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Molecular mechanism of intracellular peptides on gene expression and signaling in skeletal muscle model

Grant number: 15/07273-8
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Start date: December 01, 2015
End date: November 30, 2017
Field of knowledge:Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
Principal Investigator:Emer Suavinho Ferro
Grantee:Ricardo Pariona Llanos
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The oligopeptidase neurolysin (EC 3.4.24.16; Nln) was first identified in synaptic membranes of the rat brain, participating ubiquitously in the catabolism of bioactive peptides such as neurotensin and bradykinin. Recently, it was shown that knockout mice for Nln (KO) present an increase in glucose uptake, insulin sensitivity and gluconeogenesis. The liver of KO animals have increased mRNA for several genes involved in gluconeogenesis, whereas in the gastrocnemius muscle KO animals have reduced expression of several genes. The semi-quantitative peptidomic analysis after isotope labeling of the isolated peptides suggests an increase in specific intracellular peptides from gastrocnemius muscle and epididymal adipose tissue, whereas in liver and soleus muscle a predominant reduction of these peptides was observed. Considering the restricted biological activity of oligopeptidases such as Nln a possibility is that intracellular peptides are actively participating in the regulation of gene expression, which therefore define the altered phenotypes of these KO animals. Thus, an exciting possibility exist that intracellular peptides substracts/products of Nln are essential for energy metabolism, and can be used to enhance glucose uptake and insulin sensitivity. Therefore, the main aim of this project is to investigate the molecular mechanism of action of specific intracellular peptides on gene expression and signaling in a model of skeletal muscle cell culture.

News published in Agência FAPESP Newsletter about the scholarship:
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Scientific publications
(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)
SILVA, RENEE N. O.; LLANOS, RICARDO P.; EICHLER, ROSANGELA A. S.; OLIVEIRA, THIAGO B.; GOZZO, FABIO C.; FESTUCCIA, WILLIAM T.; FERRO, EMER S.. New Intracellular Peptide Derived from Hemoglobin Alpha Chain Induces Glucose Uptake and Reduces Blood Glycemia. PHARMACEUTICS, v. 13, n. 12, . (15/07273-8, 16/04000-3)
DOS SANTOS, NILTON B.; FRANCO, ROSEANE D.; CAMARINI, ROSANA; MUNHOZ, CAROLINA D.; EICHLER, ROSANGELA A. S.; GEWEHR, MAYARA C. F.; RECKZIEGEL, PATRICIA; LLANOS, RICARDO P.; DALE, CAMILA S.; DA SILVA, VICTORIA R. O.; et al. Thimet Oligopeptidase (EC 3.4.24.15) Key Functions Suggested by Knockout Mice Phenotype Characterization. BIOMOLECULES, v. 9, n. 8, . (16/04000-3, 15/07273-8, 04/04933-2, 15/20657-0)

Filed patent(s) as a result of this research project

PEPTÍDEO, COMPOSIÇÃO FARMACÊUTICA COMPREENDENDO O MESMO E USO BR1020180105230 - Universidade Estadual de Campinas (UNICAMP) . Fabio Cesar Gozzo / EMER SUAVINHO / RICARDO PARIONA LLANOS - May 2018, 23