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Effect of Hypoxia/Ischemia and Hypoxic Preconditioning/Reperfusion on Expression of Some Amyloid‐Degrading Enzymes
Author(s) -
NALIVAEVAA NATALIA N.,
FISK LILIA,
KOCHKINA EKATERINA G.,
PLESNEVA SVETLANA A.,
ZHURAVIN IGOR A.,
BABUSIKOVA EVA,
DOBROTA DUSAN,
TURNER ANTHONY J.
Publication year - 2004
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1332.002
Subject(s) - neprilysin , amyloid precursor protein , neuroprotection , amyloid precursor protein secretase , proteases , hypoxia (environmental) , ischemia , proteolysis , chemistry , brain ischemia , p3 peptide , biochemistry , pharmacology , endocrinology , microbiology and biotechnology , medicine , biology , enzyme , alzheimer's disease , disease , oxygen , organic chemistry
A bstract : Alzheimer's disease (AD) is linked to certain common brain pathologies (e.g., ischemia, stroke, and trauma) believed to facilitate its development and progression. One of the logical approaches to this problem is to study the effects of ischemia and hypoxia on the metabolism of amyloid precursor protein, which plays one of the key roles in the pathogenesis of AD. This involves an analysis of (1) proteases, which participate in proteolysis of amyloid precursor protein either by the nonamyloidogenic route (α‐secretase) or the amyloidogenic pathway and lead to formation of toxic β‐amyloid peptides (β‐ and γ‐secretases) and (2) several metallopeptidases that might play a role in degradation of β‐amyloid peptide (Aβ). The study of the effects of prenatal hypoxia and acute hypoxia in adult animals allowed us to conclude that oxygen deprivation results not only in an increase of amyloid precursor protein expression in the brain but also in a decrease in the activity of α‐secretase. In some brain structures involved in AD pathology (the cortex and striatum), we also observed a decrease in the expression of two of the Aβ degrading enzymes, neprilysin and endothelin‐converting enzyme, after hypoxia. A decrease in expression of these metalloproteases was also observed in the model of four‐vessel occlusion ischemia in rats with their restoration to the control levels after reperfusion. Preconditioning to mild hypoxia both in the prenatal period and in adults appeared to have a neuroprotective effect restoring, in particular, the levels of amyloid precursor protein, activity of a‐secretase, and expression of neprilysin and endothelin‐converting enzyme to their control values.