Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In tobacco cells, osmotic stress induced the rapid activation of two protein kinases that phosphorylate myelin basic protein. Immunological studies demonstrated that the 48-kD kinase is the salicylic acid-induced protein kinase (SIPK), a member of the mitogen-activated protein kinase family. SIPK was activated 5 to 10 min after the cells were exposed to osmotic stresses, and its activity persisted for approximately 30 min. In contrast, the 42-kD kinase was activated within 1 min after osmotic stress, and its activity was maintained for approximately 2 hr. Moreover, in addition to myelin basic protein, the 42-kD kinase phosphorylated casein and two transcription factors, c-Jun and ATF-2. This latter enzyme was inactivated by a serine/threonine-specific phosphatase but, unlike SIPK, was not affected by a tyrosine-specific phosphatase. After the 42-kD kinase was purified to apparent homogeneity, tryptic peptide analysis indicated that it is a homolog of Arabidopsis serine/threonine kinase1 (ASK1).
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PMID:Osmotic stress induces rapid activation of a salicylic acid-induced protein kinase and a homolog of protein kinase ASK1 in tobacco cells. 1063 15

Recently, we observed that 8-hydroxyguanosine triphosphate and 8-hydroxy-2'-deoxyguanosine (oh(8)dG) inactivate Rac and consequently down-regulate the Rac-linked NADPH oxidase, iNOS, and Cox2. Based on these observations, we tested whether oh(8)dG has anti-inflammatory activity in vivo in lipopolysaccharide (LPS)-treated mice. LPS (1 mg/kg, ip)-treated mice exhibit marked inflammatory responses, including increases in proinflammatory cytokines (TNF-alpha, IL-6, IL-18, and IL-12p70) in serum and infiltration of neutrophils, increased translocation of NF-kappaB p50 from the cytosol to the nucleus, and phosphorylation of c-Jun in lung tissues. Mice were pretreated with oh(8)dG (up to 60 mg/kg, ip) 4 h before LPS injection, and this pretreatment dose-dependently inhibited the inflammatory responses; the inhibitions observed with 60 mg/kg oh(8)dG were statistically significant. At the same time, oh(8)dG pretreatment inactivated Rac in lung tissues. Oh(8)dG pretreatment (50 mg/kg, ip) also significantly protected against LPS-induced septic death. Furthermore, oh(8)dG was more effective than acetyl salicylic acid in inhibiting these inflammatory responses. 8-Hydroxyguanosine also had some effect but was much weaker than oh(8)dG. The effects of normal nucleosides (dG, G, and A) were negligible or not significant. These results support an anti-inflammatory activity for oh(8)dG, which could be ascribed to its Rac-inactivating action.
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PMID:Anti-inflammatory effects of 8-hydroxy-2'-deoxyguanosine on lipopolysaccharide-induced inflammation via Rac suppression in Balb/c mice. 1803 25

NCX 4016 is a nitric oxide (NO)-donating derivative of acetylsalicylic acid. NO and salicylate, in vivo metabolites of NCX 4016, were shown to be potential actors in controlling glucose homeostasis. In this study, we evaluated the action of NCX 4016 on the capacity of 3T3-L1 adipocytes to transport glucose in basal and insulin-stimulated conditions. NCX 4016 induced a twofold increase in glucose uptake in parallel with the translocation of the glucose transporters GLUT1 and GLUT4 to the plasma membrane, leaving unaffected their total expression levels. Importantly, NCX 4016 further increased glucose transport induced by a physiological concentration of insulin. The stimulatory effect of NCX 4016 on glucose uptake appears to be mediated by its NO moiety. Indeed, it is inhibited by a NO scavenger and treatment with acetylsalicylic or salicylic acid had no effect. Although NO is involved in the action of NCX 4016, it did not mainly depend on the soluble cGMP cyclase/protein kinase G pathway. Furthermore, NCX 4016-stimulated glucose transport did not involve the insulin-signaling cascade required to stimulate glucose transport. NCX 4016 induces a small activation of the mitogen-activated protein kinases p38 and c-Jun NH(2)-terminal kinase and no activation of other stress-activated signaling molecules, including extracellular signal-regulated kinase, inhibitory factor kappaB, or AMP-activated kinases. Interestingly, NCX 4016 modified the content of S-nitrosylated proteins in adipocytes. Taken together, our results indicate that NCX 4016 induced glucose transport in adipocytes through a novel mechanism possibly involving S-nitrosylation. NCX 4016 thus possesses interesting characteristics to be considered as a candidate molecule for the treatment of patients suffering from metabolic syndrome and type 2 diabetes.
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PMID:The nitric oxide-donating derivative of acetylsalicylic acid, NCX 4016, stimulates glucose transport and glucose transporters translocation in 3T3-L1 adipocytes. 1849 71