Calponin 1 inhibits agonist-induced ERK activation and decreases calcium sensitization in vascular smooth muscle.

Autor: Kajuluri LP; Vascular Biology Laboratory, Department of Health Sciences, Boston University, Boston, Massachusetts, USA., Lyu QR; Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, Georgia, USA.; Medical Research Center, Chongqing General Hospital, Chongqing, China., Doja J; Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, Georgia, USA., Kumar A; Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, Georgia, USA., Wilson MP; University of Rochester Medical Center, Rochester, New York, USA., Sgrizzi SR; Vascular Biology Laboratory, Department of Health Sciences, Boston University, Boston, Massachusetts, USA., Rezaeimanesh E; Vascular Biology Laboratory, Department of Health Sciences, Boston University, Boston, Massachusetts, USA., Miano JM; Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, Georgia, USA., Morgan KG; Vascular Biology Laboratory, Department of Health Sciences, Boston University, Boston, Massachusetts, USA.
Jazyk: angličtina
Zdroj: Journal of cellular and molecular medicine [J Cell Mol Med] 2024 Jan; Vol. 28 (1), pp. e18025. Date of Electronic Publication: 2023 Dec 26.
DOI: 10.1111/jcmm.18025
Abstrakt: Smooth muscle cell (SMC) contraction and vascular tone are modulated by phosphorylation and multiple modifications of the thick filament, and thin filament regulation of SMC contraction has been reported to involve extracellular regulated kinase (ERK). Previous studies in ferrets suggest that the actin-binding protein, calponin 1 (CNN1), acts as a scaffold linking protein kinase C (PKC), Raf, MEK and ERK, promoting PKC-dependent ERK activation. To gain further insight into this function of CNN1 in ERK activation and the regulation of SMC contractility in mice, we generated a novel Calponin 1 knockout mouse (Cnn1 KO) by a single base substitution in an intronic CArG box that preferentially abolishes expression of CNN1 in vascular SMCs. Using this new Cnn1 KO mouse, we show that ablation of CNN1 has two effects, depending on the cytosolic free calcium level: (1) in the presence of elevated intracellular calcium caused by agonist stimulation, Cnn1 KO mice display a reduced amplitude of stress and stiffness but an increase in agonist-induced ERK activation; and (2) during intracellular calcium depletion, in the presence of an agonist, Cnn1 KO mice exhibit increased duration of SM tone maintenance. Together, these results suggest that CNN1 plays an important and complex modulatory role in SMC contractile tone amplitude and maintenance.
(© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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