The fully linked HTML version of this article has now been published.
JCS ePress
online publication date 9 Mar 2004
doi: 10.1242/jcs.01028
Research Article
Partitioning of IGFBP-5 actions in myogenesis: IGF-independent anti-apoptotic function
Laura J. Cobb,
Dervis A.M. Salih,
Ivelisse Gonzalez,
Gyanendra Tripathi,
Emma J. Carter,
Fiona Lovett,
Cathy Holding,
and
Jennifer M. Pell*
* Author for correspondence (e-mail: jenny.pell{at}bbsrc.ac.uk)
Igfbp5 is upregulated during the differentiation of several key cell lineages and in some tumours; the function of IGFBP-5 in these physiological and pathological situations is unknown. Since IGFBP-5 contains sequence motifs consistent with IGF-independent actions, the aim of these studies was to distinguish between IGF-dependent and -independent actions of IGFBP-5. Myc-tagged wild-type (termed wtIGFBP-5) and non-IGF binding mouse Igfbp5 (termed mutIGFBP-5) cDNAs were generated and used to transfect C2 myoblasts, a cell line that undergoes differentiation to myotubes in an IGF- and IGFBP-5-regulated manner. WtIGFBP-5, but not mutIGFBP-5, inhibited myogenesis, as assessed by cell morphology, MHC immunocytochemistry and caveolin 3 expression. However, both wt- and mutIGFBP-5 increased cell survival and decreased apoptosis, as indicated by decreased caspase-3 activity and cell surface annexin V binding. Further examination of apoptotic pathways revealed that wt- and mutIGFBP-5 ameliorated the increase in caspase-9 but not the modest increase in caspase-8 during myogenesis, suggesting that IGFBP-5 increased cell survival via inhibition of intrinsic cell death pathways in an IGF-independent manner. The relationship between IGF-II and IGFBP-5 was examined further by cotransfecting C2 myoblasts with antisense Igf2 (previously established to induce increased cell death) and Igfbp5; both wt- and mutIGFBP-5 conferred equivalent protection against the decreased cell survival and increased apoptosis. In conclusion, we have partitioned IGFBP-5 action in myogenesis into IGF-dependent inhibition of differentiation and IGF-independent cell survival. Our findings suggest that, by regulation of cell survival, IGFBP-5 has an autonomous role in the regulation of cell fate in development and in tumourigenesis.
This article has been cited by other articles:
|
|
|
|
 
H. Ren, P. Yin, and C. Duan
IGFBP-5 regulates muscle cell differentiation by binding to IGF-II and switching on the IGF-II auto-regulation loop
J. Cell Biol.,
September 8, 2008;
182(5):
979 - 991.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Al-Shanti and C. E Stewart
PD98059 enhances C2 myoblast differentiation through p38 MAPK activation: a novel role for PD98059
J. Endocrinol.,
July 1, 2008;
198(1):
243 - 252.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. R. Dayton and M. E. White
Cellular and molecular regulation of muscle growth and development in meat animals
J Anim Sci,
April 1, 2008;
86(14_suppl):
E217 - E225.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Mukherjee, E. M. Wilson, and P. Rotwein
Insulin-Like Growth Factor (IGF) Binding Protein-5 Blocks Skeletal Muscle Differentiation by Inhibiting IGF Actions
Mol. Endocrinol.,
January 1, 2008;
22(1):
206 - 215.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. S. Kim, Y. B. Seu, S.-H. Baek, M. J. Kim, K. J. Kim, J. H. Kim, and J.-R. Kim
Induction of Cellular Senescence by Insulin-like Growth Factor Binding Protein-5 through a p53-dependent Mechanism
Mol. Biol. Cell,
November 1, 2007;
18(11):
4543 - 4552.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Mazroui, S. Di Marco, R. J. Kaufman, and I.-E. Gallouzi
Inhibition of the Ubiquitin-Proteasome System Induces Stress Granule Formation
Mol. Biol. Cell,
July 1, 2007;
18(7):
2603 - 2618.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A M Solomon and P M G Bouloux
Modifying muscle mass - the endocrine perspective.
J. Endocrinol.,
November 1, 2006;
191(2):
349 - 360.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Zhao, P. Yin, L. A. Bach, and C. Duan
Several Acidic Amino Acids in the N-domain of Insulin-like Growth Factor-binding Protein-5 Are Important for Its Transactivation Activity
J. Biol. Chem.,
May 19, 2006;
281(20):
14184 - 14191.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. H. Lang, B. J. Krawiec, D. Huber, J. M. McCoy, and R. A. Frost
Sepsis and inflammatory insults downregulate IGFBP-5, but not IGFBP-4, in skeletal muscle via a TNF-dependent mechanism
Am J Physiol Regulatory Integrative Comp Physiol,
April 1, 2006;
290(4):
R963 - R972.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Granado, T. Priego, A. I. Martin, M{a} A. Villanua, and A. Lopez-Calderon
Ghrelin receptor agonist GHRP-2 prevents arthritis-induced increase in E3 ubiquitin-ligating enzymes MuRF1 and MAFbx gene expression in skeletal muscle
Am J Physiol Endocrinol Metab,
December 1, 2005;
289(6):
E1007 - E1014.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M S Pampusch, G Xi, E Kamanga-Sollo, K J Loseth, M R Hathaway, W R Dayton, and M E White
Production of recombinant porcine IGF-binding protein-5 and its effect on proliferation of porcine embryonic myoblast cultures in the presence and absence of IGF-I and Long-R3-IGF-I
J. Endocrinol.,
April 1, 2005;
185(1):
197 - 206.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. M. Salih, S. Mohan, Y. Kasukawa, G. Tripathi, F. A. Lovett, N. F. Anderson, E. J. Carter, J. E. Wergedal, D. J. Baylink, and J. M. Pell
Insulin-Like Growth Factor-Binding Protein-5 Induces a Gender-Related Decrease in Bone Mineral Density in Transgenic Mice
Endocrinology,
February 1, 2005;
146(2):
931 - 940.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Yin, Q. Xu, and C. Duan
Paradoxical Actions of Endogenous and Exogenous Insulin-like Growth Factor-binding Protein-5 Revealed by RNA Interference Analysis
J. Biol. Chem.,
July 30, 2004;
279(31):
32660 - 32666.
[Abstract]
[Full Text]
[PDF]
|
|
|
© The Company of Biologists Ltd 2004
