Nitric oxide decreases activity and levels of the 11S proteasome activator PA28 in the vasculature.

Nitric Oxide : Biology and Chemistry
Nick D TsihlisMelina R Kibbe

Abstract

The 11S proteasome activator (PA28) binds to the 20S proteasome and increases its ability to degrade small peptides. Expression of PA28 subunits (α, β, γ) is induced by interferon-γ stimulation. Inflammation plays a role in the development of neointimal hyperplasia, and we have previously shown that nitric oxide (NO) reduces neointimal hyperplasia in animal models and 26S proteasome activity in rat aortic smooth muscle cells (RASMC). Here, we show that PA28 increased 26S proteasome activity in RASMC, as measured by a fluorogenic assay, and the NO donor S-nitroso N-acetylpenicillamine significantly inhibits this activation. This effect was abrogated by the reducing agents dithiothreitol and HgCl(2), suggesting that NO affects the activity of PA28 through S-nitrosylation. NO did not appear to affect PA28 levels or intracellular localization in RASMC in vitro. Three days following rat carotid artery balloon injury, levels of PA28α, β and γ subunits were decreased compared to uninjured control arteries (n=3/group) in vivo. The NO donor proline NONOate further decreased PA28α, β and γ levels by 1.9-, 2.3- and 3.4-fold, respectively, compared to uninjured control arteries. Fourteen days following arterial injury, levels of PA28α, β a...Continue Reading

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Citations

Feb 11, 2014·Antioxidants & Redox Signaling·Nicola Wilck, Antje Ludwig
Feb 20, 2016·Journal of Experimental & Clinical Cancer Research : CR·Xiaodong FengQianming Chen
Jun 14, 2014·Arteriosclerosis, Thrombosis, and Vascular Biology·Begoña LavinCarlos Zaragoza

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