Insulin-like Growth Factor Binding Protein-3 Mediates Serum Starvation- and Doxorubicin-induced Apoptosis in H9c2 Cardiac Cells

Overview

Journal J Endocrinol Invest

Publisher Springer

Specialty Endocrinology

Date 2004 Apr 2

PMID 15055478

Citations 6

Authors

R Granata

M De Petrini

L Trovato

R Ponti

N Pons

C Ghe

A Graziani

R J Ferry Jr

G Muccioli

E Ghigo

Affiliations

Soon will be listed here.

Abstract

Insulin-like growth factor binding protein 3 (IGFBP-3) modulates the activity of IGF-I, which exerts antiapoptotic action upon the myocardiocyte. IGFBP-3 also exerts IGF-independent actions to inhibit cell growth and induce apoptosis, mediating the effects of several antiproliferative agents. We hypothesized that IGFBP-3 mediates cardiomyocyte apoptosis. IGFBP-3 expression was studied in H9c2 rat cardiac cells cultured in serum-deprived medium in the absence or presence of 1 microM doxorubicin during a 72 h time-span. To a greater degree than serum withdrawal, doxorubicin induced IGFBP-3 up-regulation that was time-dependent. IGFBP-3 mRNA levels positively correlated with the degree of apoptosis. Exogenous IGFBP-3 decreased cell viability and induced apoptosis in serum-starved cells exposed to doxorubicin. IGFBP-3 antisense oligonucleotides markedly decreased apoptosis induced by either serum withdrawal or doxorubicin. Binding studies revealed specific high-affinity sites for IGFBP-3 in H9c2 cardiomyocytes, with binding characteristics typical of receptor-ligand interactions. These findings indicate that IGFBP-3 could play proapoptotic action at the myocardial level and suggest a novel role for this protein in cardiovascular dysfunction.

Citing Articles

Integrative transcriptomics and cell systems analyses reveal protective pathways controlled by Igfbp-3 in anthracycline-induced cardiotoxicity.

Chen J, Chapski D, Jong J, Awada J, Wang Y, Slamon D FASEB J. 2023; 37(6):e22977.

PMID: 37219486 PMC: 10286824. DOI: 10.1096/fj.202201885RR.

Involvement of p53 in insulin-like growth factor binding protein-3 regulation in the breast cancer cell response to DNA damage.

Marzec K, Lin M, Martin J, Baxter R Oncotarget. 2015; 6(29):26583-98.

PMID: 26378048 PMC: 4694938. DOI: 10.18632/oncotarget.5612.

Nuclear actions of insulin-like growth factor binding protein-3.

Baxter R Gene. 2015; 569(1):7-13.

PMID: 26074086 PMC: 4496269. DOI: 10.1016/j.gene.2015.06.028.

Doxorubicin impairs the insulin-like growth factor-1 system and causes insulin-like growth factor-1 resistance in cardiomyocytes.

Fabbi P, Spallarossa P, Garibaldi S, Barisione C, Mura M, Altieri P PLoS One. 2015; 10(5):e0124643.

PMID: 25955698 PMC: 4425434. DOI: 10.1371/journal.pone.0124643.

Involvement of the insulin-like growth factor binding proteins in the cancer cell response to DNA damage.

Chua M, Lin M, Martin J, Baxter R J Cell Commun Signal. 2015; 9(2):167-76.

PMID: 25617051 PMC: 4458249. DOI: 10.1007/s12079-015-0262-1.

References

Perks C, McCaig C, Holly J . Differential insulin-like growth factor (IGF)-independent interactions of IGF binding protein-3 and IGF binding protein-5 on apoptosis in human breast cancer cells. Involvement of the mitochondria. J Cell Biochem. 2000; 80(2):248-58. DOI: 10.1002/1097-4644(20010201)80:2<248::aid-jcb140>3.0.co;2-4. View

Phillips L, Pao C, Villafuerte B . Molecular regulation of insulin-like growth factor-I and its principal binding protein, IGFBP-3. Prog Nucleic Acid Res Mol Biol. 1998; 60:195-265. DOI: 10.1016/s0079-6603(08)60894-6. View

Maclellan W, Schneider M . Death by design. Programmed cell death in cardiovascular biology and disease. Circ Res. 1997; 81(2):137-44. DOI: 10.1161/01.res.81.2.137. View

Kimes B, Brandt B . Properties of a clonal muscle cell line from rat heart. Exp Cell Res. 1976; 98(2):367-81. DOI: 10.1016/0014-4827(76)90447-x. View

