Evaluation of the effect of hypoxia on the expression and activity of neprilysin (EC 3.4.24.11), a protease involved in Alzheimer's Disease

• Grant number: 11/16011-6
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): March 01, 2012
• Effective date (End): February 28, 2014
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Jair Ribeiro Chagas
• Grantee: Renato Watanabe de Oliveira
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Hypoxia is characterized by reduced oxygen content in blood and is related to several pathologies, including Obstructive Sleep Apnea Syndrome (OSAS). Its consequences are not completely understood, but some evidences from the literature show that hypoxia has biochemical effects that lead to changes on behavior and significant outcomes in systems like the central nervous, respiratory and cardiovascular systems. Hypoxia and age seem to have a very close involvement in the development of Alzheimer's disease. Neprilysin or neutralpeptidase (NEP, EC 3.4.24.11) is a metalloprotease present in various body tissues such as kidneys, intestines, lungs, brain, among others. It was recently shown that one of its main activities in the central nervous system is the degradation of beta amyloid (A²), a peptide involved in the onset and progression of Alzheimer's disease. Our goal is to study the expression and activity of NEP in male rats using a model of intermittent hypoxia (IH) model that mimics the hypoxia observed during OSAS. Wistar rats will be submitted to intermittent hypoxia (IH 3-min cycles of 21% to 5% O2) from 9 to 17h for six weeks. The expression of NEP will be evaluated by qRT-PCR, enzyme activity, immunohistochemistry and immunoblotting and compared to a control group, submitted to the same conditions but without hypoxia. (AU)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

JULIAN, GUILHERME SILVA; DE OLIVEIRA, RENATO WATANABE; FAVARO, VANESSA MANCHIM; MENEZES DE OLIVEIRA, MARIA GABRIELA; PERRY, JULIANA CINI; TUFIK, SERGIO; CHAGAS, JAIR RIBEIRO. Chronic intermittent hypoxia increases encoding pigment epithelium-derived factor gene expression, although not that of the protein itself, in the temporal cortex of rats. Jornal Brasileiro de Pneumologia, v. 41, n. 1, p. 39-47, JAN-FEB 2015. (11/16011-6, 11/03791-3)

DE OLIVEIRA, RENATO W.; JULIAN, GUILHERME S.; PERRY, JULIANA C.; TUFIK, SERGIO; CHAGAS, JAIR R.. Chronic intermittent hypoxia induces changes on the expression and activity of neprilysin (EC 3.4.24.11) in the brain of rats. Neuroscience Letters, v. 678, p. 43-47, JUN 21 2018. (11/16011-6)

GUILHERME SILVA JULIAN; RENATO WATANABE DE OLIVEIRA; SERGIO TUFIK; JAIR RIBEIRO CHAGAS. Análise da estabilidade da expressão de genes de referência no ventrículo cardíaco esquerdo de ratos submetidos à hipóxia intermitente crônica. Jornal Brasileiro de Pneumologia, v. 42, n. 3, p. 211-214, 2016-06-00. (11/16011-6)

JULIAN, GUILHERME SILVA; DE OLIVEIRA, RENATO WATANABE; PERRY, JULIANA CINI; TUFIK, SERGIO; CHAGAS, JAIR RIBEIRO. Validation of Housekeeping Genes in the Brains of Rats Submitted to Chronic Intermittent Hypoxia, a Sleep Apnea Model. PLoS One, v. 9, n. 10, OCT 7 2014. (11/16011-6)