TNFα protects cardiac mitochondria independently of its cell surface receptors.
TNFα protects cardiac mitochondria independently of its cell surface receptors.
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TNFα独立于其细胞表面受体保护心脏线粒体。
DOI：
10.1007/s00395-010-0113-4
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发表时间：
2010-11
影响因子：
9.5
通讯作者：
Lecour S
中科院分区：
文献类型：
--
作者：
Lacerda L;McCarthy J;Mungly SF;Lynn EG;Sack MN;Opie LH;Lecour S
我们的新建议是TNFα对心脏线粒体呼吸功能产生直接影响，而不依赖于其细胞表面受体。已知TNFα诱导的心脏保护作用涉及活性氧（ROS）和鞘脂。因此，我们进一步提出，这种直接的线粒体效应是通过ROS和鞘脂介导的。将保护浓度的TNFα（0.5 ng/ml）加入到来自黑色6 × 129小鼠（WT）和双TNF受体敲除小鼠（TNFR 1&2 −/−）的分离心脏线粒体中。在存在/不存在两种抗氧化剂N-乙酰基-L-半胱氨酸或N-叔丁基-α-（2-磺基苯基）硝酮或两种鞘脂途径拮抗剂N-油酰乙醇胺（NOE）或丙咪嗪的情况下分析呼吸参数和线粒体内膜电位。在WT中，与对照组相比，TNFα将状态3呼吸从279.3 ± 3降低至119.3 ± 2（nmol O2/mg蛋白质/min），将质子漏从15.7 ± 0.6%（对照）增加至36.6 ± 4.4%，并将膜电位降低20.5 ± 3.1%。在TNFR 1&2 −/−小鼠中，TNFα将状态3呼吸从205.2 ± 4降低至75.7 ± 1（与相应对照组相比p < 0.05）。在WT小鼠中，添加TNFα的两种抗氧化剂分别将状态3呼吸恢复至269.2 ± 2和257.6 ± 2。丙咪嗪和NOE也分别将状态3呼吸恢复至248.4 ± 2和249.0 ± 2（p < 0.01，与TNFα单独给药相比）。类似地，抗氧化剂和鞘脂途径抑制剂均将质子泄漏恢复至TNF前值。TNFα处理的线粒体或分离的心肌纤维在缺氧-复氧后显示呼吸增加，但在抗氧化剂或NOE存在下，这种作用消失。在TNFR 1&2 −/−小鼠中获得了类似的数据。TNFα对缺氧-复氧损伤的离体线粒体呼吸功能具有保护作用。这种作用似乎不依赖于其细胞表面受体，但可能是由ROS和鞘脂介导的。
Our novel proposal is that TNFα exerts a direct effect on mitochondrial respiratory function in the heart, independently of its cell surface receptors. TNFα-induced cardioprotection is known to involve reactive oxygen species (ROS) and sphingolipids. We therefore further propose that this direct mitochondrial effect is mediated via ROS and sphingolipids. The protective concentration of TNFα (0.5 ng/ml) was added to isolated heart mitochondria from black 6 × 129 mice (WT) and double TNF receptor knockout mice (TNFR1&2−/−). Respiratory parameters and inner mitochondrial membrane potential were analyzed in the presence/absence of two antioxidants, N-acetyl-l-cysteine or N-tert-butyl-α-(2-sulfophenyl)nitrone or two antagonists of the sphingolipid pathway, N-oleoylethanolamine (NOE) or imipramine. In WT, TNFα reduced State 3 respiration from 279.3 ± 3 to 119.3 ± 2 (nmol O2/mg protein/min), increased proton leak from 15.7 ± 0.6% (control) to 36.6 ± 4.4%, and decreased membrane potential by 20.5 ± 3.1% compared to control groups. In TNFR1&2−/− mice, TNFα reduced State 3 respiration from 205.2 ± 4 to 75.7 ± 1 (p < 0.05 vs. respective control). In WT mice, both antioxidants added with TNFα restored State 3 respiration to 269.2 ± 2 and 257.6 ± 2, respectively. Imipramine and NOE also restored State 3 respiration to 248.4 ± 2 and 249.0 ± 2, respectively (p < 0.01 vs. TNFα alone). Similarly, both antioxidant and inhibitors of the sphingolipid pathway restored the proton leak to pre-TNF values. TNFα-treated mitochondria or isolated cardiac muscle fibers showed an increase in respiration after anoxia–reoxygenation, but this effect was lost in the presence of an antioxidant or NOE. Similar data were obtained in TNFR1&2−/− mice. TNFα exerts a protective effect on respiratory function in isolated mitochondria subjected to an anoxia–reoxygenation insult. This effect appears to be independent of its cell surface receptors, but is likely to be mediated by ROS and sphingolipids.
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影响因子：
9.5
作者：
Baines CP
通讯作者：
Baines CP
影响因子：
10.8
作者：
Lacerda, Lydia;Somers, Sarin;Lecour, Sandrine
通讯作者：
Lecour, Sandrine
影响因子：
37.8
作者：
Lecour, S;Suleman, N;Opie, LH
通讯作者：
Opie, LH
DOI：
10.1165/ajrcmb.24.6.4228
发表时间：
2001-06-01
影响因子：
6.4
作者：
Corda, S;Laplace, C;Duranteau, J
通讯作者：
Duranteau, J
影响因子：
6.1
作者：
Lacerda, Lydia;Smith, Robert M.;Lecour, Sandrine
通讯作者：
Lecour, Sandrine