Title

Factors released from embryonic stem cells inhibit apoptosis of H9c2 cells

Authors

Authors

D. K. Singla;D. E. McDonald

Comments

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Abbreviated Journal Title

Am. J. Physiol.-Heart Circul. Physiol.

Keywords

hydrogen peroxide; tissue inhibitor of metalloproteinase-1; BREAST EPITHELIAL-CELLS; MYOCARDIAL-INFARCTION; TISSUE INHIBITOR; OXIDATIVE STRESS; GROWTH-FACTORS; HEART-FAILURE; DEATH; TRANSPLANTATION; DIFFERENTIATION; CARDIOMYOCYTES; Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular; Disease

Abstract

suggests that transplanted embryonic stem (ES) cells subsequent to myocardial infarction differentiate into the major cell types in the heart and improve cardiac function. However, the extent of regeneration is relatively meager compared with the observed functional improvement. The mechanisms underlying their improved function are completely unknown. In this report, we provide evidence using a cell culture model system for novel mechanisms that involve the release of cytoprotective, antiapoptotic factor(s) from ES cells and inhibit H2O2-induced apoptosis in the rat cardiomyocyte-derived cell line H9c2. Conditioned medium (CM) from growing mouse ES cells treated with and without H2O2 was generated. Apoptosis was induced after exposure to H2O2 in H9c2 cells for 2 h followed by replacement with fresh cell culture or ES cell-CM. After 24 h, H9c2 cells treated with both ES cell-CMs demonstrated significantly decreased apoptosis, as determined by terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling staining, apoptotic ELISA, caspase-3 activity, and DNA ladder. Next, using Luminex technology, we examined the presence of antiapoptotic proteins cystatin c, osteopontin, and clusterin and anti-fibrotic, tissue inhibitor of metalloproteinase-1 (TIMP-1) in both ES cell-CMs. The levels of released factors were 2- to 170-fold higher than those in H9c2 cell-CM. Antiapoptotic effects of ES cell-CM were significantly inhibited with TIMP-1 antibody, suggesting that TIMP-1 is an important factor to inhibit apoptosis. Furthermore, we used CM from an TIMP-1-overexpressing cell line and demonstrated that H2O2-induced apoptosis in the H9c2 cells was significantly inhibited. These observations demonstrate that factors released from ES cells contain antiapoptotic factors and that the effects are mediated by TIMP-1. Moreover, these findings suggest that released factors might be useful for therapeutic applications in ischemic heart disease as well as for many other diseases.

Journal Title

American Journal of Physiology-Heart and Circulatory Physiology

Volume

293

Issue/Number

3

Publication Date

1-1-2007

Document Type

Article

Language

English

First Page

H1590

Last Page

H1595

WOS Identifier

WOS:000249237800035

ISSN

0363-6135

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