PXD045602

PXD045602 is an original dataset announced via ProteomeXchange.

Title	Mesenteric artery smooth muscle cells from hypertensive rats have increased microtubule acetylation
Description	The dynamic nature of the microtubule network is regulated in part by post-translational modifications – particularly through acetylation, which stabilizes the microtubule network. Whether post-translational modifications of the microtubule network in vascular smooth muscle cells 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), and investigate whether sustained acetylation via treatment with a histone deacetlyase-6 (HDAC-6) inhibitor, tubacin, would affect isoprenaline-mediated vasorelaxations in normotensive and hypertensive vessels.Using Western blotting, and mass spectrometry, we show that acetylation of the microtubule network is increased in the mesenteric arteries of the SHR compared to normotensive rats. Using wire myography, we found that 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 smooth muscle cells, but found no difference between control, tubacin-treated, or taxol-treated cells.Acetylation of the microtubule network is elevated in mesenteric arteries from the SHR. Furthermore, this study shows that tubacin has an endothelial-dependent bimodal effect on isoprenaline-mediated vasorelaxation. These findings pave the way for evaluation of HDAC inhibitors in the treatment of hypertension in human clinical studies.
HostingRepository	PRIDE
AnnounceDate	2024-02-21
AnnouncementXML	Submission_2024-02-21_06:45:01.905.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Anthony Mozzicato
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	acetylated residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-22 12:45:35	ID requested
⏵ 1	2024-02-21 06:45:02	announced

10.1042/BCJ20230420;

ProteomeXchange project tag: Cardiovascular (B/D-HPP), Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

submitter keyword: Hypertension, β-adrenoceptor, vasculature, PTM, Microtubules, Post-translational modification, Acetylation, Tubulin

Thomas Andrew
contact affiliation	Copenhagen University, Faculty of Health and Medicine, Biomedical Institute, Vascular Biology Group
contact email	tjepps@sund.ku.dk
lab head
Anthony Mozzicato
contact affiliation	Copenhgaen University
contact email	vrx270@alumni.ku.dk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD045602
     1. Label: PRIDE project
     2. Name: Mesenteric artery smooth muscle cells from hypertensive rats have increased microtubule acetylation