Effect of Global Brain Ischemia on Amyloid Precursor Protein Metabolism and Expression of Amyloid-Degrading Enzymes in Rat Cortex: Role in Pathogenesis of Alzheimer’s Disease

Autor:	Eva Babusikova, Natalia N. Nalivaeva, Anthony J. Turner, Dusan Dobrota
Rok vydání:	2021
Předmět:	Male medicine.medical_specialty Amyloid Ischemia Brain damage Endothelin-Converting Enzymes medicine.disease_cause Insulysin Biochemistry Brain Ischemia Brain ischemia Lipid peroxidation Amyloid beta-Protein Precursor chemistry.chemical_compound Alzheimer Disease Internal medicine medicine Amyloid precursor protein Animals Rats Wistar Neprilysin Cerebral Cortex biology Chemistry General Medicine medicine.disease Rats Oxidative Stress Endocrinology Gene Expression Regulation Reperfusion Injury biology.protein Amyloid Precursor Protein Secretases medicine.symptom Oxidative stress
Zdroj:	Biochemistry (Moscow). 86:680-692
ISSN:	1608-3040 0006-2979
DOI:	10.1134/s0006297921060067
Popis:	The incidence of Alzheimer's disease (AD) increases significantly following chronic stress and brain ischemia which, over the years, cause accumulation of toxic amyloid species and brain damage. The effects of global 15-min ischemia and 120-min reperfusion on the levels of expression of the amyloid precursor protein (APP) and its processing were investigated in the brain cortex (Cx) of male Wistar rats. Additionally, the levels of expression of the amyloid-degrading enzymes neprilysin (NEP), endothelin-converting enzyme-1 (ECE-1), and insulin-degrading enzyme (IDE), as well as of some markers of oxidative damage were assessed. It was shown that the APP mRNA and protein levels in the rat Cx were significantly increased after the ischemic insult. Protein levels of the soluble APP fragments, especially of sAPPβ produced by β-secretase, (BACE-1) and the levels of BACE-1 mRNA and protein expression itself were also increased after ischemia. The protein levels of APP and BACE-1 in the Cx returned to the control values after 120-min reperfusion. The levels of NEP and ECE-1 mRNA also decreased after ischemia, which correlated with the decreased protein levels of these enzymes. However, we have not observed any changes in the protein levels of insulin-degrading enzyme. Contents of the markers of oxidative damage (di-tyrosine and lysine conjugates with lipid peroxidation products) were also increased after ischemia. The obtained data suggest that ischemia shifts APP processing towards the amyloidogenic β-secretase pathway and accumulation of the neurotoxic Aβ peptide as well as triggers oxidative stress in the cells. These results are discussed in the context of the role of stress and ischemia in initiation and progression of AD.
Databáze:	OpenAIRE
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