The E-domain region of mechano-growth factor inhibits cellular apoptosis and preserves cardiac function during myocardial infarctionReport as inadecuate




The E-domain region of mechano-growth factor inhibits cellular apoptosis and preserves cardiac function during myocardial infarction - Download this document for free, or read online. Document in PDF available to download.

Molecular and Cellular Biochemistry

, Volume 381, Issue 1–2, pp 69–83

First Online: 28 May 2013Received: 14 March 2013Accepted: 16 May 2013DOI: 10.1007-s11010-013-1689-4

Cite this article as: Mavrommatis, E., Shioura, K.M., Los, T. et al. Mol Cell Biochem 2013 381: 69. doi:10.1007-s11010-013-1689-4

Abstract

Insulin-like growth factor-1 IGF-1 isoforms are expressed via alternative splicing. Expression of the minor isoform IGF-1Eb also known as mechano-growth factor MGF is responsive to cell stress. Since IGF-1 isoforms differ in their E-domain regions, we are interested in determining the biological function of the MGF E-domain. To do so, a synthetic peptide analog was used to gain mechanistic insight into the actions of the E-domain. Treatment of H9c2 cells indicated a rapid cellular uptake mechanism that did not involve IGF-1 receptor activation but resulted in a nuclear localization. Peptide treatment inhibited the intrinsic apoptotic pathway in H9c2 cells subjected to cell stress with sorbitol by preventing the collapse of the mitochondrial membrane potential and inhibition of caspase-3 activation. Therefore, we administered the peptide at the time of myocardial infarction MI in mice. At 2 weeks post-MI cardiac function, gene expression and cell death were assayed. A significant decline in both systolic and diastolic function was evident in untreated mice based on PV loop analysis. Delivery of the E-peptide ameliorated the decline in function and resulted in significant preservation of cardiac contractility. Associated with these changes were an inhibition of pathologic hypertrophy and significantly fewer apoptotic nuclei in the viable myocardium of E-peptide-treated mice post-MI. We conclude that administration of the MGF E-domain peptide may provide a means of modulating local tissue IGF-1 autocrine-paracrine actions to preserve cardiac function, prevent cell death, and pathologic remodeling in the heart.

KeywordsIGF-1 isoforms E-domain Myocardial infarction Cardiac function Cell death Evangelos Mavrommatis and Krystyna M. Shioura contributed equally to this study.

Electronic supplementary materialThe online version of this article doi:10.1007-s11010-013-1689-4 contains supplementary material, which is available to authorized users.

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Author: Evangelos Mavrommatis - Krystyna M. Shioura - Tamara Los - Paul H. Goldspink

Source: https://link.springer.com/



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