Vakhrusheva Tatyana V, Grigorieva Daria V, Gorudko Irina V, Sokolov Alexey V, Kostevich Valeria A, Lazarev Vassili N, Vasilyev Vadim B, Cherenkevich Sergey N, Panasenko Oleg M
a Federal Research and Clinical Center of Physical-Chemical Medicine, Federal Medical Biological Agency, Moscow, Russia.
b Belarusian State University, Minsk, Belarus.
Biochem Cell Biol. 2018 Oct;96(5):580-591. doi: 10.1139/bcb-2017-0292. Epub 2018 Feb 2.
Myeloperoxidase (MPO), found mainly in neutrophils, is released in inflammation. MPO produces reactive halogen species (RHS), which are bactericidal agents. However, RHS overproduction, i.e., halogenative stress, can also damage host biomolecules, and MPO itself may be targeted by RHS. Therefore, we examined the susceptibility of MPO to inactivation by its primary products (HOCl, HOBr, HOSCN) and secondary products such as taurine monochloramine (TauCl) and taurine monobromamine (TauBr). MPO was dose-dependently inhibited up to complete inactivity by treatment with HOCl or HOBr. TauBr diminished the activity but did not eliminate it. TauCl had no effect. MPO became inactivated when producing HOCl or HOBr but not HOSCN. Taurine protected MPO against inactivation when MPO was catalyzing oxidation of Cl to HOCl, whereas taurine failed to prevent inactivation when MPO was working with Br, either alone or in combination with Cl. SCN interfered with HOCl-mediated MPO inhibition. UV-vis spectra showed that heme degradation is involved in HOCl- and HOBr-mediated MPO inactivation. A negative linear correlation between the remaining chlorinating activity of HOCl- or HOBr-modified MPO and Escherichia coli survival upon incubation with MPO/HO/Cl was found. This study elucidated the possibility of MPO downregulation by MPO-derived RHS, which could counteract halogenative stress.
髓过氧化物酶（MPO）主要存在于中性粒细胞中，在炎症过程中释放。MPO产生反应性卤素物种（RHS），它们是杀菌剂。然而，RHS的过度产生，即卤化应激，也会损害宿主生物分子，并且MPO本身可能会成为RHS的作用靶点。因此，我们研究了MPO对其初级产物（次氯酸、次溴酸、硫氰酸）以及诸如单氯胺牛磺酸（TauCl）和单溴胺牛磺酸（TauBr）等次级产物失活的敏感性。用次氯酸或次溴酸处理后，MPO的活性呈剂量依赖性抑制，直至完全失活。TauBr降低了活性但并未消除它。TauCl没有作用。当产生次氯酸或次溴酸而不是硫氰酸时，MPO会失活。当MPO催化将Cl氧化为次氯酸时，牛磺酸可保护MPO免于失活；而当MPO单独或与Cl联合作用于Br时，牛磺酸无法阻止其失活。硫氰酸根干扰了次氯酸介导的MPO抑制作用。紫外可见光谱表明，血红素降解参与了次氯酸和次溴酸介导的MPO失活过程。在用MPO/HO/Cl孵育后发现次氯酸或次溴酸修饰的MPO的剩余氯化活性与大肠杆菌存活率之间呈负线性相关。本研究阐明了MPO衍生的RHS下调MPO的可能性，这可能会抵消卤化应激作用。
