Contributor:

Zabłocka, Barbara (Promotor)

Publisher:

Instytut Medycyny Doswiadczalnej i Klinicznej im. M. Mossakowskiego PAN

Place of publishing:

Warszawa

Description:

Bibliogr. zawiera 256 pozycji ; 116 s.: il., fot., tabl.; 30 cm

Degree name:

doktor

Level of degree:

2

Type of object:

Thesis

Abstract:

Exitence of brain areas less sensitive to ischemia (such as CA2-4, DG region of hippocampus) offers hope for development of an ischemia effects treatment based on enhancement of endogenous adaptive response nervous cells. The variety of proteins, including protein kinases C (PKC) translocate to mitochondria following ischemia-reperfusion (I/R), which may lead to cell death or its survival. The aim of the study was to verify PKCbeta engagement in endogenous neuroprotection in CA2-4, DG region of hippocampus after I/R and to discover its mechanisms in mitochondria. Two experimental models were used: an in vivo-5-min. ischemia of gerbil brain and an in w=vitro-exitotoxicity evoked in organotypic hippocampal slice culture. Presented results show that immunoractivity and activity of PKCbeta increased in mitochondria of CA2-4, DG following I/R. A specific, peptide-inhibitor of PKCbetaII decreased postischemic translocation of the kinase to mitochondria and enhanced injury of neurons caused by I/R or excitotoxicityin the experimental models. What is more, PKCbeta II located inmitochondrial matrix after I/R.Due to this fact it was studied that PKCbeta II may interact with mitochondrial proteins (such as ATPase, pyruvate dehydrogenase, glutaminase0. Preliminary metabolomics results suggested changes in energy metabolism, mainly pyruvate alternations in CA2-4, DG region in which PKCbeta II may be engaged. Presented research indicates thatPKCbeta II translocation to mitochondria is an element of endogenous neuroprotection in the region of hippocampus less prone to I/R ( CA2-4, DG). Further development of research regarding neuroprotective mechanism of PKCbetaII can reveal new molecular factors, which may become targets of pharmacological treatment imtendent for patients sufferin from braim ischemia.

Relation:

Prace doktorskie.

Format:

application/pdf

Resource Identifier:

oai:rcin.org.pl:72010

Source:

INDiK PAN, coll no. ZS 395 ; click here to follow the link

Rights:

Creative Commons Attribution BY 4.0 license

Terms of use:

Copyright-protected material. [CC BY 4.0] May be used within the scope specified in Creative Commons Attribution BY 4.0 license, full text available at: ; -

Digitizing institution:

Instytut Medycyny Doświadczalnej i Klinicznej im. M. Mossakowskiego Polskiej Akademii Nauk

Original in:

Library of the Mossakowski Medical Research Institute PAS

Projects co-financed by:

Operational Program Digital Poland, 2014-2020, Measure 2.3: Digital accessibility and usefulness of public sector information; funds from the European Regional Development Fund and national co-financing from the state budget.

Access:

Open