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Exp Cell Res. 2004 Dec 10;301(2):320-30.

MIBG, an inhibitor of arginine-dependent mono(ADP-ribosyl)ation, prevents differentiation of L6 skeletal myoblasts by inhibiting expression of myogenin and p21(cip1).

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  • 1Department of Physiology, University of Manitoba, Canada R3E 3J7.

Abstract

The development of skeletal muscle is controlled by a highly synchronized series of cellular events, and various signals from both inside and outside the cell play a role in the switch from multipotential mesodermal stem cells to muscle fibers. Meta-iodobenzylguanidine (MIBG), an inhibitor of mono(ADP-ribosyl)ation, has been shown to prevent terminal differentiation of skeletal myoblasts; however, its mechanism of action has not been established. We recently reported that MIBG is capable of preventing phenotypic modulation of smooth muscle cells by interfering with specific trans-acting factors [L. Yau, B. Litchie, S. Thomas, B. Storie, N. Yurkova, P. Zahradka, Endogenous mono-ADP-ribosylation mediates smooth muscle cell proliferation and migration via protein kinase N-dependent induction of c-fos expression. Eur. J. Biochem. 270 (2003) 101-110.]. We therefore examined the effect of MIBG on select myogenic regulatory factors known to control terminal differentiation. It was confirmed that MIBG, but not inhibitors of poly-ADP-ribose polymerase (3-aminobenzamide, PD128763), inhibits fusion of L6 skeletal myoblasts in a concentration-dependent manner. Moreover, inhibition by MIBG correlated with a failure to induce expression of myogenin and p21(cip1), while levels of MyoD and MEF2 were unaffected. Time-of-addition studies revealed that MIBG also affected a late event possibly linked to cell fusion. Finally, arginine-dependent mono(ADP-ribosyl)transferase activity increased over the first 24 h of the differentiation period. These data support a role for arginine-dependent mono(ADP-ribosyl)transferase as an essential positive regulator of differentiation in skeletal muscle cells that operates by modulating the expression of specific myogenic factors.

PMID:
15530866
[PubMed - indexed for MEDLINE]
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