Johnson John A, Waller Jennifer
The Department of Pharmacology and Toxicology, School of Medicine, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912-2300, USA.
Life Sci. 2002 May 24;71(1):99-113. doi: 10.1016/s0024-3205(02)01624-7.
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.
在本研究中，我们阐述了新生心肌细胞中转化生长因子β-1（TGFβ-1）与内皮素-1（ET1）信号通路之间的“串扰”机制。用1 ng/ml浓度的TGFβ-1进行5分钟预处理，可减弱ET1诱导的负性变时效应以及α、δ和ε蛋白激酶C（PKC）同工酶向颗粒细胞组分的转位。我们发现TGFβ-1对P2嘌呤能激动剂ATP或佛波酯诱导的反应没有影响。用酸性成纤维细胞生长因子（aFGF）处理心肌细胞，不会改变ET1或ATP介导的对收缩速率的影响，也不会改变PKC同工酶向颗粒组分的转位。我们的研究表明，TGFβ-1可能作为ET1诱导的PKC同工酶信号事件的负性调节因子，但不是ATP或佛波酯诱导的PKC同工酶信号事件的负性调节因子。更好地理解新生心脏细胞中复杂的ET1和TGFβ-1信号机制，应能增进我们对这些通路之间相互作用的认识。
