Mesenteric artery smooth muscle cells from hypertensive rats have increased microtubule acetylation.

Autor:	Mozzicato AM; Vascular Biology Group, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark., Bastrup JA; Vascular Biology Group, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark., Sanchez-Alonso JL; Myocardial Function, National Heart and Lung Institute, Imperial College London, ICTEM, Hammersmith Hospital, London, U.K., van der Horst J; Vascular Biology Group, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark., Gorelik J; Myocardial Function, National Heart and Lung Institute, Imperial College London, ICTEM, Hammersmith Hospital, London, U.K., Hägglund P; Protein Oxidation Group, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark., Jepps TA; Vascular Biology Group, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jazyk:	angličtina
Zdroj:	The Biochemical journal [Biochem J] 2024 Mar 06; Vol. 481 (5), pp. 387-403.
DOI:	10.1042/BCJ20230420
Abstrakt:	The dynamic nature of the microtubule network is dependent in part by post-translational modifications (PTMs) - particularly through acetylation, which stabilizes the microtubule network. Whether PTMs of the microtubule network in vascular smooth muscle cells (VSMCs) contribute to the pathophysiology of hypertension is unknown. The aim of this study was to determine the acetylated state of the microtubule network in the mesenteric arteries of spontaneously hypertensive rats (SHR). Experiments were performed on male normotensive rats and SHR mesenteric arteries. Western blotting and mass spectrometry determined changes in tubulin acetylation. Wire myography was used to investigate the effect of tubacin on isoprenaline-mediated vasorelaxations. Isolated cells from normotensive rats were used for scanning ion conductance microscopy (SICM). Mass spectrometry and Western blotting showed that tubulin acetylation is increased in the mesenteric arteries of the SHR compared with normotensive rats. Tubacin enhanced the β-adrenoceptor-mediated vasodilatation by isoprenaline when the endothelium was intact, but attenuated relaxations when the endothelium was denuded or nitric oxide production was inhibited. By pre-treating vessels with colchicine to disrupt the microtubule network, we were able to confirm that the effects of tubacin were microtubule-dependent. Using SICM, we examined the cell surface Young's modulus of VSMCs, but found no difference in control, tubacin-treated, or taxol-treated cells. Acetylation of tubulin at Lys40 is elevated in mesenteric arteries from the SHR. Furthermore, this study shows that tubacin has an endothelial-dependent bimodal effect on isoprenaline-mediated vasorelaxation. (© 2024 The Author(s).)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu