroautophagy/the lysosomal degradation system for the normal functioning of mitochondria and for cell survival, and (ii) aminochrome-induced lysosomal dysfunction depends on the aminochrome-dependent inactivation of the vacuolar-type H+-ATPase, which pumps protons into the lysosomes. This study also supports the proposed protective role of glutathione transferase mu2-2 (GSTM2) in astrocytes against aminochrome toxicity, mediated by mitochondria] and lysosomal dysfunction.

Aims: Morphine strongly induces reactive oxygen species (ROS). The deleterious actions of morphine can be countered by antioxidant system. In the present study, we investigated the expression levels of nine antioxidant genes in human SH-SY5Y cells treated with morphine. Main methods: The cells were treated with three final concentrations of morphine (1, 5, and 10 mu mol) for four exposure times (1 h, 24 h, 72 h and 18 days). The mRNA levels were determined using quantitative real-time RCR. Key findings: Based on the alterations of mRNA levels, the genes might be categorized into three different groups: In the first group, the mRNA levels of the CAT, SOD1 and GSTM3 genes were significantly down-regulated in all examined experimental conditions. In the second group, the mRNA levels of SOD2, NQO1, GSTM2 and GSTO1 were initially increased and then decreased. In the third group, the mRNA levels of NQO2 and GSTP1, were initially increased and then reached to the control levels. The number of down-regulated genes were significantly increased as a function of exposure time (chi(2) = 7.52, P = 0.006). We investigated the effect of morphine (10 mu mol) in the absence and presence of N-acetyl-cysteine (NAC, 1 mmol). The mRNA levels revealed significant differences between cells exposed to morphine and cells co-treated with morphine plus NAC. In cases that morphine increased the level of mRNAs, morphine plus NAC, result in decreased mRNA levels and vice versa. Significance: These findings suggested that there are different pathways for regulation of antioxidant genes after SH-SY5Y cells exposed to morphine and morphine might act through inducing ROS. (C) 2015 Published by Elsevier Inc.