Functional interactions between complex I and complex II with nNOS in regulating cardiac mitochondrial activity in sham and hypertensive rat hearts.
Functional interactions between complex I and complex II with nNOS in regulating cardiac mitochondrial activity in sham and hypertensive rat hearts.
复制标题
复合物 I 和复合物 II 与 nNOS 之间的功能相互作用在调节假心脏和高血压大鼠心脏中的心肌线粒体活性中。
DOI：
10.1007/s00424-020-02458-2
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Yin Hua Zhang
中科院分区：
文献类型：
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作者：
Yu Na Wu;Vidya K Sudarshan;Shi Chao Zhu;Yong Feng Shao;Sung Joon Kim;Yin Hua Zhang
一氧化氮（NO）通过与复合物的相互作用影响线粒体活性。在这里，我们调查的法规复杂的I（C-I）和复杂的II（C-II）的神经元型一氧化氮合酶（nNOS）的存在下，脂肪酸补充剂和左心室（LV）线粒体活性的影响假手术和血管紧张素II（Ang-II）诱导的高血压（HTN）大鼠。我们的结果表明，nNOS蛋白表达在假手术和HTN LV线粒体富集部分。在假手术组，棕榈酸（PA）或棕榈酰肉碱（PC）可增加氧耗率（OCR）和细胞内ATP。nNOS抑制剂S-甲基-L-硫代瓜氨酸（SMTC）对PA或PC引起的OCR或细胞ATP增加无影响。然而，SMTC增加了PA +丙二酸盐（C-II抑制剂）的OCR，但不增加PA +鱼藤酮（C-I抑制剂）的OCR，表明nNOS在补充脂肪酸的情况下减弱C-I。的确，SMTC增加C-I活性，但不增加C-II活性。相反，在LV心肌细胞中，鱼藤酮+ PA增加nNOS衍生的NO。在HTN中，PC使C-I活性增加，但使C-II活性降低，从而使OCR降低。SMTC使PC的C-I和C-II活性增加，导致线粒体OCR增强。值得注意的是，SMTC仅用鱼藤酮增加OCR，表明nNOS调节HTN中C-II介导的OCR。丙二酸+ PA可部分降低nNOS源性NO。总之，在假手术中脂肪酸存在下，nNOS减弱C-I介导的线粒体OCR，C-I调节nNOS活性。在HTN中，nNOS减弱C-I和C-II活性，而nNOS和C-II之间的相互作用维持线粒体活性。
Nitric oxide (NO) affects mitochondrial activity through its interactions with complexes. Here, we investigated regulations of complex I (C-I) and complex II (C-II) by neuronal NO synthase (nNOS) in the presence of fatty acid supplementation and the impact on left ventricular (LV) mitochondrial activity from sham and angiotensin II (Ang-II)-induced hypertensive (HTN) rats. Our results showed that nNOS protein was expressed in sham and HTN LV mitochondrial enriched fraction. In sham, oxygen consumption rate (OCR) and intracellular ATP were increased by palmitic acid (PA) or palmitoyl-carnitine (PC). nNOS inhibitor, S-methyl-l-thiocitrulline (SMTC), did not affect OCR or cellular ATP increment by PA or PC. However, SMTC increased OCR with PA + malonate (a C-II inhibitor), but not with PA + rotenone (a C-I inhibitor), indicating that nNOS attenuates C-I with fatty acid supplementation. Indeed, SMTC increased C-I activity but not that of C-II. Conversely, nNOS-derived NO was increased by rotenone + PA in LV myocytes. In HTN, PC increased the activity of C-I but reduced that of C-II, consequently OCR was reduced. SMTC increased both C-I and C-II activities with PC, resulted in OCR enhancement in the mitochondria. Notably, SMTC increased OCR only with rotenone, suggesting that nNOS modulates C-II-mediated OCR in HTN. nNOS-derived NO was partially reduced by malonate + PA. Taken together, nNOS attenuates C-I-mediated mitochondrial OCR in the presence of fatty acid in sham and C-I modulates nNOS activity. In HTN, nNOS attenuates C-I and C-II activities whereas interactions between nNOS and C-II maintain mitochondrial activity.