Mason Katherine E, Stofan Daniel A
Division of Pediatric Critical Care, Department of Pediatrics, Case Western Reserve University, Mail Stop 6010, 11100 Euclid Avenue, Cleveland, OH 44120, USA.
Arch Biochem Biophys. 2008 Jan 15;469(2):151-6. doi: 10.1016/j.abb.2007.10.018. Epub 2007 Nov 1.
Sepsis impairs mitochondrial respiration but the mechanisms responsible are incompletely understood. We propose that Krebs cycle enzymes are inhibited in sepsis, contributing to reduced rates of oxidative phosphorylation.
The activities of Krebs cycle enzymes are decreased in endotoxemia and contribute to reduced rates of oxidative phosphorylation.
Adult male rats received an intraperitoneal injection of either endotoxin or saline. Cardiac mitochondria were subsequently isolated and measures of mitochondrial respiration and enzyme activities performed.
By 24h post endotoxin administration, there was a 28% reduction in mitochondrial respiration (P=0.0005) and a 24% reduction in aconitase activity (P=0.001). Functional activity of the electron transport chain was unaffected.
Our data demonstrate that in the heart, the administration of endotoxin significantly and selectively decreased aconitase activity in association with reduced rates of oxidative phosphorylation. We conclude that decreased activity of aconitase contributes to the endotoxin-stimulated reduction in mitochondrial respiration.
脓毒症会损害线粒体呼吸，但相关机制尚未完全明确。我们认为脓毒症时三羧酸循环酶受到抑制，导致氧化磷酸化速率降低。
内毒素血症时三羧酸循环酶的活性降低，导致氧化磷酸化速率降低。
成年雄性大鼠腹腔注射内毒素或生理盐水。随后分离心脏线粒体，检测线粒体呼吸和酶活性。
内毒素注射后24小时，线粒体呼吸降低28%（P=0.0005），乌头酸酶活性降低24%（P=0.001）。电子传递链的功能活性未受影响。
我们的数据表明，在心脏中，内毒素给药显著且选择性地降低乌头酸酶活性，同时氧化磷酸化速率降低。我们得出结论，乌头酸酶活性降低导致内毒素刺激的线粒体呼吸减少。
