Effects of nitric oxide on mitochondrial permeability transition pore and thiol-mediated responses in cardiac myocytes
Effects of nitric oxide on mitochondrial permeability transition pore and thiol-mediated responses in cardiac myocytes
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DOI：
10.1016/j.niox.2011.12.007
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发表时间：
2012-02-15
影响因子：
3.9
通讯作者：
Hayashi, Hideharu
中科院分区：
文献类型：
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作者：
Ohtani, Hayato;Katoh, Hideki;Hayashi, Hideharu
一氧化氮 (NO) 改变线粒体通透性转换孔 (mPTP) 的开放。然而，NO 在 mPTP 上的信号通路仍然难以捉摸。我们的目的是阐明硫醇介导的反应对 NO 对透化肌细胞中 mPTP 的影响的贡献。我们发现（1）高浓度的精胺 NONOate（NO 供体；500 mu M）打开 mPTP 并使 Delta Psi(m) 去极化。 (2)低浓度的NONOate(5μM)阻止白术苷(一种mPTP开放剂)诱导的mPTP开放。 (3)Mn(III)四(4-苯甲酸)卟啉(Mn-TBAP、ONOO-清除剂)减弱高浓度NONOate对mPTP开放的作用，但不抑制低浓度NONOate的预防作用。 (4)当N-乙基马来酰亚胺抑制NO与硫醇的相互作用时，NONOate对mPTP的开放(高浓度NONOate)和预防作用(低浓度NONOate)被阻断。 (5)二硫苏糖醇（二硫键形成抑制剂）阻止高浓度NONOate诱导的mPTP开放。 (6)抗坏血酸(S-亚硝基化抑制剂)阻止低浓度NONOate对mPTP的预防作用。我们得出结论，高浓度NO对mPTP的打开与二硫键的形成和ONOO-的氧化作用有关。相反，生理浓度的NO对mPTP的抑制作用与S-亚硝基化有关。 (c) 2012 Elsevier Inc. 保留所有权利。
Nitric oxide (NO) alters the opening of mitochondrial permeability transition pore (mPTP). However, the signaling pathways of NO on mPTP remain elusive. We aimed to clarify the contribution of thiol-mediated responses to the effects of NO on mPTP in permeabilized myocytes. We found that (1) a high concentration of spermine NONOate (an NO donor; 500 mu M) opened mPTP and depolarized Delta Psi(m). (2) A low concentration of NONOate (5 mu M) prevented atractyloside (an mPTP opener)-induced mPTP opening. (3) Mn(III) tetrakis (4-benzoic acid) porphyrin (Mn-TBAP, ONOO- scavenger) attenuated the effect of high-concentration NONOate on mPTP opening, but did not inhibited the preventive effects of low-concentration NONOate. (4) When the interaction of NO with thiol was inhibited by N-ethylmaleimide, the opening (by high-concentration NONOate) and preventive effects (by low-concentration NONOate) of NONOate on mPTP were blocked. (5) Dithiothreitol (an inhibitor of disulfide bonds formation) prevented high-concentration NONOate-induced mPTP opening. (6) Ascorbic acid (an inhibitor of S-nitrosylation) prevented the preventive effects of low-concentration NONOate on mPTP. We conclude that opening of mPTP by high-concentration NO is related to disulfide bonds formation and oxidizing effects of ONOO-. In contrast, the inhibitory effect of physiological concentrations of NO on mPTP is related to S-nitrosylation. (c) 2012 Elsevier Inc. All rights reserved.