Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

Trans-cellular proliferating cell nuclear antigen gene activation in cerebral vascular smooth muscle by endothelial oxidative injury in vivo.

Gerzanich V., Ivanova S., van der Heijden M.S., Zhou H., Simard J.M.

This study was undertaken to assess the role of vascular smooth muscle cell (VSMC) Ca2+ channels and Ca2+/calmodulin-dependent protein kinase II (CaMKII) in gene regulation after oxidative endothelial injury (OEI).OEI was produced by infusion of Na fluorescein (NaFluo) photoactivated by UV light immediately before intravenous injection. Posterior cerebral arteries were studied using immunofluorescence imaging, Western blotting, or patch clamping of isolated cells. After infusion of photoactivated NaFluo, but not NaFluo, (1) superoxide dismutase-1 (SOD-1) was upregulated in endothelium, consistent with oxidant stress; (2) the fraction of VSMC nuclei labeled for proliferating cell nuclear antigen (PCNA) increased 7-fold at 6 hours, preceded by a several-fold increase in nuclear phospho-cAMP-response element binding protein, with PCNA upregulation prevented by pretreatment with polyethylene glycol (PEG)-SOD; (3) in VSMCs, phospho-CaMKII increased 20-fold 5 minutes after OEI, with a 2-fold increase in peak Ca2+ channel currents; and (4) changes in cAMP-response element binding protein and PCNA were blocked by systemic administration of lipophilic (nifedipine) or hydrophilic (amlodipine) 1,4-dihydropyridine Ca2+ channel blockers, the calmodulin inhibitor trifluoperazine, or the CaMKII inhibitor KN-93, with none of these agents preventing SOD-1 upregulation in endothelium.Activation of VSMC Ca2+ channels and CaMKII is a key early signaling event required for upregulation of PCNA gene expression in VSMCs after oxidative injury to endothelium.

Arterioscler. Thromb. Vasc. Biol. 23:2048-2054(2003) [PubMed] [Europe PMC]

UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again