Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.24 (mitogen-activated protein kinase)
 95,810 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this study was to investigate the chemopreventive potentials of glycine- and proline-rich glycoprotein (SNL glycoprotein, 150-kDa) isolated from Solanum nigrum Linne on formation of colonic aberrant crypt foci (ACF) induced by 1,2-dimethylhydrazine (DMH, 20 mg/kg) in A/J mice. Administration of SNL glycoprotein inhibited phosphorylation of extracellular signal-regulated kinase (ERK), expression of colonic proliferating cell nuclear antigen (PCNA), and frequency of colonic ACF in DMH-stimulated mice colon carcinogenesis. In addition, SNL glycoprotein increased expression of cyclin-dependent kinase inhibitors (p21(WAF/Cip1) and p27(Kip1)), whereas reduced expression of precursor form of apoptosis-related proteins [pro-caspase-3 and pro-poly(ADP-ribose)polymerase (PARP)] in the mice. Interestingly, the results in this study revealed that SNL glycoprotein has suppressive effects on activity of nuclear factor-kappa B (NF-kappaB), whereas it has stimulatory effect on the expression of p53, accompanying inhibitory effects on expression of NF-kappaBp50, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha in DMH-stimulated ACF formation. Also, SNL glycoprotein has inhibitory effects on the formation of thiobarbituric acid reactive substances (TBARS), on the production of inducible nitric oxide (NO), and on the release of lactate dehydrogenase (LDH) in the mice plasma. Collectively, our findings in this study suggest that SNL glycoprotein has chemopreventive activity via modulation of cell proliferation and apoptosis in DMH-treated A/J mice.
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PMID:Glycine- and proline-rich glycoprotein regulates the balance between cell proliferation and apoptosis for ACF formation in 1,2-dimethylhydrazine-treated A/J mice. 1918 65

Oxidative stress and dysfunctional mitochondria are among the earliest events in AD, triggering neurodegeneration. The use of natural antioxidants could be a neuroprotective strategy for blocking cell death. Here, the antioxidant action of ferulic acid (FA) on different paths leading to degeneration of recombinant beta-amyloid peptide (rAbeta42) treated cells was investigated. Further, to improve its delivery, a novel drug delivery system (DDS) was used. Solid lipid nanoparticles (SLNs), empty or containing ferulic acid (FA-SNL), were developed as DDS. The resulting particles had small colloidal size and highly negative surface charge in water. Using neuroblastoma cells and rAbeta42 oligomers, it was demonstrated that free and SLNs-loaded FA recover cell viability. FA treatment, in particular if loaded into SLNs, decreased ROS generation, restored mitochondrial membrane potential (Deltapsi(m)) and reduced cytochrome c release and intrinsic pathway apoptosis activation. Further, FA modulated the expression of Peroxiredoxin, an anti-oxidative protein, and attenuated phosphorylation of ERK1/2 activated by Abeta oligomers.
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PMID:Ferulic acid inhibits oxidative stress and cell death induced by Ab oligomers: improved delivery by solid lipid nanoparticles. 1986 73

A differential role of endothelin-1 (ET-1) in pain processing has recently been suggested. However, the function of central ET-1 in neuropathic pain (NP) has not been fully elucidated to date. We report here the action of endogenous central ET-1 in sciatic nerve ligation-induced NP (SNL-NP) in a transgenic animal model that over-expresses ET-1 in the astrocytes (GET-1 mice). We hypothesized that the over-expression of astrocytic ET-1 would exert anti-allodynic and anti-hyperalgesic effects in NP, as demonstrated by mechanical threshold and plantar withdrawal latency using the von Frey filament and heat stimuli. In our animal model, GET-1 mice showed an increase in the withdrawal threshold and latency in response to the mechanical and thermal stimuli, respectively, in pain behavior tests after SNL. ET-1 and endothelin type A receptor (ETA-R) levels were increased significantly in L4-L6 segments of the spinal cord (ipsilateral to SNL) of GET-1 mice at 7 and 21days after surgery. Moreover, intrathecal administration of a specific ETA-R antagonist, BQ-123, attenuated the anti-allodynic and anti-hyperalgesic phenotype in GET-1 mice. The effects of BQ-123 on the mRNA expression of extracellular signal-regulated protein kinase 1/2 (ERK1/2) and protein kinase B/serine protein kinase (Akt(s)) were assessed in the ipsilateral L4-L6 segments harvested 30min after BQ-123 administration on day 7 after surgery. Phosphorylation of ERK1/2 and Akt(s) in the ipsilateral spinal cord of GET-1 mice was reduced following SNL, whereas no reduction was observed after intrathecal injection of BQ-123. In conclusion, our results showed that the xover-expression of astrocytic ET-1 reduced SNL-induced allodynia and hyperalgesia by inhibiting the activation of ERK1/2 and Akt(s) via the ETA-R-mediated pathway.
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PMID:Over-expression of astrocytic ET-1 attenuates neuropathic pain by inhibition of ERK1/2 and Akt(s) via activation of ETA receptor. 2459 54