Expression and localization of N-domain ANG I-converting enzymes in mesangial cells in culture from spontaneously hypertensive rats

Andrade, Maria Claudina; Marco, Giovana Seno Di; Teixeira, Vicente de Paulo Castro; Mortara, Renato Arruda; Sabatini, Regiane A.; Pesquero, João Bosco; Boim, Miriam Aparecida; Carmona, Adriana K.; Schor, Nestor; Casarini, Dulce Elena

doi:10.1152/ajprenal.00110.2005

Cited by 53 publications

(46 citation statements)

References 48 publications

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“…AT1R and AT2R have been demonstrated on the nuclear membranes in cardiomyocytes [11], hepatocytes, and vascular smooth muscle cell lines [78,79]. Ventricular myocytes express angiotensin and angiotensin converting enzyme (ACE) immunoreactivity is detected in nuclei of cultured rat cardiomyocytes and fibroblasts as well as mesangial cells cultured from spontaneously hypertensive rats [80,81]. Thus, Ang II can be generated intracellularly.…”

Section: Discussionmentioning

confidence: 99%

Intracrine endothelin signaling evokes IP3-dependent increases in nucleoplasmic Ca2+ in adult cardiac myocytes

Merlen¹,

Farhat²,

Luo³

et al. 2013

Journal of Molecular and Cellular Cardiology

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Endothelin receptors are present on the nuclear membranes in adult cardiac ventricular myocytes. The objectives of the present study were to determine 1) which endothelin receptor subtype is in cardiac nuclear membranes, 2) if the receptor and ligand traffic from the cell surface to the nucleus, and 3) the effect of increased intracellular ET-1 on nuclear Ca 2+ signalling. Confocal microscopy using fluorescently-labeled endothelin analogs confirmed the presence of ETB at the nuclear membrane of rat cardiomyocytes in skinned-cells and isolated nuclei. Furthermore, in both cardiac myocytes and aortic endothelial cells, endocytosed ET:ETB complexes translocated to lysosomes and not the nuclear envelope. Although ETA and ETB can form heterodimers, the presence or absence of ETA did not alter ETB trafficking. Treatment of isolated nuclei with * Abbreviations: The abbreviations used are: 2-APB, 2-aminoethoxydiphenyl borate; A, Angiotensin II; αAR, α-adrenergic receptor;[Ca 2+ ] n , nucleoplasmic free calcium concentration; CaMKII, Ca 2+ /calmodulin-dependent protein kinase II; DMNB, 4,5-dimethoxynitrobenzyl group; DNA, deoxyribonucleic acid; DCC, 1,3-dicyclohexylcarbodiimide; DCM, dichloromethane; DTT, dithiothreitol; ECE1-a, endothelin converting enzyme 1a; cET-1, caged ET-1; caged ET-1, [Trp-ODMNB 21 ]ET-1; ET-1, endothelin 1; ET-2, endothelin 2; ET-3, endothelin 3; ETA, endothelin type A receptor; ETB, endothelin type B receptor; ETR, endothelin receptor; GPCR, G protein-coupled receptor; HDAC5; histone deacetylase 5; IP3, inositol 1,4,5-trisphosphate; IP3R, inositol 1,4,5-trisphosphate receptor; ISO, isoproterenol; MEF2, myocyte enhancing factor-2; PBS, phosphate buffered saline; PMSF, phenylmethanesulphonylfluoride; PNGase F, peptide N-glycosidase F; qPCR, quantitative real-time polymerase chain reaction; RNA, ribonucleic acid; RyR, ryanodine receptor; TCA, trichloroacetic acid; TFA, trifluoroacetic acid; TX-100, Triton X-100. Address correspondence to: Bruce G. Allen, Montreal Heart Institute, 5000 Belanger St,. Montréal, Québec, Canada, H1T 1C8., Telephone: (514) ] n whereas extracellular application of ETA and ETB receptor antagonists did not. These data suggest that 1) the endothelin receptor in the cardiac nuclear membranes is ETB, 2) ETB traffic directly to the nuclear membrane after biosynthesis, 3) exogenous endothelins are not ligands for ETB on nuclear membranes, and 4) ETB associated with the nuclear membranes regulate nuclear Ca 2+ signalling.

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Section: Discussionmentioning

confidence: 99%

Intracrine endothelin signaling evokes IP3-dependent increases in nucleoplasmic Ca2+ in adult cardiac myocytes

Merlen¹,

Farhat²,

Luo³

et al. 2013

Journal of Molecular and Cellular Cardiology

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“…Além das células mesangiais, todos os componentes do SRA foram detectados em células epiteliais do túbulo proximal (31), células endoteliais glomerulares (32) e células do ducto coletor (33). Em especial, sabe-se que a ECA N-domínio encontra-se localizada no núcleo das células mesangiais em cultura primária e é responsável pela transcrição de novos genes (34).…”

Section: Eventos Moleculares Da Lesão Glomerular Associados à Elevaçãunclassified

