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

Krupska O1, Sarnowska A2, Fedorczyk B3, Gewartowska M4, Misicka A3,5, Zablocka B1, Beresewicz M6.

 

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.

 

1 Molecular Biology Unit, Mossakowski Medical Research Centre, PAS, Warsaw, Poland.

2 Stem Cell Bioengineering Unit, Mossakowski Medical Research Centre, PAS, Warsaw, Poland.

3 Faculty of Chemistry, University of Warsaw, Warsaw, Poland.

4 Electron Microscopy Platform, Mossakowski Medical Research Centre, PAS, Warsaw, Poland.

5 Department of Neuropeptides, Mossakowski Medical Research Centre, PAS, Warsaw, Poland.

6 Molecular Biology Unit, Mossakowski Medical Research Centre, PAS, Warsaw, Poland. Ten adres pocztowy jest chroniony przed spamowaniem. Aby go zobaczyć, konieczne jest włączenie w przeglądarce obsługi JavaScript..

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.

KEYWORDS:

Cerebral ischemia; Endogenous neuroprotection; Mitochondria; PKCβII; Protein kinase C

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