XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta

Posters
5.
THE ROLE OF MAP-KINASE PATHWAY IN GLOBAL ISCHEMIA/
REPErfUSION INJURY OF raT BraIN afTER INDUCED
HYPERHOMOCYSTEINEMIA
Mária Kovalská 1 , Martina Pavlíková 1 , Zuzana Tatarková 1 , Peter Kaplán 1 ,
Dušan Dobrota 1 , Marian Adamkov 2 and Ján Lehotský 1
1
Department of Medical Biochemistry, 2 Department of Histology and Embryology
Comenius University, Jessenius Fac Med Martin
An altered cross-talk in intracellular signaling pathways is presumed in the mechanisms
in ischemic injury. The MAPK/ERK is a signal transduction route that couples intracellular
responses to cell surface receptors. ERK protein is part of the cascade leading to survival
of neurons after injury. Tolerance induced by preconditioning (IPC) is tissue adaptation
to sub-lethal ischemia. Hyperhomocysteinemia (hHcy) is one of the risk factor, which
could have negative impact on the onset/progression of ischemia/reperfusion injury
(IRI). In these experiments, we have studied changes in MAPK pathways and related
enzymes after global IRI in forebrain homogenate. In addition, the effects of: i) ischemic
preconditioning (IPC) and ii) hyperhomocysteinemia (hHcy) on IRI-associated alternations
of protein levels of MAPK pathway was determined. Global forebrain ischemia was
induced by 4-vessels occlusion. Rats were preconditioned by 5 min of sub-lethal ischemia
and 2 days later, 15 min of lethal ischemia with reperfusion period of 1h, 3h, 24h and
72h was induced. hHCy was induced by twice a day subcutaneous injection of homocysteine
(0.45 µmol/g). Immunohistochemical as well as Western blot analysis identified
MAPK/ERK protein in injured areas. The highest level of the protein was detected in the
reperfusion time after IPC. Converse effect was observed in the reperfusion time after
induced hHcy. This suggests that adaptive mechanisms in the MAPK signal transduction
machinery might have a potential role in tissues response subjected to IRI and in the
phenomenon of tolerance.
Acknowledgments: Supported by VEGA 0049/09, VVCE 0064/07, UK-16/2007 and
UK/10/2010.
XXII. Biochemistry Congress, Martin
119