title: Ischemia/Reperfusion-Induced Translocation of PKCβII to Mitochondria as an Important Mediator of a Protective Signaling Mechanism in an Ischemia-Resistant Region of the Hippocampus.
abstract: Emerging reports indicate that activated PKC isoforms that translocate to the mitochondria are pro- or anti-apoptotic to mitochondrial function. Here, we concentrate on the role of PKCβ translocated to mitochondria in relation to the fate of neurons following cerebral ischemia. As we have demonstrated previously ischemia/reperfusion injury (I/R) results in translocation of PKCβ from cytoplasm to mitochondria, but only in ischemia-resistant regions of the hippocampus (CA2-4, DG), we hypothesize that this translocation may be a mediator of a protective signaling mechanism in this region. We have therefore sought to demonstrate a possible relationship between PKCβII translocation and ischemic resistance of CA2-4, DG. Here, we reveal that I/R injury induces a marked elevation of PKCβII protein levels, and consequent enzymatic activity, in CA2-4, DG in the mitochondrial fraction. Moreover, the administration of an isozyme-selective PKCβII inhibitor showed inhibition of I/R-induced translocation of PKCβII to the mitochondria and an increase in neuronal death following I/R injury in CA1 and CA2-4, DG in both an in vivo and an in vitro model of ischemia. The present results suggest that PKCβII translocated to mitochondria is involved in providing ischemic resistance of CA2-4, DG. However, the exact mechanisms by which PKCβII-mediated neuroprotection is achieved are in need of further elucidation.
authors.affiliation: Molecular Biology Unit, Mossakowski Medical Research Centre, PAS, Warsaw, Poland.
authors.forename: Olga
authors.initials: O
authors.lastname: Krupska
authors.affiliation: Stem Cell Bioengineering Unit, Mossakowski Medical Research Centre, PAS, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Sarnowska
authors.affiliation: Faculty of Chemistry, University of Warsaw, Warsaw, Poland.
authors.forename: Bartlomiej
authors.initials: B
authors.lastname: Fedorczyk
authors.affiliation: Electron Microscopy Platform, Mossakowski Medical Research Centre, PAS, Warsaw, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Gewartowska
authors.affiliation: Faculty of Chemistry, University of Warsaw, Warsaw, Poland.|Department of Neuropeptides, Mossakowski Medical Research Centre, PAS, Warsaw, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Misicka
authors.affiliation: Molecular Biology Unit, Mossakowski Medical Research Centre, PAS, Warsaw, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Zablocka
authors.affiliation: Molecular Biology Unit, Mossakowski Medical Research Centre, PAS, Warsaw, Poland. mberesewicz@imdik.pan.pl.
authors.forename: Malgorzata
authors.identifier: http://orcid.org/0000-0002-2204-5184
authors.initials: M
authors.lastname: Beresewicz
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D005849:Gerbillinae; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D009924:Organ Culture Techniques; D064546:Protein Kinase C beta / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D064546:Protein Kinase C beta
keywords: Cerebral ischemia; Endogenous neuroprotection; Mitochondria; PKCβII; Protein kinase C