Peroxisome proliferator-activated receptor-gamma dependent pathway reduces the phosphorylation of dynamin-related protein 1 and ameliorates hippocampal injury induced by global ischemia in rats

Background: dynamin-related protein 1 (drp1) is a mitochondrial fission protein that,upon phosphorylation at serine 616 (p-drp1(ser616)),plays a pivotal role in neuronal death after ischemia. in the present study,we hypothesized that peroxisome proliferator-activated receptor-gamma (pparγ)-dependent pathway can reduce the expression of p-drp1(ser616) and ameliorate hippocampal injury induced by global ischemia in rats. results: we found that pretreatment of the rats with mdivi-1,a selective drp1 inhibitor,decreased the level of transient global ischemia (tgi)-induced p-drp1(ser616) and reduced cellular contents of oxidized proteins,activated caspase-3 expression as well as the extent of dna fragmentation. delivery of sirna against drp1 attenuated the expression of p-drp1(ser616) that was accompanied by alleviation of the tgi-induced protein oxidation,activated caspase-3 expression and dna fragmentation in hippocampal proteins. exogenous application of pioglitazone,a pparγ agonist,reduced the p-drp1(ser616) expression,decreased tgi-induced oxidative stress and activated caspase-3 expression,lessened the extents of dna fragmentation,and diminished the numbers of tunel-positive neuronal cells; all of these effects were reversed by gw9662,a pparγ antagonist. conclusions: our findings thus indicated that inhibition of tgi-induced p-drp1(ser616) expression by drp1 inhibitor and drp1-sirna can decrease protein oxidation,activated caspase-3 expression and neuronal damage in the hippocampal ca1 subfield. pparγ agonist,through pparγ-dependent mechanism and via decreasing p-drp1(ser616) expression,can exert anti-oxidative and anti-apoptotic effects against ischemic neuronal injury. © 2016 chuang et al.