Kim Chaekyun, Cha Young-Nam
Laboratory for Leukocyte Signaling Research and Center for Advanced Medical Education by BK21 Project, Incheon, Korea.
Adv Exp Med Biol. 2009;643:463-72. doi: 10.1007/978-0-387-75681-3_48.
Taurine is abundantly present in phagocytic cells and provides protection against cytotoxicity caused by reactive oxygen species (ROS). The reaction between taurine and HOCl, a toxic product of the myeloperoxidase (MPO) system, generates a more stable and less toxic product, taurine chloramine (TauCl). TauCl has also been shown to inhibit the production of superoxide anion (O2-) and nitric oxide (NO). In this review, we compare the effect of taurine and TauCl on the production of these reactive species in phagocytes. First, TauCl inhibit PMA-derived O2- production and this is associated with inhibition of p47phox phosphorylation and of p47phox and p67phox translocation. Second, TauCl inhibits LPS-induced iNOS expression and NO production. This occurs by direct inhibition of Ras activation, ERK1/2 phosphorylation and NF-kappaB activation. Third, TauCl by itself increases the expression of heme oxygenase-1 (HO-1) and enhances HO activity. Carbon monoxide (CO), a product of HO activity, is able to inhibit both O2- and NO production. Combined, these effects of TauCl appear to provide cytoprotection against the inadvertent cytotoxicity caused by overproduction of O2- and NO.
牛磺酸大量存在于吞噬细胞中,并能保护细胞免受活性氧(ROS)引起的细胞毒性作用。牛磺酸与髓过氧化物酶(MPO)系统的毒性产物次氯酸(HOCl)之间的反应会生成一种更稳定且毒性更小的产物——牛磺氯胺(TauCl)。研究还表明,TauCl能够抑制超氧阴离子(O2-)和一氧化氮(NO)的生成。在本综述中,我们比较了牛磺酸和TauCl对吞噬细胞中这些活性物质生成的影响。首先,TauCl抑制佛波酯(PMA)诱导的O2-生成,这与抑制p47phox磷酸化以及p47phox和p67phox易位有关。其次,TauCl抑制脂多糖(LPS)诱导的诱导型一氧化氮合酶(iNOS)表达和NO生成。这是通过直接抑制Ras激活、细胞外信号调节激酶1/2(ERK1/2)磷酸化和核因子κB(NF-κB)激活来实现的。第三,TauCl自身可增加血红素加氧酶-1(HO-1)的表达并增强HO活性。HO活性的产物一氧化碳(CO)能够抑制O2-和NO的生成。综合来看,TauCl的这些作用似乎能为细胞提供保护,使其免受因O2-和NO过度生成而导致的意外细胞毒性。