Soluble uric acid increases intracellular calcium through an angiotensin II-dependent mechanism in immortalized human mesangial cells

Soluble uric acid increases intracellular calcium through an angiotensin II-dependent mechanism in immortalized human mesangial cells

Author Albertoni, Guilherme Autor UNIFESP Google Scholar
Maquigussa, Edgar Autor UNIFESP Google Scholar
Pessoa, Edson Autor UNIFESP Google Scholar
Barreto, Jose Augusto Google Scholar
Borges, Fernanda Autor UNIFESP Google Scholar
Schor, Nestor Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Assoc Beneficente Coleta Sangue Colsan
Abstract Hyperuricemia is associated with increases in cardiovascular risk and renal disease. Mesangial cells regulate glomerular filtration rates through the release of hormones and vasoactive substances. This study evaluates the signaling pathway of uric acid (UA) in immortalized human mesangial cells (ihMCs). To evaluate cell proliferation, ihMCs were exposed to UA (6-10 mg/dL) for 24-144 h. in further experiments, ihMCs were treated with UA (6-10 mg/dL) for 12 and 24 h simultaneously with losartan (10(-7) mmol/L). Angiotensin II (All) and endothelin-1 (ET-1) were assessed using the enzyme-linked immunosorbent assay (ELISA) technique. Pre-pro-ET mRNA was evaluated by the real-time PCR technique. It was observed that soluble UA (8 and 10 mg/dL) stimulated cellular proliferation. UA (10 mg/dL) for 12 h significantly increased All protein synthesis and ET-1 expression and protein production was increased after 24 h. Furthermore, UA increased [Ca(2+)](i), and this effect was significantly blocked when ihMCs were preincubated with losartan. Our results suggested that UA triggers reactions including All and ET-1 production in mesangial cells. in addition, UA can potentially affect glomerular function due to UA-induced proliferation and contraction of mesangial cells. the latter mechanism could be related to the long-term effects of UA on renal function and chronic kidney disease.
Keywords uric acid
angiotensin II
intracellular calcium
mesangial cells
Language English
Sponsor Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Financiadora de Estudos e Projetos (FINEP)
Fundacao Oswaldo Ramos (FOR)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Associacao Beneficente de Coleta de Sangue (COLSAN)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Date 2010-07-01
Published in Experimental Biology and Medicine. Maywood: Soc Experimental Biology Medicine, v. 235, n. 7, p. 825-832, 2010.
ISSN 1535-3702 (Sherpa/Romeo, impact factor)
Publisher Soc Experimental Biology Medicine
Extent 825-832
Access rights Closed access
Type Article
Web of Science ID WOS:000279628800005

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