Angiotensin I: converting enzyme isoform (90 kDa), potential genetic marker of hypertension: processing, molecular and functional characterization, and genetic segregation

• Grant number: 02/13290-2
• Support Opportunities: Research Projects - Thematic Grants
• Start date: November 01, 2004
• End date: February 28, 2009
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Dulce Elena Casarini
• Grantee: Dulce Elena Casarini
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Pesquisadores principais: Mirian Aparecida Boim ; Ricardo de Castro Cintra Sesso ; Sergio Atala Dib

Abstract

N-domain mRNA species has not been described in the literature. Thus, our objective will be evaluated the molecular and functional characterization and processing of ACE isoforms through a identification of mRNA of N-domain ACE, trying to understand their mechanisms of formation, transport and the cell fractionation, specially the 90kDa enzyme. Also, in another study, these isoforms will be mapped in the tissues of mice, comparing them with the ones obtained in rats, we have attempted to verify the presence or absence of the N-domain isoform. In the structural characterization, sequence of these 90 and 65kDa ACE N-domain isoforms of human urine and mesangial cells in culture, they will be more completely known. It can be pointed out that a more thorough study of the structure from this marker reaching crystallization can contribute for the development of new medicaments that can be involved in blood pressure control. In this new project, we will be initially carrying out the final standardization of the methods for quantification of ACE isoform by mass spectrometry and western blotting, with the purpose of obtaining a predicting test for hypertension. Segregation of ACE isoforms will be done through a study of the genetic transmission from ACE isoforms (190kDa, 90/80 kDa and 65kDa), a possible genetic marker for hypertension, in the crossing and retrocrossing of SHR versus Brown Norway; in an 80-member family; in the functional study, it is our intention to use this marker to discover if its transference occurs after a renal transplant, for it is known that the cells present in the graft migrate to the receptor, just as the cells (passenger leukocytes) from the receptor start to get installed in the graft (microquimerism), which can raise the question of what its relationship with hypertension is; and finally the incidence of these isoforms will be evaluated in a determined population. The last years (November of 2002/ February of 2004) despite our lack of grants, we have succeed in the realization of some topics that we proposed in the presentation of this project on November of 2002. We described that the isoforms of 90/80 kDa and 65 kDa are expressed in all studied tissues and they are not restricted to the kidney (submitted to the Journal of Hypertension, see attachment). We demonstrated that the enzyme with 80/90 kDa is higher expressed in the model 2K1C using SHR animals (submitted, see attachment)... (AU)

Scientific publications

(11)

(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)

COLUCCI, JULIANA ALMADA; ARITA, DANIELLE YURI; CUNHA, TATIANA SOUSA; DI MARCO, GIOVANA SENO; VIO, CARLOS P.; PACHECO-SILVA, ALVARO; CASARINI, DULCE ELENA. Renin-angiotensin system may trigger kidney damage in NOD mice. JOURNAL OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM, v. 12, n. 1, p. 15-22, MAR 2011. (02/13290-2)

MEI WANG, PAMELLA HUEY; ANDRADE, MARIA CLAUDINA; REDUBLO QUINTO, BEATA MARIE; DI MARCO, GIOVANA; MORTARA, RENATO ARRUDA; VIO, CARLOS P.; CASARINI, DULCE ELENA. N-domain angiotensin-I converting enzyme is expressed in immortalized mesangial, proximal tubule and collecting duct cells. International Journal of Biological Macromolecules, v. 72, p. 380-390, JAN 2015. (02/13290-2)

DE ANDRADE, MARIA C. C.; AFFONSO, REGINA; FERNANDES, FERNANDA B.; FEBBA, ANDREIA C.; DA SILVA, ISMAEL D. C. G.; STELLA, REGINA C. R.; MARSON, ODAIR; JUBILUT, GUITA N.; HIRATA, IZAURA Y.; CARMONA, ADRIANA K.; et al. Spectroscopic and structural analysis of somatic and N-domain angiotensin I-converting enzyme isoforms from mesangial cells from Wistar and spontaneously hypertensive rats. International Journal of Biological Macromolecules, v. 47, n. 2, p. 238-243, AUG 1 2010. (02/13290-2)

DI MARCO, GIOVANA SENO; COLUCCI, JULIANA ALMADA; FERNANDES, FERNANDA BARRINHA; VIO, CARLOS PABLO; SCHOR, NESTOR; CASARINI, DULCE ELENA. Diabetes induces changes of catecholamines in primary mesangial cells. INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, v. 40, n. 4, p. 747-754, 2008. (02/13290-2)

