Heat shock protein 60 involvement in vascular smooth muscle cell proliferation |
| |
| Institution: | 1. Institute of Cardiovascular Sciences, Albrechtsen Research Centre, St Boniface Hospital, Canada;2. Departments of Physiology and Pathophysiology, Canada;3. Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic;4. Anatomy and Cell Biology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada;1. Department of Pharmacy, Suzhou Health College, Suzhou, Jiangsu 215009, China;2. Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu 214063, China;3. Key Laboratory of Biotechnology for Analytical Medicine, Suzhou, Jiangsu 215009, China;1. Université de Lyon, Laboratoire de Biométrie et Biologie Evolutive, UMR 5558 CNRS, Université Claude Bernard Lyon 1, Villeurbanne cedex, France;2. Brain Function Research Group, School of Physiology, Faculty of Health Sciences, University of the Witwatersand, 7 York Roak, Parktown, Johannesburg 2193, South Africa;3. Université de Lyon, Laboratoire d''Ecologie des Hydrosystèmes Naturels et Anthropisés, UMR 5023 CNRS, Université Claude Bernard Lyon 1, ENTPE, Villeurbanne cedex, France;1. PHYMEDEXP, INSERM U1046, CNRS UMR9214, Université de Montpellier, CHRU Montpellier, Montpellier, France;2. EA 4278, Laboratoire de Pharm-Ecologie Cardiovasculaire, Avignon University, Avignon, France |
| |
| Abstract: | AimHeat shock protein 60 (Hsp60) is a mediator of stress-induced vascular smooth muscle cell (VSMC) proliferation. This study will determine, first, if the mitochondrial or cytoplasmic localization of Hsp60 is critical to VSMC proliferation and, second, the mechanism of Hsp60 induction of VSMC proliferation with a focus on modification of nucleocytoplasmic trafficking.Methods and resultsHsp60 was overexpressed in primary rabbit VSMCs with or without a mitochondrial targeting sequence (AdHsp60mito-). Both interventions induced an increase in VSMC PCNA expression and proliferation. The increase in VSMC PCNA expression and growth was not observed after siRNA-mediated knockdown of Hsp60 expression. Nuclear protein import in VSMC was measured by fluorescent microscopy using a microinjected fluorescent import substrate. Nuclear protein import was stimulated by both AdHsp60 and AdHsp60mito- treatments. AdHsp60 treatment also induced increases in nucleoporin (Nup) 62, Nup153, importin-α, importin-β and Ran expression as well as cellular ATP levels compared to control. AdHsp60mito- treatment induced an up-regulation in importin-α, importin-β and Ran expression compared to control. Hsp60 knockdown did not change nuclear protein import nor the expression of any nuclear transport receptors or nucleoporins. Both heat shock treatment and Hsp60 overexpression promoted the interaction of Ran with Hsp60.ConclusionsVSMC proliferation can be modulated via an Hsp60 dependent, cytosol localized mechanism that in part involves a stimulation of nuclear protein import through an interaction with Ran. This novel cellular signaling role for Hsp60 may be important in growth-based vascular pathologies like atherosclerosis and hypertension. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
