Alterations on cellular homeostasis of mucopolysaccharidosis type I mice

• Grant number: 11/18050-9
• Support Opportunities: Regular Research Grants
• Start date: January 01, 2012
• End date: December 31, 2013
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Vânia D'Almeida
• Grantee: Vânia D'Almeida
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Mucopolysaccharidosis type I (MPS I) is a hereditary disease caused by the deficiency of alpha-L-iduronidase (IDUA), leading to an impaired glycosaminoglycan (GAG) degradation. When not degraded, GAG accumulates in various tissues and organs, leading to a chronic, progressive and multisystem disease. The cellular mechanisms responsible for the disease etiology, however, are still not fully understood. In a recent paper published by our group (Pereira et al., 2010), alterations in intracellular ion homeostasis and lysosomal permeability were described in Idua -/- mice splenocytes, suggesting the involvement of secondary metabolic and signaling pathways in physiopathology of this disease. The aim of this study is to investigate the relation between ionic homeostasis (intracellular Ca2+ and H+ mobilization), lysosomal permeability (release of cathepsin D into cytosol), autophagy (LC3-I/LC3-II ratio and beclin-1 levels) and apoptosis (caspases activities and pro/anti-apoptotic markers) in primary fibroblasts and hepatocytes cultures from Idua -/- and +/+ mice. The evaluation of alterations on cellular metabolism of this animal model of MPS I bring new perspectives for further studies on patients' cells, as allows a better understanding about the physiopathology of the disease. (AU)

Scientific publications

(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)

VIANA, GUSTAVO MONTEIRO; BURI, MARCUS VINICIUS; PAREDES-GAMERO, EDGAR JULIAN; MARTINS, ANA MARIA; D'ALMEIDA, VANIA. Impaired Hematopoiesis and Disrupted Monocyte/Macrophage Homeostasis in Mucopolysaccharidosis Type I Mice. Journal of Cellular Physiology, v. 231, n. 3, p. 698-707, MAR 2016. (11/18050-9, 10/10458-6)