Altered Cellular Homeostasis in Murine MPS I Fibroblasts: Evidence of Cell-Specific Physiopathology

  • Gustavo Monteiro VianaEmail author
  • Cinthia Castro do Nascimento
  • Edgar Julian Paredes-Gamero
  • Vânia D’Almeida
Research Report
Part of the JIMD Reports book series (JIMD, volume 36)


Mucopolysaccharidosis type I (MPS I), a rare autosomal recessive disease, is caused by a deficiency of the lysosomal enzyme alfa-l-iduronidase. Impaired enzyme activity promotes glycosaminoglycans accumulation in several tissues and organs, leading to complex multisystemic complications. Several studies using animal models indicated different intracellular pathways involving MPS I physiopathology; however, the exact mechanisms underlying this syndrome are still not understood. Previous results from our group showed alterations in ionic homeostasis and cell viability of splenocytes and macrophages in Idua−/− mice. In the present study, we found altered intracellular ionic homeostasis in a different cell type (fibroblasts) from the same murine model. Idua−/− fibroblasts from 3-month-old mice presented higher cytoplasmatic and endoplasmic reticulum Ca2+ concentration, lower levels of mitochondrial Ca2+ and mitochondrial membrane potential and higher cytoplasmatic pH when compared to Idua+/+ animals. Also, Idua−/− fibroblasts were more resistant to the apoptotic induction with staurosporine, indicating a possible resistance to apoptotic induction in those cells. In addition, despite the intracellular ionic imbalance, no significant alterations were found in apoptosis and autophagy in Idua−/− fibroblasts, which implies that the ionic alterations did not activate those pathways. The investigation of mechanisms underlying the cellular physiopathology of lysosomal diseases is crucial for a better understanding about the progression of these diseases. Since splenocytes, macrophages, and fibroblasts have different embryonic origins and distinct structural and functional features, potentially altered signaling pathways found in a cell-specific manner in an alfa-l-iduronidase-deficient environment provide additional understanding of the clinical multisystemic presentation of this disease and provide new basis for improved therapeutic approaches.


Apoptosis Autophagy Calcium Fibroblasts Mucopolysaccharidosis type I 



This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) research grant # 2011/18050-9 (Vânia D’Almeida). The authors would also like to thank CAPES, CNPq, and AFIP for additional financial and infrastructural support, Dr. Helena Nader for providing access to the microscopy facility at INFAR, UNIFESP, and Dr. Marcelo Lima for his critical reading of this manuscript. Vânia D’Almeida was recipient of a fellowship from CNPq. Gustavo Viana was a recipient of a FAPESP Ph.D. scholarship (# 2010/10458-6).


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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Gustavo Monteiro Viana
    • 1
    • 2
    Email author
  • Cinthia Castro do Nascimento
    • 3
  • Edgar Julian Paredes-Gamero
    • 4
  • Vânia D’Almeida
    • 3
  1. 1.Department of PediatricsUniversidade Federal de São PauloSão PauloBrazil
  2. 2.Department of BiochemistryUniversidade Federal de São PauloSão PauloBrazil
  3. 3.Department of PsychobiologyUniversidade Federal de São PauloSão PauloBrazil
  4. 4.Centro Interdisciplinar de Investigação BioquímicaUniversidade de Mogi das CruzesMogi das CruzesBrazil

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