Low-Concentration Methylene Blue Maintains Energy Production and Strongly Improves Survival of Leigh Syndrome French Canadian Skin Fibroblasts

Authors

  • Jean Legault Université du Québec à Chicoutimi
  • Pierre-Luc Larouche Université du Québec à Chicoutimi
  • Isabelle Côté Université du Québec à Chicoutimi
  • Line Bouchard Université du Québec à Chicoutimi
  • André Pichette Université du Québec à Chicoutimi
  • Brian H Robinson The Hospital for Sick Children, Research Institute
  • Charles Morin Complexe hospitalier de la Sagamie, Chicoutimi

DOI:

https://doi.org/10.18433/J3M01X

Abstract

Abstract - Leigh syndrome French Canadian (LSFC) is a recessive disease caused by mutations in the LRPPRC gene (leucine-rich pentatricopeptide repeat containing protein). These mutations induce a cytochrome c oxidase (COX) deficiency resulting in episodes of acute acidotic crisis that will often lead to death. There is no effective treatment. Methylene blue (MB) is a redox dye that increases COX content and activity in vitro and in vivo suggesting that MB could prevent and treat LSFC. In this study, the protective effect of low-concentration MB was tested on two LSFC cell lines, including LSFC-F1, homozygous for the mutation A354V, and LSFC-F2 a compound heterozygous for the mutations A354V and C12775STOP. MB effect on metabolic activity was assessed on both LSFC cells in stable and acidotic conditions. For LSFC-F1, results showed that metabolic activity drastically decline after 96 hours in both conditions but not LSFC-F2 and normal cells. MB completely prevents the decrease of metabolic activity in LSFC-F1. Intracellular ATP content was also measured in both culture media. After 96 hours in acidotic medium, ATP content was almost completely depleted for both LSFC cells. Interestingly, MB completely restores ATP content in LSFC-F1 and LSFC-F2 cells. Finally, MB strongly improves the survival of both LSFC cells. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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Author Biographies

Jean Legault, Université du Québec à Chicoutimi

Department of fundamental sciences

Pierre-Luc Larouche, Université du Québec à Chicoutimi

Department of fundamental sciences

Isabelle Côté, Université du Québec à Chicoutimi

Department of fundamental sciences

Line Bouchard, Université du Québec à Chicoutimi

Department of fundamental sciences

André Pichette, Université du Québec à Chicoutimi

Department of fundamental sciences

Brian H Robinson, The Hospital for Sick Children, Research Institute

Department of Paediatrics

Charles Morin, Complexe hospitalier de la Sagamie, Chicoutimi

Department of Pediatrics and Clinical Research Unit

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Published

2011-12-02

How to Cite

Legault, J., Larouche, P.-L., Côté, I., Bouchard, L., Pichette, A., Robinson, B. H., & Morin, C. (2011). Low-Concentration Methylene Blue Maintains Energy Production and Strongly Improves Survival of Leigh Syndrome French Canadian Skin Fibroblasts. Journal of Pharmacy & Pharmaceutical Sciences, 14(3), 438–449. https://doi.org/10.18433/J3M01X

Issue

Section

Pharmaceutical Sciences; Review Articles