Role of caspase-3 in regulation of the amyloid-degrading neuropeptidase neprilysin level in the rat cortex after hypoxia

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% О 2 , 3 h) on day 14 of embryonic development (E14) was performed. It was found that rats exposed to prenatal hypoxia on days 20–30...

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Published in:Journal of evolutionary biochemistry and physiology 2015-11, Vol.51 (6), p.480-484
Main Authors: Kozlova, D. I., Vasylev, D. S., Dubrovskaya, N. M., Nalivaeva, N. N., Tumanova, N. L., Zhuravin, I. А.
Format: Article
Language:English
Subjects:
Animal Physiology
Biochemistry
Biomedical and Life Sciences
Brain
Comparative and Ontogenic Biochemistry
Enzymes
Evolutionary Biology
Hypoxia
Life Sciences
Neuropeptides
Rodents
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Summary: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% О 2 , 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.
ISSN:0022-0930
1608-3202
DOI:10.1134/S0022093015060046