Alkyl hydroperoxide reductase subunit C (AhpC) protects bacterial and human cells against reactive nitrogen intermediates

Alkyl hydroperoxide reductase subunit C (AhpC) protects bacterial and human cells against reactive nitrogen intermediates
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DOI:
10.1016/s1097-2765(00)80079-9
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发表时间:
1998-05-01
期刊:
影响因子:
16
通讯作者:
Nathan, C
Nathan, C
中科院分区:
生物学1区
文献类型:
--
作者:
Chen, L;Xie, QW;Nathan, C

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在鼠伤寒沙门氏菌中,ahpC编码烷基过氧化氢还原酶的C亚基,这是一种还原有机过氧化物的酶。在这里,我们问ahpC是否可以保护细胞免受活性氮中间体(RNI)的影响。在ahpC中破坏的沙门氏菌对RNI变得超敏,来自结核分枝杆菌或鼠伤寒沙门氏菌的ahpC完全弥补了这一缺陷。不同于对异丙苯过氧化氢的保护,ahpC对RNI的保护是独立于还原黄素蛋白AhpF的。分枝杆菌ahpC可保护外源性或内源性转染型一氧化氮合酶产生的RNI引起的细胞坏死和凋亡。对RNI的抵抗似乎是ahpC的一种生理功能。AhpC是已知分布最广泛的基因,它直接保护细胞免受RNI的影响,并提供对抗结核免疫元件的酶防御。
In Salmonella typhimurium, ahpC encodes subunit C of alkyl hydroperoxide reductase, an enzyme that reduces organic peroxides. Here, we asked if ahpC could protect cells from reactive nitrogen intermediates (RNI). Salmonella disrupted in ahpC became hypersusceptible to RNI, ahpC from either Mycobacterium tuberculosis or S. typhimurium fully complemented the defect. Unlike protection against cumene hydroperoxide, protection afforded by ahpC against RNI was independent of the reducing flavoprotein, AhpF. Mycobacterial ahpC protected human cells from necrosis and apoptosis caused by RNI delivered exogenously or produced endogenously by transfected nitric oxide synthase. Resistance to RNI appears to be a physiologic function of ahpC. ahpC is the most widely distributed gene known that protects cells directly from RNI, and provides an enzymatic defense against an element of antitubercular immunity.