Possible therapeutic effects of myxobacterial metabolites on type I Gaucher disease.

Abstract

Gaucher disease (GD) is the most prevalent lysosomal storage disorder caused by an inherited deficiency of glucocerebrosidase. In the present study, we aimed to determine whether myxobacterial metabolites exhibit a potential therapeutic effect in the cells from a patient with type I GD. We screened 288 bioactive compounds of myxobacteria in the skin fibroblasts from a patient with type I GD. MTT assays were performed to determine their effects on cell viability. The expression levels of Bcl-2-associated X protein (Bax), ATP-citrate synthase (ATP-CS), E3-binding protein (E3BP), and acetyl-coenzyme A acetyltransferase 1 (ACAT1) were determined by western blotting to understand the molecular mechanisms of myxobacterial metabolites in cells. Thin-layer chromatography (TLC) was carried out to measure changes in glucosylceramide levels in the cultured fibroblasts. This screening process identified 4 compounds that increased cell viability more than 1.45 times. After exposure to these compounds, the expression level of Bax decreased, whereas those of ATP-CS, E3BP, and ACAT1 increased. TLC revealed reduced amounts of intracellular glucosylceramides in patient cells. Here we suggest that myxobacterial metabolites can relieve the stress due to glucosylceramide accumulation, and that it may be utilized as a new therapeutic approach.

• Authors: Sung-Jo Kim, Sunyang Kang, June-Bum Kim
• Journal: Gene (Gene) Vol. 504 Issue 2 Pg. 156-9 (Aug 10 2012) ISSN: 1879-0038 [Electronic] Netherlands
• PMID: 22634098 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Bacterial Proteins
• PDHX protein, human
• Pyruvate Dehydrogenase Complex
• bcl-2-Associated X Protein
• ACAT1 protein, human
• Acetyl-CoA C-Acetyltransferase
• ATP Citrate (pro-S)-Lyase

Topics

• ATP Citrate (pro-S)-Lyase (metabolism)
• Acetyl-CoA C-Acetyltransferase (metabolism)
• Bacterial Proteins (therapeutic use)
• Blotting, Western
• Cell Division
• Cells, Cultured
• Chromatography, Thin Layer
• Gaucher Disease (metabolism, pathology, therapy)
• Humans
• Myxococcales (metabolism)
• Pyruvate Dehydrogenase Complex (metabolism)
• bcl-2-Associated X Protein (metabolism)