XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta

Lectures
PROCESSING OF AMYLOID PRECURSOR PROTEIN afTER
IN VIVO INDUCED ISCHEMIA
Eva Babušíková 1 , Dušan Dobrota 1 , Anthony J. Turner 2 and Natalia N. Nalivaeva 2
1
Department of Medical Biochemistry, Comenius University in Bratislava, Jessenius
Faculty of Medicine in Martin, Martin, Slovakia, 2 Institute of Molecular and Cellular
Biology, University of Leeds, Leeds, United Kingdom
Ischemia stroke results from a transient or permanent reduction in cerebral blood flow.
In recent years it has been suggested that neurological disorder in elderly human population
as Alzheimer’s disease (AD) is linked to certain brain pathologies, which promote its
development and progression via accumulation of toxic amyloid peptide (Aβ) deposits
in the brain. In the present study we determined the effect of the global ischemia (the
four-vessel occlusion model) on the amount of amyloid precursor protein (APP) and
some amyloid peptide degrading metalloproteinases. We observed that ischemia result
in increased amyloidogenic processing of APP in hippocampus and cortex as well. Levels
of APP increased significantly after ischemia as well as the amount of sAPPPβ soluble
fragment produced by APP cleavage by β-secretase (BACE). Levels of BACE were significant
increase. Amounts of Aβ degrading enzymes neprilysin and endothelin-converting enzyme
decreased significantly after ischemia. We observed oxidative damage after ischemia.
Oxidative modifications of proteins were demonstrated by significant accumulation of
dityrosines and formation of lysine conjugates with the lipid peroxidation end products.
After ischemia levels of conjugated dienes increased significantly. Concentrations of free
sulfhydryl groups and thiobarbituric acid-reactive substances did not change during
ischemic insult. Our results suggest that global ischemia may lead to amyloid peptide
deposits accumulation and promote Alzheimer’s disease, which in turn might induce
protein and lipid oxidation and reactive oxygen species formation.
XXII. Biochemistry Congress, Martin
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