Abstract
Analysis of the effect of a caspase-3 inhibitor on the level of amyloid-degrading neuropeptidase neprilysin (NEP) in the cortex of rats exposed to prenatal hypoxia (7% О2, 3 h) on day 14 of embryonic development (E14) was performed. It was found that rats exposed to prenatal hypoxia on days 20–30 after birth had an increased level and activity of caspase-3 with reduced levels of NEP and the C-terminal fragment of the amyloid precursor protein intracellular domain (AICD) which regulates NEP expression. In hypoxic animals 3 days after a single intraventricular injection of a caspase inhibitor (Ac-DEVD-CHO) on P20, the AICD and NEP levels were found to be increased up to the levels observed in control rats. The results suggest that the increase in caspase-3 enzyme activity could affect NEP expression via proteolytic degradation of its transcription factor AICD. These findings represent the first demonstration of the role of caspases in AICD-dependent regulation of NEP production in the brain of mammals under hypoxic conditions.
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Original Russian Text © D.I. Kozlova, D.S. Vasylev, N.М. Dubrovskaya, N.N. Nalivaeva, N.L. Tumanova, I.А. Zhuravin, 2015, published in Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, 2015, Vol. 51, No. 6, pp. 427—430.
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Kozlova, D.I., Vasylev, D.S., Dubrovskaya, N.M. et al. Role of caspase-3 in regulation of the amyloid-degrading neuropeptidase neprilysin level in the rat cortex after hypoxia. J Evol Biochem Phys 51, 480–484 (2015). https://doi.org/10.1134/S0022093015060046
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DOI: https://doi.org/10.1134/S0022093015060046