Involvement of UTP in protection of cardiomyocytes from hypoxic stress

Asher Shainberg, Smadar Yitzhaki, Or Golan, Kenneth A. Jacobson, Edith Hochhauser

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Massive amounts of nucleotides are released during ischemia in the cardiovascular system. Although the effect of the purine nucleotide ATP has been intensively studied in myocardial infarction, the cardioprotective role of the pyrimi- dine nucleotide UTP is still unclear, especially in the cardiovascular system. The purpose of our study was to elucidate the protective effects of UTP receptor activation and describe the downstream cascade for the cardioprotective effect. Cultured cardiomyocytes and left anterior descending (LAD)-ligated rat hearts were pretreated with UTP and exposed to hypoxia- ischemia. In vitro experiments revealed that UTP reduced cardiomyocyte death induced by hypoxia, an effect that was diminished by suramin. UTP caused several effects that could trigger a cardioprotective response: a transient increase of [Ca 2+]i, an effect that was abolished by PPADS or RB2; phosphorylation of the kinases ERK and Akt, which was abolished by U0126 and LY294002, respectively; and reduced mitochondrial calcium elevation after hypoxia. In vivo experiments revealed that UTP maintained ATP levels, improved mitochondrial activity, and reduced infarct size. In conclusion, UTP administrated before ischemia reduced infarct size and improved myocardial function. Reduction of mitochondrial calcium overload can partially explain the protective effect of UTP after hypoxic-ischemic injury.

Original languageEnglish
Pages (from-to)287-299
Number of pages13
JournalCanadian Journal of Physiology and Pharmacology
Issue number4
StatePublished - Apr 2009


FundersFunder number
National Institute of Diabetes and Digestive and Kidney DiseasesZIADK031116


    • Calcium
    • Cardiac cell culture
    • Cardioprotection
    • Heart
    • Hypoxia
    • Ischemia
    • Nucleotides
    • Preconditioning
    • Pyrimi- Dines


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