Erythropoietin, the cytokine required for erythrocyte production, contributes to muscle progenitor cell proliferation and survival in culture and animal models. Erythropoietin induces transcription factors GATA-4 and TAL1 expression in myoblasts and knock down of GATA-4 or TAL1 changes myogenic regulatory factor expression program and promotes the myogenic differentiation. Sirtuin 1 activity, a NAD+ dependent deacetylation enzyme, myoblast cellular NAD+ level and NAD+/NADH ratio are increased by erythropoietin stimulation of C2C12 myoblasts. Sirtuin 1 knock down reduced GATA-4 and TAL1 expression and impaired the erythropoietin response suggesting that erythropoietin activity in myoblasts is mediated through GATA-4, TAL1 and Sirtuin 1. GATA-4 targets Sirtuin 1 to the myogenin promoter while TAL1 represses MyoD binding to and activation of the myogenin promoter. These data suggest a new pathway of erythropoietin activity in skeletal myoblasts affecting myogenic differentiation through cross-talk among Sirtuin1, GATA-4 and TAL1.

Project Start
Project End
Budget Start
Budget End
Support Year
37
Fiscal Year
2012
Total Cost
$362,920
Indirect Cost
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Reinhardt, Martin; Dey, Soumyadeep; Tom Noguchi, Constance et al. (2016) Non-hematopoietic effects of endogenous erythropoietin on lean mass and body weight regulation. Obesity (Silver Spring) 24:1530-6
Dey, Soumyadeep; Li, Xiaoxia; Teng, Ruifeng et al. (2016) Erythropoietin regulates POMC expression via STAT3 and potentiates leptin response. J Mol Endocrinol 56:55-67
Dey, Soumyadeep; Scullen, Tyler; Noguchi, Constance Tom (2015) Erythropoietin negatively regulates pituitary ACTH secretion. Brain Res 1608:14-20
Piknova, Barbora; Park, Ji Won; Swanson, Kathryn M et al. (2015) Skeletal muscle as an endogenous nitrate reservoir. Nitric Oxide 47:10-16
Alnaeeli, Mawadda; Raaka, Bruce M; Gavrilova, Oksana et al. (2014) Erythropoietin signaling: a novel regulator of white adipose tissue inflammation during diet-induced obesity. Diabetes 63:2415-31
Zhang, Yuanyuan; Wang, Li; Dey, Soumyadeep et al. (2014) Erythropoietin action in stress response, tissue maintenance and metabolism. Int J Mol Sci 15:10296-333
Park, Ji Won; Piknova, Barbora; Huang, Paul L et al. (2013) Effect of blood nitrite and nitrate levels on murine platelet function. PLoS One 8:e55699
Cokic, Vladan P; Smith, Reginald D; Biancotto, Angelique et al. (2013) Globin gene expression in correlation with G protein-related genes during erythroid differentiation. BMC Genomics 14:116
Wang, Li; Jia, Yi; Rogers, Heather et al. (2012) GATA-binding protein 4 (GATA-4) and T-cell acute leukemia 1 (TAL1) regulate myogenic differentiation and erythropoietin response via cross-talk with Sirtuin1 (Sirt1). J Biol Chem 287:30157-69
Alnaeeli, Mawadda; Wang, Li; Piknova, Barbora et al. (2012) Erythropoietin in brain development and beyond. Anat Res Int 2012:953264

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