Effects of bradykinin potentiating peptide from B. jararaca snake on the way from the metabolism of L-arginine: interference in the mechanisms of dynamics control of the seminiferous epithelium

• Grant number: 13/09322-0
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2014
• End date: June 30, 2016
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Carlos Alberto da Silva
• Grantee: Carlos Alberto da Silva
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

The Bradykinin Potentiating Peptides (BPPs) were the first natural inhibitors of angiotensin-converting enzyme somatic (ACEs) described. Testicular isoform of ACE (ACEt) has been described and is distributed only in the germ cells during spermatogenesis in testis, as well as in sperm. Recently, our group has characterized the effects of BPP-10c and other BPPs on spermatogenesis of mice, taking into consideration: (i) the structural similarity between the C-terminal domain of ACEs and ACEt; (ii) the fact of BPP-10c and Captopril have inhibitory effects on the ACEs (Kiapp approximately 4.0 nM); (iii) the selectivity of the BPP-10c by the active site C-terminal of ACEs; (iv) the characteristics of the BTB prevent access of Captopril in testis. We have verified that the BPP-10c, a selective inhibitor of the site-C of ACEs, causes inhibition of spermatogenesis without affecting the permeability of the blood-testis barrier and distribution of Claudin-1, a protein of junction complexes of blood-testis barrier. Moreover, it has been shown in vitro the BPP-10c is able to modulate the catalytic activity of Arginosuccinate Synthase (AsS), increasing the availability of L-arginine. L-arginine is located on an intersection of divergent routes that can serve as a precursor for synthesis of polyamines as an alternative of the Citrulline-NO cycle. In this way, the affinity of the BPP-10 c by the AsS and its positive modulation would provide the increased levels of L-arginine and the elements of its route of metabolism (and polyamines) that could explain the gap junctional complexes, breaks in the seminiferous epithelium and the loss of germ cells into the lumen of the seminiferous tubules. With that, in the present study, investigating the metabolism of L-arginine as one of the mechanisms involved in impairment of spermatogenesis by the action of the BPP-10c other BPPs to be tested in this study. (AU)