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Transforming growth factor beta-1 attenuates endothelin-1-induced functions in neonatal cardiac myocytes
John A Johnson1, Jennifer Waller
1The Department of Pharmacology and Toxicology, School of Medicine, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912-2300, USA. jjohnson@mail.mcg.edu
Abstract:
In the present study we characterized a "crosstalk" mechanism between transforming growth factor beta-1 (TGF beta-1) and endothelin-1 (ET1) signaling pathways in neonatal cardiac myocytes. A 5 minute pretreatment with 1 ng/ml concentrations of TGF beta-1 attenuated ET1-induced negative chronotropic effects and translocation of the alpha, delta and varepsilonPKC isozymes to the particulate cell fraction. We found no effect of TGF beta-1 on responses induced by the P(2) purinergic agonist ATP or phorbol ester. Treatment of cardiac myocytes with acidic fibroblast growth factor (aFGF) did not alter ET1- or ATP-mediated effects on contraction rate or translocation of PKC isozymes to the particulate fraction. Our studies suggest that TGF beta-1 may act as a negative modulator of ET1- but not ATP- or phorbol ester-induced PKC isozyme signaling events in neonatal cardiac myocytes. A better understanding of the complex ET1 and TGF beta-1 signaling mechanisms in neonatal heart cells should enhance our knowledge regarding the interplay between these pathways.
Insights
Transforming growth factor beta-1 (TGF beta-1) negatively modulates endothelin-1 (ET1) signaling in neonatal heart cells. This crosstalk affects protein kinase C (PKC) isozyme translocation, impacting cardiac myocyte function.
Area of Science:
- Cardiology
- Molecular Biology
- Cell Signaling
Background:
- Neonatal cardiac myocytes exhibit complex signaling pathways.
- Transforming growth factor beta-1 (TGF beta-1) and endothelin-1 (ET1) are key regulators of cardiac function.
- Understanding crosstalk between these pathways is crucial for cardiac health.
Purpose of the Study:
- To characterize the crosstalk mechanism between TGF beta-1 and ET1 signaling in neonatal cardiac myocytes.
- To investigate the impact of TGF beta-1 on ET1-induced cellular responses.
- To determine the role of protein kinase C (PKC) isozymes in this interaction.
Main Methods:
- Neonatal cardiac myocytes were pretreated with TGF beta-1.
- ET1-induced effects on chronotropic function and PKC isozyme translocation were measured.
- Responses to ATP and phorbol ester were assessed for comparison.
- Acidic fibroblast growth factor (aFGF) was used as a control.
Main Results:
- TGF beta-1 pretreatment attenuated ET1-induced negative chronotropic effects.
- TGF beta-1 inhibited ET1-mediated translocation of alpha, delta, and epsilonPKC isozymes.
- TGF beta-1 had no effect on responses to ATP or phorbol ester.
- aFGF did not alter ET1- or ATP-mediated effects.
Conclusions:
- TGF beta-1 acts as a negative modulator of ET1 signaling in neonatal cardiac myocytes.
- This modulation specifically involves PKC isozyme signaling pathways.
- Further research into ET1 and TGF beta-1 interplay is warranted for neonatal heart cell knowledge.