Taurine chloramine protects RAW 264.7 macrophages against hydrogen peroxide-induced apoptosis by increasing antioxidants

摘要

Taurine chloramine is the major chloramine generated in activated neutrophils via the reaction between the overproduced hypochlorous acid and the stored taurine. Taurine chloramine has anti-inflammatory and cytoprotective effects in inflamed tissues by inhibiting the production of inflammatory mediators. Taurine chloramine increases heme oxygenase activity and also protects against hydrogen peroxide (H2O2)-derived necrosis in macrophages. In this study, we examined further whether taurine chloramine could protect RAW 264.7 macrophages from apoptosis caused by H2O2. Macrophages treated with 0.4 mM H2O2 underwent apoptosis without showing immediate signs of necrosis, and the cells pretreated with taurine chloramine were protected from the H2O2-derived apoptosis. Taurine chloramine increased heme oxygenase-1 expression and heme oxygenase activity. The taurine chloramine-derived upregulation of heme oxygenase-1 expression was blocked by inhibition of ERK phosphorylation. Taurine chloramine decreased cellular glutathione (GSH) levels initially, but the GSH level increased above the control level by 10 h. Taurine chloramine also increased catalase expression and protected macrophages from the apoptotic effect of H2O2. Combined, these results indicate that the taurine chloramine, produced and released endogenously by the activated neutrophils, can protect the macrophages in inflamed tissues from the H2O2-derived apoptosis not only by increasing the expression of cytoprotective enzymes like heme oxygenase-1 and catalase, but also by increasing the intracellular antioxidant GSH level.