modeling-myotonic-dystrophy-1-in-c2c12-myoblast-cells

Modeling Myotonic Dystrophy 1 in C2C12 Myoblast Cells

Myotonic dystrophy 1 (DM1) is a common form of muscular dystrophy. Although several animal models have been established for DM1, myoblast cell models are ...

University of Houston

The First Affiliated Hospital of Nanchang University

In order to search for structurally novel and bioactive natural compounds from marine-derived fungi, a halotolerant fungal strain (THW-18) identified as Alternaria raphani was isolated from sediment collected in the Hongdao sea salt field. From the ethyl acetate extract of Alternaria raphani, three new cerebrosides, alternarosides A-C (1-3), and a new diketopiperazine alkaloid, alternarosin A (4), together with 15 known compounds were isolated and identified by spectroscopic and chemical methods, as well as X-ray crystal diffraction analysis. Compounds 1-4 showed weak antibacterial activity against Escherichia coli, Bacillus subtilis, and Candida albicans with MIC values ranging from 70 to 400 muM.

Cerebrosides of the halotolerant fungus Alternaria raphani isolated from a sea salt field.

Two novel cyclic hexapeptides containing both anthranilic acid and dehydroamino acid units, sclerotides A (1) and B (2), were isolated from the marine-derived halotolerant Aspergillus sclerotiorum PT06-1 in a nutrient-limited hypersaline medium. Both 1 and 2 are photointerconvertible and could be interconverted via a radical reaction initiated by direct photoisomerization. Both compounds showed moderate antifungal activity. Compound 2 also showed weak cytotoxicity and antibacterial activity.

Novel cyclic hexapeptides from marine-derived fungus, Aspergillus sclerotiorum PT06-1.

Five new cerebrosides, chrysogesides A-E (1-5), and two new 2-pyridone alkaloids, chrysogedones A and B (6 and 7), were isolated from the fermentation broth of Penicillium chrysogenum PXP-55, a halotolerant fungus grown in a hypersaline medium. Among them, chrysogesides B-D (2-4) are the first cerebrosides that contain an unsaturated C(19)-fatty acid. Their structures were identified by spectroscopic and chemical methods, including CD spectroscopy as well as the modified Mosher's method. Compound 2 showed antimicrobial activity against Enterobacter aerogenes with an MIC value of 1.72 μM.

Cerebrosides and 2-pyridone alkaloids from the halotolerant fungus Penicillium chrysogenum grown in a hypersaline medium.

Myotonic dystrophy is a neuromuscular disease of RNA toxicity. The disease gene DMPK harbors expanded CTG trinucleotide repeats on its 3'-UTR. The transcripts of this mutant DMPK led to misregulation of RNA-binding proteins including MBNL1 and Celf1. In myoblasts, CUG-expansion impaired terminal differentiation. In this study, we formally tested how the abundance of Celf1 regulates normal myocyte differentiation, and how Celf1 expression level mediates CUG-expansion RNA toxicity-triggered impairment of myocyte differentiation. As the results, overexpression of Celf1 largely recapitulated the defects of myocytes with CUG-expansion, by increasing myocyte cycling. Knockdown of endogenous Celf1 level led to precocious myotube formation, supporting a negative connection between Celf1 abundance and myocyte terminal differentiation. Finally, knockdown of Celf1 in myocyte with CUG-expansion led to partial rescue, by promoting cell cycle exit. Our results suggest that Celf1 plays a distinctive and negative role in terminal myocyte differentiation, which partially contribute to DM1 RNA toxicity. Targeting Celf1 may be a valid strategy in correcting DM1 muscle phenotypes, especially for congenital cases.

Article	Year
Cerebrosides of the halotolerant fungus Alternaria raphani isolated from a sea salt field. Journal of natural products\| PubMed ID: 19685913	2009
Novel cyclic hexapeptides from marine-derived fungus, Aspergillus sclerotiorum PT06-1. Organic letters\| PubMed ID: 19827766	2009
Cerebrosides and 2-pyridone alkaloids from the halotolerant fungus Penicillium chrysogenum grown in a hypersaline medium. Journal of natural products\| PubMed ID: 21381678	2011
Celf1 regulates cell cycle and is partially responsible for defective myoblast differentiation in myotonic dystrophy RNA toxicity. Biochimica et biophysica acta\| PubMed ID: 25887157	2015

Xiaoping Peng

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