Kiang Juliann G, Krishnan Sandeep, Lu Xinyue, Li Yansong
Armed Forces Radiobiology Research Institute, Bldg. 46, Room 2423, 8901 Wisconsin Ave., Bethesda, MD 20889-5603, USA.
Mol Pharmacol. 2008 Mar;73(3):738-47. doi: 10.1124/mol.107.041079. Epub 2007 Dec 13.
Sodium cyanide-induced chemical hypoxia triggers a series of biochemical alterations leading to apoptosis in many cell types, including T cells. It is known that chemical hypoxia promotes inducible nitric-oxide synthase (iNOS) gene transcription by activating its transcription factors. To determine whether iNOS and NO production are responsible for chemical hypoxia-induced apoptosis, we exposed human Jurkat T cells to sodium cyanide in the presence or absence of iNOS inhibitors. We found that iNOS expression is necessary for hypoxia-induced lipid peroxidation and leukotriene B(4) generation. The inhibition of iNOS limited T-cell apoptosis by decreasing the activity of caspase-3 without affecting the expression of Fas/Apo-1/CD95 on the surface membrane of T cells. These data suggest iNOS-mediated NO produced endogenously in the T cell alters overall T-cell function and results in apoptosis. Proper control of iNOS expressed in the T cell may represent a useful approach to immunomodulation.
氰化钠诱导的化学性缺氧会引发一系列生化改变，导致包括T细胞在内的多种细胞类型发生凋亡。已知化学性缺氧通过激活其转录因子来促进诱导型一氧化氮合酶（iNOS）基因转录。为了确定iNOS和NO生成是否与化学性缺氧诱导的凋亡有关，我们在有或没有iNOS抑制剂的情况下，将人Jurkat T细胞暴露于氰化钠中。我们发现，iNOS表达对于缺氧诱导的脂质过氧化和白三烯B4生成是必需的。抑制iNOS通过降低caspase-3的活性来限制T细胞凋亡，而不影响T细胞膜表面Fas/Apo-1/CD95的表达。这些数据表明，T细胞内源性产生的iNOS介导的NO会改变T细胞的整体功能并导致凋亡。适当控制T细胞中表达的iNOS可能是一种有用的免疫调节方法。
