TNF-induced mitochondrial damage: a link between mitochondrial complex I activity and left ventricular dysfunction.
TNF-induced mitochondrial damage: a link between mitochondrial complex I activity and left ventricular dysfunction.
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DOI：
10.1016/j.freeradbiomed.2008.10.049
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发表时间：
2009-02-15
影响因子：
7.4
通讯作者：
Francis, Joseph
中科院分区：
文献类型：
--
作者：
Mariappan, Nithya;Elks, Carrie M.;Fink, Bruno;Francis, Joseph
线粒体损伤与心脏病的进展有关。大量证据表明促炎细胞因子会诱发氧化应激并导致心脏功能障碍。本研究旨在确定 TNF 诱导的超氧化物 ( ) 增加是否通过损害呼吸复合物 I 活性而导致左心室 (LV) 线粒体损伤。我们采用电子顺磁共振（EPR）方法，使用氧标记来测量线粒体呼吸复合物的耗氧量。成年雄性 Sprague-Dawley 大鼠被分为四组：对照组、TNF 治疗组（腹腔注射）、TNF+ 夹竹桃麻素（APO；200 μmol/kg bw，口服）和 TNF+ Tempol（Temp；300 μmol/kg bw，口服）。每天注射TNF，持续5天。处死大鼠，收集左心室组织，并分离线粒体用于 EPR 研究。 TNF 动物的 LV ROS 总产量显着高于对照组； APO 或 Temp 治疗改善了 TNF 诱导的 LV ROS 产生。 TNF 和 TNF+ APO 组的线粒体总 ROS 产量显着高于对照组和 TNF+ Temp 组。这些发现表明，TNF 改变细胞氧化还原状态，通过增加线粒体产量和消耗 ATP 合成来减少四个复合物 I 亚基的表达，并减少耗氧量，从而导致线粒体损伤并导致左心室功能障碍。
Mitochondrial damage is implicated in the progression of cardiac disease. Considerable evidence suggests that proinflammatory cytokines induce oxidative stress and contribute to cardiac dysfunction. This study was conducted to determine whether a TNF-induced increase in superoxide ( ) contributes to mitochondrial damage in the left ventricle (LV) by impairing respiratory complex I activity. We employed an electron paramagnetic resonance (EPR) method to measure and oxygen consumption in mitochondrial respiratory complexes, using an oxygen label. Adult male Sprague–Dawley rats were divided into four groups: control, TNF treatment (ip), TNF+ apocynin (APO; 200 μmol/kg bw, orally), and TNF+ Tempol (Temp; 300 μmol/kg bw, orally). TNF was injected daily for 5 days. Rats were sacrificed, LV tissue was collected, and mitochondria were isolated for EPR studies. Total LV ROS production was significantly higher in TNF animals than in controls; APO or Temp treatment ameliorated TNF-induced LV ROS production. Total mitochondrial ROS production was significantly higher in the TNF and TNF+ APO groups than in the control and TNF+ Temp groups. These findings suggest that TNF alters the cellular redox state, reduces the expression of four complex I subunits by increasing mitochondrial production and depleting ATP synthesis, and decreases oxygen consumption, thereby resulting in mitochondrial damage and leading to LV dysfunction.
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DOI：
10.1152/ajpheart.00036.2004
发表时间：
2004-10-01
影响因子：
4.8
作者：
Moe, GW;Marin-Garcia, J;Feng, QP
通讯作者：
Feng, QP
影响因子：
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作者：
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Dikalov, S
DOI：
10.1152/ajpheart.00286.2007
发表时间：
2007-07-01
影响因子：
4.8
作者：
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通讯作者：
Francis, Joseph
影响因子：
8.3
作者：
Lopez-Campistrous, Ana;Hao, Li;Fernandez-Patron, Carlos
通讯作者：
Fernandez-Patron, Carlos
影响因子：
10.8
作者：
Kang, Yu-Ming;Ma, Ying;Francis, Joseph
通讯作者：
Francis, Joseph