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Title: The prelamin A pre-peptide induces cardiac and skeletal myoblast differentiation

Abstract

Prelamin A processing is unique amongst mammalian proteins and results in the production of a farnesylated and carboxymethylated peptide. We examined the effect of pathogenic LMNA mutations on prelamin A processing, and of the covalently modified peptide on cardiac and skeletal myoblast differentiation. Here we report a mutation associated with dilated cardiomyopathy prevents prelamin A peptide production. In addition, topical application of the covalently modified C-terminal peptide to proliferating skeletal and cardiac myoblasts induced myotube and striated tissue formation, respectively. Western blot analysis revealed that skeletal and cardiac myoblasts are the first cell lines examined to contain unprocessed prelamin A, and immunostaining of peptide-treated cells revealed a previously unidentified role for prelamin A in cytoskeleton formation and intercellular organization. These results demonstrate a direct role for prelamin A in myoblast differentiation and indicate the prelamin A peptide may have therapeutic potential.

Authors:
 [1];  [2];  [2];  [2];  [3]
  1. Division of Medical Oncology, Department of Medicine, University of Colorado at Denver and Health Sciences Center, Denver, CO 80262 (United States). E-mail: Gary.Brodsky@uchsc.edu
  2. Division of Medical Oncology, Department of Medicine, University of Colorado at Denver and Health Sciences Center, Denver, CO 80262 (United States)
  3. Department of Pediatrics, University of Colorado at Denver and Health Sciences Center, Denver, CO 80262 (United States)
Publication Date:
OSTI Identifier:
20991342
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 356; Journal Issue: 4; Other Information: DOI: 10.1016/j.bbrc.2007.03.062; PII: S0006-291X(07)00527-X; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; MAMMALS; MICROTUBULES; MUTATIONS; MYOBLASTS; PEPTIDES

Citation Formats

Brodsky, Gary L., Bowersox, Jeffrey A., Fitzgerald-Miller, Lisa, Miller, Leslie A., and Maclean, Kenneth N. The prelamin A pre-peptide induces cardiac and skeletal myoblast differentiation. United States: N. p., 2007. Web. doi:10.1016/j.bbrc.2007.03.062.
Brodsky, Gary L., Bowersox, Jeffrey A., Fitzgerald-Miller, Lisa, Miller, Leslie A., & Maclean, Kenneth N. The prelamin A pre-peptide induces cardiac and skeletal myoblast differentiation. United States. doi:10.1016/j.bbrc.2007.03.062.
Brodsky, Gary L., Bowersox, Jeffrey A., Fitzgerald-Miller, Lisa, Miller, Leslie A., and Maclean, Kenneth N. Fri . "The prelamin A pre-peptide induces cardiac and skeletal myoblast differentiation". United States. doi:10.1016/j.bbrc.2007.03.062.
@article{osti_20991342,
title = {The prelamin A pre-peptide induces cardiac and skeletal myoblast differentiation},
author = {Brodsky, Gary L. and Bowersox, Jeffrey A. and Fitzgerald-Miller, Lisa and Miller, Leslie A. and Maclean, Kenneth N.},
abstractNote = {Prelamin A processing is unique amongst mammalian proteins and results in the production of a farnesylated and carboxymethylated peptide. We examined the effect of pathogenic LMNA mutations on prelamin A processing, and of the covalently modified peptide on cardiac and skeletal myoblast differentiation. Here we report a mutation associated with dilated cardiomyopathy prevents prelamin A peptide production. In addition, topical application of the covalently modified C-terminal peptide to proliferating skeletal and cardiac myoblasts induced myotube and striated tissue formation, respectively. Western blot analysis revealed that skeletal and cardiac myoblasts are the first cell lines examined to contain unprocessed prelamin A, and immunostaining of peptide-treated cells revealed a previously unidentified role for prelamin A in cytoskeleton formation and intercellular organization. These results demonstrate a direct role for prelamin A in myoblast differentiation and indicate the prelamin A peptide may have therapeutic potential.},
doi = {10.1016/j.bbrc.2007.03.062},
journal = {Biochemical and Biophysical Research Communications},
number = 4,
volume = 356,
place = {United States},
year = {Fri May 18 00:00:00 EDT 2007},
month = {Fri May 18 00:00:00 EDT 2007}
}
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