کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5553581 | 1557956 | 2017 | 8 صفحه PDF | دانلود رایگان |

The isotonic substitution of extracellular chloride by gluconate (extracellular Clâ-free) has been demonstrated to elicit cardioprotection by attenuating ischaemia/reperfusion-induced elevation of intracellular chloride ion concentration ([Clâ]i). However, the downstream mechanism underlying the cardioprotective effect of extracellular Clâ-free is not fully established. Here, it was investigated whether extracellular Clâ-free attenuates mitochondrial dysfunction after hypoxia/reoxygenation (H/R) and whether mitochondrial permeability transition pore (mPTP) plays a key role in the extracellular Clâ-free cardioprotection. H9c2 cells were incubated with or without Clâ-free solution, in which Clâ was replaced with equimolar gluconate, during H/R. The involvement of mPTP was determined with atractyloside (Atr), a specific mPTP opener. The results showed that extracellular Clâ-free attenuated H/R-induced the elevation of [Clâ]i, accompanied by increase of cell viability and reduction of lactate dehydrogenase release. Moreover, extracellular Clâ-free inhibited mPTP opening, and improved mitochondria function, as indicated by preserved mitochondrial membrane potential and respiratory chain complex activities, decreased mitochondrial reactive oxygen species generation, and increased ATP content. Intriguingly, pharmacologically opening of the mPTP with Atr attenuated all the protective effects caused by extracellular Clâ-free, including suppression of mPTP opening, maintenance of mitochondrial membrane potential, and subsequent improvement of mitochondrial function. These results indicated that extracellular Clâ-free protects mitochondria from H/R injury in H9c2 cells and inhibition of mPTP opening is a crucial step in mediating the cardioprotection of extracellular Clâ-free.
Journal: Biomedicine & Pharmacotherapy - Volume 86, February 2017, Pages 637-644