Bases moleculares da glomerulopatia diabética

Lagranha¹,

Fiorino²,

Casarini

et al. 2007

Arq Bras Endocrinol Metab

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RESUMOO principal determinante da nefropatia diabética é a hiperglicemia, mas hipertensão e fatores genéticos também estão envolvidos. O glomérulo é o foco de lesão, onde proliferação celular mesangial e produção excessiva de matriz extracelular decorrem do aumento da glicose intracelular, por excesso de glicose extracelular e hiperexpressão de GLUT1. Seguem-se aumento do fluxo pela via dos polióis, estresse oxidativo intracelular, produção intracelular aumentada de produtos avançados da glicação não enzimática (AGEs), ativação da via da PKC, aumento da atividade da via das hexosaminas e ativação de TGF-β1. Altas concentrações de glicose também aumentam angiotensina II (AII) nas células mesangiais por aumento intracelular da atividade da renina (ações intrácrinas, mediando efeitos proliferativos e inflamatórios diretamente). Portanto, glicose e AII exercem efeitos proliferativos celulares e de matriz extracelular nas células mesangiais, utilizando vias de transdução de sinais semelhantes, que levam a aumento de TGF-β1. Nesse estudo são revisadas as vias que sinalizam os efeitos da glicose e AII nas células mesangiais em causar os eventos-chaves relacionados à gênese da glomerulopatia diabética. As alterações das vias de sinalização implicadas na glomerulopatia, aqui revisadas, suportam dados de estudos observacionais/ensaios clínicos, onde controle metabólico e anti-hipertensivo, especificamente com inibidores do sistema renina-angiotensina, têm-se mostrado importantes -e aditivos -na prevenção do início e progressão da nefropatia. Novas estratégias terapêuticas dirigidas aos eventos intracelulares descritos deverão futuramente promover benefício adicional. ABSTRACT Molecular Bases of Diabetic Nephropathy.The determinant of the diabetic nephropathy is hyperglycemia, but hypertension and other genetic factors are also involved. Glomerulus is the focus of the injury, where mesangial cell proliferation and extracellular matrix occur because of the increase of the intra-and extracellular glucose concentration and overexpression of GLUT1. Sequentially, there are increases in the flow by the poliol pathway, oxidative stress, increased intracellular production of advanced glycation end products (AGEs), activation of the PKC pathway, increase of the activity of the hexosamine pathway, and activation of TGF-β1. High glucose concentrations also increase angiotensin II (AII) levels. Therefore, glucose and AII exert similar effects in inducing extracellular matrix formation in the mesangial cells, using similar transductional signal, which increases TGF-β1 levels. In this review we focus in the effect of glucose and AII in the mesangial cells in causing the events related to the genesis of diabetic nephropathy. The alterations in the signal pathways discussed in this review give support to the observational studies and clinical assays, where metabolic and antihypertensive controls obtained with angiotensin-converting inhibitors have shown important and additive effect in the prevention of the beginning and progression of d...

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“…[11][12][13][14][15][16] In addition to the RAAS, the kallikrein/kinin system (KKS) represents an important regulator of cardiocirculatory function. Kinins are potent vasodilator peptides formed by the action of 17 The role of the KKS and RAAS in cardiocirculatory control can be better understood if we analyze the interaction between Ang(1-7) and BK in many tissues and animal models.…”

Section: Introductionmentioning

confidence: 99%

Renin-angiotensin system may trigger kidney damage in NOD mice

Colucci

Arita

Cunha

et al. 2010

J Renin Angiotensin Aldosterone Syst

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Diabetic nephropathy is a complication of diabetes and one of the main causes of end-stage renal disease. A possible causal link between renin-angiotensin aldosterone system (RAAS) and diabetes is widely recognized but the mechanisms by which the RAAS may lead to this complication remains unclear. The aim of this study was to evaluate angiotensin-I converting enzyme (ACE) activity and expression in numerous tissues, especially kidney, of non-obese diabetic mouse. Kidney, lung, pancreas, heart, liver and adrenal tissues from diabetic and control female NOD mice were homogenized for measurement of ACE activity, SDS-PAGE and Western blotting for ACE and ACE2, immunohistochemistry for ACE and angiotensins I, II and 1-7 and bradykinin quantification. ACE activity was higher in kidney, lung and adrenal tissue of diabetic mice compared with control mice. In pancreas, activity was decreased in the diabetic group. Western blotting analysis indicated that both groups presented ACE isoforms with molecular weights of 142 and 69 kDa and a decrease in ACE2 protein expression. Angiotensin concentrations were not altered within groups, although bradykinin levels were higher in diabetic mice. The immunohistochemical study in kidney showed an increase in tubular ACE expression. Our results show that the RAAS is affected by diabetes and the elevated ACE/ACE2 ratio may contribute to renal damage.

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Expression and localization of N-domain ANG I-converting enzymes in mesangial cells in culture from spontaneously hypertensive rats

Cited by 53 publications

References 48 publications

Intracrine endothelin signaling evokes IP3-dependent increases in nucleoplasmic Ca2+ in adult cardiac myocytes

Intracrine endothelin signaling evokes IP3-dependent increases in nucleoplasmic Ca2+ in adult cardiac myocytes

Bases moleculares da glomerulopatia diabética

Renin-angiotensin system may trigger kidney damage in NOD mice

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