کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2191107 | 1097847 | 2009 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Cardioprotection by metabolic shut-down and gradual wake-up Cardioprotection by metabolic shut-down and gradual wake-up](/preview/png/2191107.png)
Mitochondria play a critical role in cardiac function, and are also increasingly recognized as end effectors for various cardioprotective signaling pathways. Mitochondria use oxygen as a substrate, so by default their respiration is inhibited during hypoxia/ischemia. However, at reperfusion a surge of oxygen and metabolic substrates into the cell is thought to lead to rapid reestablishment of respiration, a burst of reactive oxygen species (ROS) generation and mitochondrial Ca2+ overload. Subsequently these events precipitate opening of the mitochondrial permeability transition (PT) pore, which leads to myocardial cell death and dysfunction. Given that mitochondrial respiration is already inhibited during hypoxia/ischemia, it is somewhat surprising that many respiratory inhibitors can improve recovery from ischemia-reperfusion (IR) injury. In addition ischemic preconditioning (IPC), in which short non-lethal cycles of IR can protect against subsequent prolonged IR injury, is known to lead to endogenous inhibition of several respiratory complexes and glycolysis. This has led to a hypothesis that the wash-out of inhibitors or reversal of endogenous inhibition at reperfusion may afford protection by facilitating a more gradual wake-up of mitochondrial function, thereby avoiding a burst of ROS and Ca2+ overload. This paper will review the evidence in support of this hypothesis, with a focus on inhibition of each of the mitochondrial respiratory complexes.
Journal: Journal of Molecular and Cellular Cardiology - Volume 46, Issue 6, June 2009, Pages 804–810