Hypoxia decreases creatine uptake in cardiomyocytes, while creatine supplementation enhances HIF activation.

Journal Article (Journal Article)

Creatine (Cr), phosphocreatine (PCr), and creatine kinases (CK) comprise an energy shuttle linking ATP production in mitochondria with cellular consumption sites. Myocytes cannot synthesize Cr: these cells depend on uptake across the cell membrane by a specialized creatine transporter (CrT) to maintain intracellular Cr levels. Hypoxia interferes with energy metabolism, including the activity of the creatine energy shuttle, and therefore affects intracellular ATP and PCr levels. Here, we report that exposing cultured cardiomyocytes to low oxygen levels rapidly diminishes Cr transport by decreasing Vmax and Km Pharmacological activation of AMP-activated kinase (AMPK) abrogated the reduction in Cr transport caused by hypoxia. Cr supplementation increases ATP and PCr content in cardiomyocytes subjected to hypoxia, while also significantly augmenting the cellular adaptive response to hypoxia mediated by HIF-1 activation. Our results indicate that: (1) hypoxia reduces Cr transport in cardiomyocytes in culture, (2) the cytoprotective effects of Cr supplementation are related to enhanced adaptive physiological responses to hypoxia mediated by HIF-1, and (3) Cr supplementation increases the cellular ATP and PCr content in RNCMs exposed to hypoxia.

Full Text

Duke Authors

Cited Authors

  • Santacruz, L; Arciniegas, AJL; Darrabie, M; Mantilla, JG; Baron, RM; Bowles, DE; Mishra, R; Jacobs, DO

Published Date

  • August 2017

Published In

Volume / Issue

  • 5 / 16

PubMed ID

  • 28821596

Pubmed Central ID

  • PMC5582266

Electronic International Standard Serial Number (EISSN)

  • 2051-817X

Digital Object Identifier (DOI)

  • 10.14814/phy2.13382


  • eng

Conference Location

  • United States