Mitophagy mediated effects of postconditioning and melatonin in cerebral ischemia-reperfusion injury

Mitophagy Mediated Effects Of Postconditioning And Melatonin In Cerebral Ischemia-Reperfusion Injury. Ischemic postconditioning (PostC) is a strong endogenous protective phenomenon, which targets the increased tolerance of the myocardium against injury when the tissue is subjected to short intervals of ischemia-reperfusion (IR) in reperfusion. Remote ischemic postconditioning (RePostC) is a noninvasive method that protects vital organs susceptible to ischemia by measures in remote organs. Melatonin released from the pineal gland is a hormone that plays an important role in reducing cerebral injury. Mitophagy is a type of autophagy that removes damaged mitochondria to protect the cell. In this study, it was aimed to investigate the effects of PostC, RePostC and melatonin on the expression levels of cerebral injury markers BNP; Parkin-PINK1, BNIP3 and FUNDC1 proteins involved in mitophagy in cerebral IR damage. Rats were divided into 5 groups (n: 10). PostC was performed as three sessions as ischemia for 10 sec and reperfusion for 30 sec. RePostC underwent sequential I/R of the right hind limb, using 3 cycles of 5 min of ischemia and 5 min of reperfusion following MCA reperfusion. Melatonin was administered as a single dose at the beginning of reperfusion. Protein expression levels were determined with Western Blot; Open field, vertical pole and beam walking tests were performed for motor coordination analysis. Besides that, DAPI staining was applied to detect neuronal viability. BNP, Parkin-PINK1, BNIP3 and FUNDC1 levels increased with IR injury. In treatment groups, Parkin and PINK1 levels did not change, while BNP, FUNDC1 and BNIP3 levels decreased when compared to IR group. In the behavioral tests, the locomotor activity decreased significantly with IR but it did not change statistically with treatments. As a result; PostC, RePostC and melatonin may provide protection by inhibiting mitophagy through the FUNDC1 and BNIP3. Increased levels of BNP due to cerebral IR injury may be used as biomarkers in the diagnosis and treatment of IR injury. Melatonin, which procures protection with similar mechanisms to postconditioning, may be a pharmacological conditioning agent. Keywords: Postconditioning, melatonin, mitophagy, BNIP3, FUNDC1