Factors released from embryonic stem cells inhibit apoptosis in H9c2 cells through PI3K/Akt but not ERK pathway

    Authors

    D. K. Singla; R. D. Singla;D. E. McDonald

    Comments

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    Abbreviated Journal Title

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

    Keywords

    hydrogen peroxide; phosphatidylinositol 3-kinase; extracellular; signal-regulated kinase; SIGNAL-TRANSDUCTION PATHWAYS; BREAST EPITHELIAL-CELLS; OXIDATIVE STRESS; MYOCARDIAL-INFARCTION; PHOSPHATIDYLINOSITOL 3-KINASE; PHOSPHOINOSITIDE; 3-KINASE; H2O2-INDUCED APOPTOSIS; CARDIOMYOCYTE SURVIVAL; FUNCTIONAL; IMPROVEMENT; VENTRICULAR MYOCYTES; Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular; Disease

    Abstract

    We recently reported that embryonic stem cells-conditioned medium (ES-CM) contains antiapoptotic factors that inhibit apoptosis in the cardiac myoblast H9c2 cells. However, the mechanisms of inhibited apoptosis remain elusive. In this report, we provide evidence for the novel mechanisms involved in the inhibition of apoptosis provided by ES-CM. ES-CM from mouse ES cells was generated. Apoptosis was induced after exposure with H2O2 (400 mu m) in H9c2 cells followed by the replacement with ES-CM or culture medium. H9c2 cells treated with H2O2 were exposed to ES-CM, and ES-CM plus cell survival protein phosphatidylinositol 3-kinase/Akt inhibitor, LY-294002, or extracellular signal-regulated kinase (ERK1/2) inhibitor, PD-98050. After 24 h, H9c2 cells treated with ES-CM demonstrated a significant increase in cell survival. ES-CM significantly inhibited (P < 0.05) apoptosis determined by terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling staining, apoptotic ELISA, and caspase-3 activity. Importantly, enhanced cell survival and inhibited apoptosis with ES-CM was abolished with LY-294002. In contrast, PD-98050 shows no effect on ES-CM-increased cell survival. Furthermore, H2O2-induced apoptosis is associated with decreased levels of phosphorylated (p)Akt activity. Following treatment with ES-CM, we observed a decrease in apoptosis with an increase in pAkt, and the increased activity was attenuated with the Akt inhibitor, suggesting that the Akt pathway is involved in the decreased apoptosis and cell survival provided by ES-CM. In contrast, we observed no change in ES-CM-decreased apoptosis or pERK with PD-98050. In conclusion, we suggest that ES-CM inhibited apoptosis and is mediated by Akt but not the ERK pathway.

    Journal Title

    American Journal of Physiology-Heart and Circulatory Physiology

    Volume

    295

    Issue/Number

    2

    Publication Date

    1-1-2008

    Document Type

    Article

    Language

    English

    First Page

    H907

    Last Page

    H913

    WOS Identifier

    WOS:000258254200054

    ISSN

    0363-6135

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