Evidence of Lysosomal Membrane Permeabilization in Mucopolysaccharidosis Type I: Rupture of Calcium and Proton Homeostasis

Evidence of Lysosomal Membrane Permeabilization in Mucopolysaccharidosis Type I: Rupture of Calcium and Proton Homeostasis

Autor Pereira, Vanessa Goncalves Autor UNIFESP Google Scholar
Gazarini, Marcos L. Autor UNIFESP Google Scholar
Rodrigues, Lara Cheliz Autor UNIFESP Google Scholar
Da Silva, Flavia Helena Autor UNIFESP Google Scholar
Han, Sang Won Autor UNIFESP Google Scholar
Martins, Ana Maria Autor UNIFESP Google Scholar
Tersariol, Ivarne L. S. Autor UNIFESP Google Scholar
D'Almeida, Vania Autor UNIFESP Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Univ Fed Rio Grande do Sul
Resumo Mucopolysaccharidosis type 1 (MPS1) is caused by a deficiency of alpha-iduronidase (IDUA), which leads to intralysosomal accumulation of glysosaminoglycans. Patients with MPS I present a wide range of clinical manifestations, but the mechanisms by which these alterations occur are still not fully understood. Genotype-phenotype correlations have not been well established for MPS1; hence, it is likely that secondary and tertiary alterations in cellular metabolism and signaling may contribute to the physiopathology of the disease. the aim of this study was to analyze Ca(2+) and H(+) homeostasis, lysosomal leakage of cysteine proteases, and apoptosis in a murine model of MPS1. After exposition to specific drugs, cells from Idua-/- mice were shown to release more Ca(2+) from the lysosomes and endoplasmic reticulum than Idua+/+ control mice, suggesting a higher intraorganelle store of this ion. A lower content of H(+) in the lysosomes and in the cytosol was found in cells from Idua-/- mice, suggesting an alteration of pH homeostasis. in addition, Idua-/- cells presented a higher activity of cysteine proteases in the cytosol and an increased rate of apoptotic cells when compared to the control group, indicating that lysosomal membrane permeabilization might occur in this model. Altogether, our results suggest that secondary alterations as changes in Ca(2+) and H(-) homeostasis and lysosomal membrane permeabilization may contribute for cellular damage and death in the physiopathology of MPS1. J. Cell. Physiol. 223: 335-342, 2010. (c) 2010 Wiley-Liss, Inc.
Idioma Inglês
Financiador Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
AFIP
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Número do financiamento CNPq: 501248/2005-6
CNPq: 500256/2008-0
CNPq: 301648/2007-7
CNPq: 306995/2006-9
Data de publicação 2010-05-01
Publicado em Journal of Cellular Physiology. Hoboken: Wiley-liss, v. 223, n. 2, p. 335-342, 2010.
ISSN 0021-9541 (Sherpa/Romeo, fator de impacto)
Publicador Wiley-Blackwell
Extensão 335-342
Fonte http://dx.doi.org/10.1002/jcp.22039
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000276428100007
Endereço permanente http://repositorio.unifesp.br/handle/11600/32498

Exibir registro completo




Arquivo

Arquivo Tamanho Formato Visualização

Não existem arquivos associados a este item.

Este item está nas seguintes coleções

Buscar


Navegar

Minha conta