Laboratory for Leukocyte Signaling Research, 7-206 3rd St, Shinheung-dong, Jung-gu, Incheon 400-712, Korea.
J Clin Biochem Nutr. 2011 Jul;49(1):50-6. doi: 10.3164/jcbn.10-120. Epub 2011 Jun 17.
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 (H(2)O(2))-derived necrosis in macrophages. In this study, we examined further whether taurine chloramine could protect RAW 264.7 macrophages from apoptosis caused by H(2)O(2). Macrophages treated with 0.4 mM H(2)O(2) underwent apoptosis without showing immediate signs of necrosis, and the cells pretreated with taurine chloramine were protected from the H(2)O(2)-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 H(2)O(2). 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 H(2)O(2)-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.
牛磺酸氯胺是活化的中性粒细胞内通过过产生的次氯酸与储存的牛磺酸之间的反应产生的主要氯胺。牛磺酸氯胺通过抑制炎症介质的产生,在炎症组织中具有抗炎和细胞保护作用。牛磺酸氯胺增加血红素加氧酶的活性,并且还可以防止巨噬细胞中过氧化氢 (H₂O₂) 引起的坏死。在这项研究中,我们进一步研究了牛磺酸氯胺是否可以保护 RAW 264.7 巨噬细胞免受 H₂O₂引起的细胞凋亡。用 0.4 mM H₂O₂处理的巨噬细胞发生凋亡,而没有立即出现坏死的迹象,并且用牛磺酸氯胺预处理的细胞可以防止由 H₂O₂引起的细胞凋亡。牛磺酸氯胺增加血红素加氧酶-1 的表达和血红素加氧酶的活性。牛磺酸氯胺衍生的血红素加氧酶-1 表达的上调被 ERK 磷酸化的抑制所阻断。牛磺酸氯胺最初降低细胞内谷胱甘肽 (GSH) 水平,但 10 小时后 GSH 水平增加到对照水平之上。牛磺酸氯胺还增加了过氧化氢酶的表达,并保护巨噬细胞免受 H₂O₂的凋亡作用。综上所述,这些结果表明,由活化的中性粒细胞内产生和释放的内源性牛磺酸氯胺不仅可以通过增加血红素加氧酶-1 和过氧化氢酶等保护性酶的表达,还可以通过增加细胞内抗氧化剂 GSH 水平,来保护炎症组织中的巨噬细胞免受 H₂O₂诱导的凋亡。