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UTP but not ATP causes hypertrophic growth in neonatal rat cardiomyocytes
Tam M Pham1, James B Morris, Jane F Arthur
1Cellular Biochemistry Laboratory, Baker Heart Research Institute, PO Box 6492, St. Kilda Road, Central, Vic. 8008, Melbourne, Australia.
Abstract:
Addition of ATP to neonatal rat cardiomyocytes has been reported to inhibit hypertrophic growth responses, even though G(q)-coupled receptors are activated. In the current study, we investigated hypertrophic responses to activation of G(q)-coupled-purinergic receptors on cardiomyocytes using UTP as an alternative agonist to ATP. UTP (100 microM) activated phospholipase C via G(q) similarly to ATP, and responses to the two agonists were not additive. Similarly, UTP and ATP both induced phosphorylation of extracellular signal-regulated kinase (ERK1/2), while having little effect on p38 mitogen-activated protein kinase or c-Jun NH(2)-terminal kinase. However, addition of UTP (100 microM) to cardiomyocytes caused hypertrophic growth indicated by increased protein content without DNA synthesis. ATP (100 microM) caused no increase in protein. We conclude that activation of purinergic receptors on neonatal cardiomyocytes initiates hypertrophic signaling pathways, but that prolonged exposure to ATP, but not UTP, has growth-inhibitory effects.
Insights
Adenosine triphosphate (ATP) and uridine triphosphate (UTP) activate G(q)-coupled purinergic receptors in neonatal rat cardiomyocytes. While UTP promotes hypertrophic growth, ATP inhibits it, suggesting differential signaling outcomes.
Area of Science:
- Cardiology
- Cellular Biology
- Biochemistry
Background:
- Neonatal rat cardiomyocytes exhibit inhibited hypertrophic growth upon ATP addition, despite G(q)-coupled receptor activation.
- Purinergic receptors play a role in cellular signaling pathways within cardiomyocytes.
Purpose of the Study:
- To investigate the hypertrophic responses of cardiomyocytes to G(q)-coupled purinergic receptor activation using UTP as an agonist.
- To compare the effects of UTP and ATP on cardiomyocyte growth and signaling pathways.
Main Methods:
- Activation of G(q)-coupled purinergic receptors using UTP and ATP in neonatal rat cardiomyocytes.
- Measurement of phospholipase C activation, ERK1/2, p38 MAPK, and JNK phosphorylation.
- Assessment of cardiomyocyte hypertrophic growth by measuring protein and DNA synthesis.
Main Results:
- UTP and ATP activated phospholipase C via G(q) similarly, with non-additive responses.
- Both UTP and ATP induced extracellular signal-regulated kinase (ERK1/2) phosphorylation.
- UTP (100 microM) induced hypertrophic growth (increased protein content) without DNA synthesis, while ATP (100 microM) did not increase protein content.
Conclusions:
- Activation of purinergic receptors initiates hypertrophic signaling pathways in neonatal cardiomyocytes.
- Prolonged exposure to ATP, but not UTP, exerts growth-inhibitory effects on these cells.
- Differential effects of ATP and UTP highlight distinct signaling outcomes despite shared receptor activation pathways.