Gill Z, Perks C, Newcomb P, Holly J . Insulin-like growth factor-binding protein (IGFBP-3) predisposes breast cancer cells to programmed cell death in a non-IGF-dependent manner. J Biol Chem. 1997; 272(41):25602-7. DOI: 10.1074/jbc.272.41.25602. View

Baldanzi G, Filigheddu N, Cutrupi S, Catapano F, Bonissoni S, Fubini A . Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT. J Cell Biol. 2002; 159(6):1029-37. PMC: 2173981. DOI: 10.1083/jcb.200207165. View

Wang L, Ma W, Markovich R, Lee W, Wang P . Insulin-like growth factor I modulates induction of apoptotic signaling in H9C2 cardiac muscle cells. Endocrinology. 1998; 139(3):1354-60. DOI: 10.1210/endo.139.3.5801. View

Yamanaka Y, Fowlkes J, Wilson E, Rosenfeld R, Oh Y . Characterization of insulin-like growth factor binding protein-3 (IGFBP-3) binding to human breast cancer cells: kinetics of IGFBP-3 binding and identification of receptor binding domain on the IGFBP-3 molecule. Endocrinology. 1999; 140(3):1319-28. DOI: 10.1210/endo.140.3.6566. View

Francis G, ROSS M, Ballard F, Milner S, Senn C, McNeil K . Novel recombinant fusion protein analogues of insulin-like growth factor (IGF)-I indicate the relative importance of IGF-binding protein and receptor binding for enhanced biological potency. J Mol Endocrinol. 1992; 8(3):213-23. DOI: 10.1677/jme.0.0080213. View

10.

Grimberg A, Liu B, Bannerman P, El-Deiry W, Cohen P . IGFBP-3 mediates p53-induced apoptosis during serum starvation. Int J Oncol. 2002; 21(2):327-35. PMC: 4152903. View

11.

Hong J, Zhang G, Dong F, Rechler M . Insulin-like growth factor (IGF)-binding protein-3 mutants that do not bind IGF-I or IGF-II stimulate apoptosis in human prostate cancer cells. J Biol Chem. 2002; 277(12):10489-97. DOI: 10.1074/jbc.M109604200. View

12.

Derenne S, Monia B, Dean N, Taylor J, Rapp M, Harousseau J . Antisense strategy shows that Mcl-1 rather than Bcl-2 or Bcl-x(L) is an essential survival protein of human myeloma cells. Blood. 2002; 100(1):194-9. DOI: 10.1182/blood.v100.1.194. View

13.

Zadeh S, BINOUX M . The 16-kDa proteolytic fragment of insulin-like growth factor (IGF) binding protein-3 inhibits the mitogenic action of fibroblast growth factor on mouse fibroblasts with a targeted disruption of the type 1 IGF receptor gene. Endocrinology. 1997; 138(7):3069-72. DOI: 10.1210/endo.138.7.5380. View

14.

Hescheler J, Meyer R, Plant S, Krautwurst D, Rosenthal W, Schultz G . Morphological, biochemical, and electrophysiological characterization of a clonal cell (H9c2) line from rat heart. Circ Res. 1991; 69(6):1476-86. DOI: 10.1161/01.res.69.6.1476. View

15.

Hwa V, Oh Y, Rosenfeld R . The insulin-like growth factor-binding protein (IGFBP) superfamily. Endocr Rev. 1999; 20(6):761-87. DOI: 10.1210/edrv.20.6.0382. View

16.

Knudtson K, Boes M, Sandra A, Dake B, BOOTH B, Bar R . Distribution of chimeric IGF binding protein (IGFBP)-3 and IGFBP-4 in the rat heart: importance of C-terminal basic region. Endocrinology. 2001; 142(9):3749-55. DOI: 10.1210/endo.142.9.8353. View

17.

Oh Y, Muller H, Pham H, Rosenfeld R . Demonstration of receptors for insulin-like growth factor binding protein-3 on Hs578T human breast cancer cells. J Biol Chem. 1993; 268(35):26045-8. View

18.

Kalyanaraman B, Joseph J, Kalivendi S, Wang S, Konorev E, Kotamraju S . Doxorubicin-induced apoptosis: implications in cardiotoxicity. Mol Cell Biochem. 2002; 234-235(1-2):119-24. View

19.

Gibson U, Heid C, Williams P . A novel method for real time quantitative RT-PCR. Genome Res. 1996; 6(10):995-1001. DOI: 10.1101/gr.6.10.995. View

20.

Delpy E, Hatem S, Andrieu N, de Vaumas C, Henaff M, Rucker-Martin C . Doxorubicin induces slow ceramide accumulation and late apoptosis in cultured adult rat ventricular myocytes. Cardiovasc Res. 1999; 43(2):398-407. DOI: 10.1016/s0008-6363(99)00142-x. View