MALUF-MEIKEN, LEILA C. V.; FERNANDES, FERNANDA B.; ARAGAO, DANIELLE S.; RONCHI, FERNANDA A.; ANDRADE, MARIA C. C.; FRANCO, MARIA C.; FEBBA, ANDREIA C. S.; PLAVNIK, FRIDA L.; KRIEGER, JOSE E.; MILL, JOSE G.; et al. N-Domain Isoform of Angiotensin I Converting Enzyme as a Marker of Hypertension: Populational Study. INTERNATIONAL JOURNAL OF HYPERTENSION, v. 2012, p. 9-pg., 2012-01-01. (02/13290-2, 10/51904-9)

ARITA, DANIELLE YURI; CUNHA, TATIANA SOUSA; PEREZ, JULIANA DINEIA; COLUCCI, JULIANA ALMADA; RONCHI, FERNANDA APARECIDA; NOGUEIRA, MARIE DOKI; ARITA, LILIAN SAEMI; ARAGAO, DANIELLE SANCHES; CASTRO TEIXEIRA, VICENTE DE PAULO; CASARINI, DULCE ELENA. Overexpression of Urinary N-Domain ACE in Chronic Kidney Dysfunction in Wistar Rats. CLINICAL AND EXPERIMENTAL HYPERTENSION, v. 34, n. 6, p. 389-396, 2012. (02/13290-2)

CLEBER A LEITE; NÁDIA SC BERTONCELLO; INGRID KM WATANABE; FERNANDA B FERNANDES; MARIA CLAUDINA C ANDRADE; FERNANDA A RONCHI; DANIELLE Y ARITA; FERNANDA K MARCONDES; TATIANA S CUNHA; DULCE E CASARINI. Enzima conversora de angiotensina I (ECA) N-domínio 90-kDa: possível marcador para hipertensão em modelo de transplante renal. J. Bras. Nefrol., v. 39, n. 1, p. 11-14, 2017-03-00. (02/13290-2)

ANDRADE, MARIA CLAUDINA CAMARGO DE; DI MARCO, GIOVANA SENO; TEIXEIRA, VICENTE DE PAULO CASTRO; MORTARA, RENATO ARRUDA; SABATINI, REGIANE ANGÉLICA; PESQUERO, JOÃO BOSCO; BOIM, MIRIAM APARECIDA; CARMONA, ADRIANA KARAOGLANOVIC; SCHOR, NESTOR; CASARINI, DULCE ELENA. Expression and localization of N-domain ANG I-converting enzymes in mesangial cells in culture from spontaneously hypertensive rats. American Journal of Physiology : Renal Physiology, v. 290, n. 2, p. F364-F375, Feb. 2006. (02/13290-2)

QUINTO, BEATA MARIE REDUBLO; ANDRADE, MARIA CLAUDINA CAMARGO DE; RONCHI, FERNANDA APARECIDA; SANTOS, EDSON LUCAS; CORREA, SILVANA APARECIDA ALVES; SHIMUTA, SUMA IMURA; PESQUERO, JOÃO BOSCO; MORTARA, RENATO ARRUDA; CASARINI, DULCE ELENA. Expression of angiotensin I-converting enzymes and bradykinin B-2 receptors in mouse inner medullary-collecting duct cells. International Immunopharmacology, v. 8, n. 2, p. 254-260, Feb. 2008. (02/13290-2)

A.M.S. TEIXEIRA; F.L. PLAVNIK; F.B. FERNANDES; O. MARSON; D.M.J. CHRISTOFALO; S.A. AJZEN; R. SESSO; M.C. FRANCO; D.E. CASARINI. Association of urinary 90 kDa angiotensin- converting enzyme with family history of hypertension and endothelial function in normotensive individuals. Brazilian Journal of Medical and Biological Research, v. 41, n. 5, p. 351-356, 2008-04-30. (02/13290-2)

FERNANDES‚ F.B.; PLAVNIK‚ F.L.; TEIXEIRA‚ A.M.S.; CHRISTOFALO‚ D.M.J.; AJZEN‚ S.A.; HIGA‚ E.M.S.; RONCHI‚ F.A.; SESSO‚ R.C.C.; CASARINI‚ D.E.. Association of urinary N-domain Angiotensin I-converting enzyme with plasma inflammatory markers and endothelial function. Molecular Medicine, v. 14, n. 7-8, p. 429, 2008. (02/13290-2)

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