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Nitric oxide (NO) inhibits vascular inflammation, but the molecular basis for its anti-inflammatory properties is unknown. We show that NO inhibits exocytosis of Weibel-Palade bodies, endothelial granules that mediate vascular inflammation and thrombosis, by regulating the activity of N-ethylmaleimide-sensitive factor (NSF). NO inhibits NSF disassembly of(More)
The mitogen-activated protein kinase (MAPK) pathway plays a critical role in Toll-like receptor (TLR) signaling. MAPK phosphatase-1 (MKP-1) inhibits the MAPK pathway and decreases TLR signaling, but the regulation of MKP-1 is not completely understood. We now show that MKP-1 is acetylated, and that acetylation regulates its ability to interact with its(More)
Intracerebral hemorrhage (ICH) is a devastating form of stroke. Misoprostol, a synthetic prostaglandin E1 (PGE1) analog and PGE2 receptor agonist, has shown protection against cerebral ischemia. In this study, we tested the efficacy of misoprostol in the 12-month-old mice subjected to 1 of 2 complementary ICH models, the collagenase model (primary study)(More)
Cerebellar ataxias, which comprise a wide spectrum of progressive disorders, are incurable at present. It has been reported that human umbilical mesenchymal stem cell (HU-MSC) transplantation has a protective effect on neurodegenerative diseases. In this study, we investigated the effect of HU-MSCs on ataxic mice induced by cytosine beta-D-arabinofuranoside(More)
Transforming growth factor-beta (TGF-beta) increases expression of endothelial nitric oxide synthase (eNOS), although the precise mechanism by which it does so is unclear. We report that Smad2, a transcription factor activated by TGF-beta, mediates TGF-beta induction of eNOS in endothelial cells. TGF-beta induces Smad2 translocation from cytoplasm to(More)
BACKGROUND AND PURPOSE Carbon monoxide (CO) is a gaseous second messenger produced when heme oxygenase enzymes catabolize heme. We have demonstrated that CO can be therapeutic in ischemia-reperfusion brain injury; however, it is unclear whether CO can also offer protection in permanent ischemic stroke or what mechanism(s) underlies the effect. Heme(More)
Interest in histone deacetylase (HDAC)-based therapeutics as a potential treatment for stroke has grown dramatically. The neuroprotection of HDAC inhibition may involve multiple mechanisms, including modulation of transcription factor acetylation independent of histones. The transcription factor Nrf2 has been shown to be protective in stroke as a key(More)
TIMAP is a prenylated endothelial cell protein with a domain structure that predicts it to be a protein phosphatase-1 (PP-1) regulatory subunit. We found that TIMAP interacts with the 37/67 kDa laminin receptor (LAMR1) in yeast two-hybrid assays. In endothelial cells, endogenous TIMAP and LAMR1 co-immunoprecipitated and co-localized at the plasma membrane.(More)
INTRODUCTION Osteoarthritis (OA) is a common joint disease that can cause gradual disability among the aging population. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a key transcription factor that regulates the expression of phase II antioxidant enzymes that provide protection against oxidative stress and tissue damage. The use of histone(More)
Cerebral deposition of amyloid-beta peptide (Abeta) is a critical feature of Alzheimer's disease (AD). Either aluminium trichloride (Al) or D-galactose (D-gal) induces Abeta overproduction in rat or mouse brain and has been used to produce models of aging and AD. Here it is shown that mice treated with Al plus D-gal represent a good model of AD with altered(More)