Targeting Mitochondrial Dysfunction with L-Alpha Glycerylphosphorylcholine.
Targeting Mitochondrial Dysfunction with L-Alpha Glycerylphosphorylcholine.
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DOI：
10.1371/journal.pone.0166682
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Hartmann P
中科院分区：
文献类型：
--
作者：
Strifler G;Tuboly E;Görbe A;Boros M;Pécz D;Hartmann P
我们推测，L-α-甘油磷酸胆碱（GPC），脱酰磷脂酰胆碱衍生物，可以影响线粒体呼吸活动，并通过这种方式，可能发挥组织保护作用。用高分辨呼吸仪检测大鼠肝线粒体，分析GPC对常氧和缺氧条件下线粒体电子传递链的影响。此外，Sprague-Dawley大鼠进行假手术或标准化肝脏缺血再灌注（IR），有或没有GPC的管理。测定还原型谷胱甘肽（GSH）、氧化型谷胱甘肽二硫化物（GSSG）、组织髓过氧化物酶、黄嘌呤氧化还原酶和NADPH氧化酶活性。组织丙二醛和亚硝酸盐/硝酸盐的形成，以及血液超氧化物和过氧化氢的生产进行了评估。GPC增加了复合物I-连接的线粒体氧消耗的功效，具有显著较低的体外漏呼吸。从机制上讲，肝脏IR损伤伴随着线粒体呼吸恶化和ROS产生增加，因此，炎症酶活性显着增加。GPC给药降低了炎症活化，与氧化和亚硝化应激标志物的降低一致。GPC通过保护线粒体复合物I功能呼吸，减少IR发作后氧化应激的生化体征。这表明GPC是一种靶向化合物，间接抑制主要细胞内超氧化物生成酶的活性。
We hypothesized that L-alpha-glycerylphosphorylcholine (GPC), a deacylatedphosphatidylcholine derivative, can influence the mitochondrial respiratory activity and in this way, may exert tissue protective effects. Rat liver mitochondria were examined with high-resolution respirometry to analyze the effects of GPC on the electron transport chain in normoxic and anoxic conditions. Besides, Sprague-Dawley rats were subjected to sham operation or standardized liver ischemia-reperfusion (IR), with or without GPC administration. The reduced glutathione (GSH) and oxidized glutathione disulfide (GSSG), the tissue myeloperoxidase, xanthine oxidoreductase and NADPH oxidases activities were measured. Tissue malondialdehyde and nitrite/nitrate formation, together with blood superoxide and hydrogen-peroxide production were assessed. GPC increased the efficacy of complex I-linked mitochondrial oxygen consumption, with significantly lower in vitro leak respiration. Mechanistically, liver IR injury was accompanied by deteriorated mitochondrial respiration and enhanced ROS production and, as a consequence, by significantly increased inflammatory enzyme activities. GPC administration decreased the inflammatory activation in line with the reduced oxidative and nitrosative stress markers. GPC, by preserving the mitochondrial complex I function respiration, reduced the biochemical signs of oxidative stress after an IR episode. This suggests that GPC is a mitochondria-targeted compound that indirectly suppresses the activity of major intracellular superoxide-generating enzymes.
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影响因子：
2.9
作者：
Chen C;Hyun TK;Han X;Feng Z;Li Y;Liu X;Liu J
通讯作者：
Liu J
DOI：
10.1152/ajpgi.00400.2002
发表时间：
2003-03-01
影响因子：
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作者：
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通讯作者：
Grisham, MB
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10.1152/ajpheart.00052.2010
发表时间：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
3.7
作者：
Habersetzer J;Larrieu I;Priault M;Salin B;Rossignol R;Brèthes D;Paumard P
通讯作者：
Paumard P