Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to determine whether nuclear factor-kappaB (NF-kappaB) inhibitors are efficient against hepatic ischemia/reperfusion (I/R) injury. We previously demonstrated that xanthine oxidase-derived reactive oxygen species activate NF-kappaB during ischemia. However, the role of NF-kappaB activation during ischemia in post-reperfusion injury remains unclear. Therefore, while we examined the effects of NF-kappaB inhibitors, sulfasalazine and pyrrolidinedithiocarbamate on hepatic I/R injury using a rat lobar hepatic I/R model, we estimated the relationship between NF-kappaB activation during ischemia and following hepatic damage caused by reperfusion. The portal vein and the hepatic artery were clamped for 1 hr followed by reperfusion for up to 24 hr. NF-kappaB activation was determined by Western blot analysis. NF-kappaB activation was observed in the ischemic lobe of the liver, and the activation was prevented by pre-administration with NF-kappaB inhibitors. Although the serum ALT level, hepatic MPO activity and BSP clearance, as an index of hepatic injury, were increased after reperfusion, the increase was attenuated by pre-administration with NF-kappaB inhibitors. These findings suggest that NF-kappaB activation during ischemia is relevant to hepatic I/R injury. Moreover, we first showed that pre-administration with NF-kappaB inhibitors is effective against hepatic I/R injury.
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PMID:Inhibiton of NF-kappaB activation during ischemia reduces hepatic ischemia/reperfusion injury in rats. 1592 58

Oxidative stress may play a major role in age-related osteoporosis in part by inhibiting osteoblast generation from osteoprogenitors cells. In the present study, we hypothesized that oxidative stress may inhibit the osteogenic differentiation of bone marrow stromal cells (MSC) in part by inhibiting the Hedgehog (Hh) signaling pathway, which is essential for bone development and maintenance and induces osteogenic differentiation of osteoprogenitor cells. To test this hypothesis, we examined the effects of oxidative stress on Sonic Hh (Shh)-induced osteogenic differentiation and signaling in M2-10B4 (M2) MSC, C3H10T1/2 embryonic fibroblasts, and mouse primary MSC. Treatment of cells with H(2)O(2) inhibited Shh-induced osteogenic differentiation determined by the inhibition of Shh-induced expression of osteogenic differentiation markers alkaline phosphatase (ALP), osterix (OSX), and bone sialoprotein (BSP). Similar effects were found when oxidative stress was induced by xanthine/xanthine oxidase (XXO) or minimally oxidized LDL (MM-LDL). H(2)O(2) , XXO, and MM-LDL treatment inhibited Shh-induced expression of the Hh target genes Gli1 and Patched1 as well as Gli-dependent transcriptional activity in M2 cells. H(2)O(2) treatment also inhibited Hh signaling induced by the direct activation of Smoothened by purmorphamine (PM), but not by Gli1 overexpression. This suggests that oxidative stress may inhibit Hh signaling upstream of Gli activation and Gli-induced gene expression. These findings demonstrate for the first time that oxidative stress inhibits Hh signaling associated with osteogenic differentiation. Inhibition of Hh signaling-mediated osteogenic differentiation of osteoprogenitor cells may in part explain the inhibitory effects of oxidative stress on osteoblast development, differentiation, and maintenance in aging.
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PMID:Hedgehog signaling and osteogenic differentiation in multipotent bone marrow stromal cells are inhibited by oxidative stress. 2071 24