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Title: Evidence of Lysosomal Membrane Permeabilization in Mucopolysaccharidosis Type I: Rupture of Calcium and Proton Homeostasis
Authors: Pereira, Vanessa Goncalves [UNIFESP]
Gazarini, Marcos L. [UNIFESP]
Rodrigues, Lara Cheliz [UNIFESP]
Da Silva, Flavia Helena [UNIFESP]
Han, Sang Won [UNIFESP]
Martins, Ana Maria [UNIFESP]
Tersariol, Ivarne L. S. [UNIFESP]
D'Almeida, Vania [UNIFESP]
Universidade Federal de São Paulo (UNIFESP)
Univ Fed Rio Grande do Sul
Issue Date: 1-May-2010
Publisher: Wiley-Blackwell
Citation: Journal of Cellular Physiology. Hoboken: Wiley-liss, v. 223, n. 2, p. 335-342, 2010.
Abstract: 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.
ISSN: 0021-9541
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