On from the TGI-induced protein oxidation, activated caspase-3 expression and DNA fragmentation in hippocampal proteins. Exogenous application of pioglitazone, a PPAR agonist, lowered the p-Drp1(Ser616) expression, decreased TGI-induced oxidative tension 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 PPAR antagonist. Conclusions: Our findings hence indicated that inhibition of TGI-induced p-Drp1(Ser616) expression by Drp1 inhibitor and Drp1-siRNA can lower protein oxidation, activated caspase-3 expression and neuronal damage in the hippocampal CA1 subfield. PPAR agonist, by way of PPAR-dependent mechanism and by way of decreasing p-Drp1(Ser616) expression, can exert anti-oxidative and anti-apoptotic effects against ischemic neuronal injury. Keyword phrases: Apoptosis, Dynamin-related protein 1, International ischemia, Hippocampus, Peroxisome proliferator-activated receptor-gamma, Pioglitazone* Correspondence: [email protected] Equal contributors 1 Division of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan two Center for Translational Study in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan Complete list of author facts is obtainable at the end of your article2016 Chuang et al. Open Access This article is distributed under the terms with the Creative Commons Attribution four.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, offered you give acceptable credit to the original author(s) and the source, deliver a link towards the Creative Commons license, and indicate if alterations have been created.ER alpha/ESR1, Human (His) The Creative Commons Public Domain Dedication waiver (http://creativecommons.DKK-1 Protein Gene ID org/publicdomain/zero/1.0/) applies to the data made readily available in this short article, unless otherwise stated.Chuang et al. Journal of Biomedical Science (2016) 23:Page two ofBackground Mitochondria would be the powerhouses of cells to generate ATP too as to regulate signaling cascades, like apoptosis [1]. A recent progress towards the understanding of mitochondrial control over apoptosis may be the discovery of a drastic morphological adjust of this organelle under stressful circumstances [2, 3].PMID:24518703 Mitochondria are dynamic organelles that keep their shape or morphology through two opposing processes: fission and fusion [4]. Although the fission process entails the constriction and cleavage of mitochondria, fusion approach requires the lengthening of mitochondria by tethering and joining two adjacent mitochondria together [4]. It was shown that, just before the apoptotic processes, mitochondria fragment into many compact units (fission) and blocking mitochondrial fission can inhibit cytochrome c release with delayed cell death [2]. Drp1, a vital fission protein, plays a crucial part in focal cerebral ischemia and inhibition of Drp1 can decrease the infarct volumes [7]. Expression of the dominantnegative Drp1 mutant in cell lines decreases mitochondrial fragmentation and blocks cell death in response to various apoptotic insults [10, 11]. A selective neuronal loss in hippocampal CA1 subfield is often a histological hallmark of transient international ischemia (TGI) and reperfusion [12, 13]. This condition occurs in individuals with anoxic-ischemic encephalopathy and cardiorespiratory arrest of different.