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921.
Endothelin-1 and protein kinase C co-expression in the pathogenesis of diabetic retinopathy 总被引:1,自引:0,他引:1
Wiwanitkit V 《Journal of diabetes and its complications》2007,21(6):359-362
Diabetic retinopathy (DR) is becoming one of the most important complications of diabetes at present. Endothelin-1 (ET-1) and protein kinase C (PKC) are the two important proteins involved in the pathogenesis of DR. A clarification on the interaction between ET-1 and PKC has not yet been made. Here, the author used a new gene ontology technology to predict the molecular function of ET-1 and PKC in an episode of co-expression. With the use of the GoFigure server, the molecular function of ET-1 and PKC is predicted. According to this study, different pathways can be derived from ET-1 and PKC; however, ET-1–PKC produces the same pathway as PKC. This could mean that the interaction between ET-1 and PKC results in increased activity of the PKC pathway but does not generate any new pathway. This finding can be a good explanation for the co-expression between ET-1 and PKC in the pathogenesis of DR. 相似文献
922.
Liu SY Yu XD Song CJ Lu W Zhang JD Shi XR Duan Y Zhang J 《World journal of gastroenterology : WJG》2007,13(12):1799-1804
AIM: To clone human liver special F protein and to express it in a prokaryotic system. METHODS: Total RNA was isolated from human liver tissue and first-strand cDNA was reverse transcribed using the PCR reverse primer. Following this, cDNA of the F protein was ligated into the clone vector pUCm-T. The segment of F protein's cDNA was subcloned into the expression vector pET-15b and transformed into E. coli BL21 (DE3) pLyss. Isopropy-β-D-thiogalactoside (IPTG) was then used to induce expression of the target protein. RESULTS: The cDNA clone of human liver special F protein (1134bp) was successfully produced, with the cDNA sequence being published in Gene-bank: DQ188836. We confirmed the expression of F protein by Western blot with a molecular weight of 43 kDa. The expressed protein accounted for 40% of the total protein extracted. CONCLUSION: F protein expresses cDNA clone in a prokaryotic system, which offers a relatively simple way of producing sufficient quantities of F protein and contributes to understanding the principal biological functions of this protein. 相似文献
923.
Castaman G Biguzzi E Razzari C Tosetto A Fontana G Asti D Brancaccio V Castori D Lane DA Faioni EM;for the ProSIT 《Thrombosis research》2007,120(3):421-426
A dimorphism in PROS1 gene (c.A2,001G, p.Pro667Pro) has been associated with significantly reduced levels of both free and total protein S in carriers of the GG genotype. It is not known how the GG genotype could influence PS levels in normals, whether it could influence the levels of protein S in carriers of mutations in PROS1 gene and whether this genotype acts as an isolated or additive risk factor for venous thrombosis. With this as background, we evaluated the association of p.Pro667Pro dimorphism with free and total protein S centrally measured in a panel of 119 normal controls, 222 individuals with low protein S and 137 individuals with normal PS levels belonging to 76 families with protein S deficiency enrolled in the ProSIT study. Transient expression of recombinant wild type protein S and p.Pro667Pro protein S was performed to evaluate the role of the A to G transition at position 2001 in vitro. The p.Pro667Pro polymorphism was also expressed together with a p.Glu67Ala variant to assess a possible influence on protein S levels in protein S deficient subjects. Free and total protein S levels were significantly lower in normal women. In normal women only was the GG genotype associated with significantly lower free protein S levels in comparison to AA and AG genotypes (P=0.032). No significant influence of GG genotype was observed in patients, either with known mutations or with low protein S levels. These data were confirmed by in vitro transient expression, showing no difference in secretion levels of the p.Pro667Pro variant (even in association with the p.Glu67Ala mutation), compared to the wild type protein S. The genotype in itself was neither a significant risk factor for venous thrombosis nor a risk modifier in patients with known mutations. 相似文献
924.
925.
Peroxynitrite (ONOO−)-mediated damage is regarded to be responsible for the cognitive dysfunction induced by amyloid beta protein (Aβ) in Alzheimer's disease (AD). In the present study, we examined the protective effects of rosmarinic acid (RA), a natural scavenger of ONOO−, on the memory impairment in a mouse model induced by acute i.c.v. injection of Aβ25–35. Mice daily received i.p. several doses of RA after the injection of Aβ25–35. RA prevented the memory impairments induced by Aβ25–35 in the Y maze test and novel object recognition task. RA, at the effective lowest dose (0.25 mg/kg), prevented Aβ25–35-induced nitration of proteins, an indirect indicator of ONOO− damage, in the hippocampus. At this dose, RA also prevented nitration of proteins and impairment of recognition memory induced by ONOO−-i.c.v.-injection. Co-injection of the non-memory-impairing dose of ONOO− with Aβ25–35 blocked the protective effects of RA (0.25 mg/kg). These results demonstrated that the memory protective effects of RA in the neurotoxicity of Aβ25–35 is due to its scavenging of ONOO−, and that daily consumption of RA may protect against memory impairments observed in AD. 相似文献
926.
Cazzolli R Mitchell TW Burchfield JG Pedersen DJ Turner N Biden TJ Schmitz-Peiffer C 《Diabetologia》2007,50(8):1732-1742
Aims/hypothesis Insulin resistance in skeletal muscle is strongly associated with lipid oversupply, but the intracellular metabolites and
underlying mechanisms are unclear. We therefore sought to identify the lipid intermediates through which the common unsaturated
fatty acid linoleate causes defects in IRS-1 signalling in L6 myotubes and mouse skeletal muscle.
Materials and methods Cells were pre-treated with 1 mmol/l linoleate for 24 h. Subsequent insulin-stimulated IRS-1 tyrosine phosphorylation and
its association with the p85 subunit of phosphatidylinositol 3-kinase were determined by immunoblotting. Intracellular lipid
species and protein kinase C activation were modulated by overexpression of diacylglycerol kinase ɛ, which preferentially
converts unsaturated diacylglycerol into phosphatidic acid, or by inhibition of lysophosphatidic acid acyl transferase with
lisofylline, which reduces phosphatidic acid synthesis. Phosphatidic acid species in linoleate-treated cells or muscle from
insulin-resistant mice fed a safflower oil-based high-fat diet that was rich in linoleate were analysed by mass spectrometry.
Results Linoleate pretreatment reduced IRS-1 tyrosine phosphorylation and p85 association. Overexpression of diacylglycerol kinase
ɛ reversed the activation of protein kinase C isoforms by linoleate, but paradoxically further diminished IRS-1 tyrosine phosphorylation.
Conversely, lisofylline treatment restored IRS-1 phosphorylation. Mass spectrometry indicated that the dilinoleoyl-phosphatidic
acid content increased from undetectable levels to almost 20% of total phosphatidic acid in L6 cells and to 8% of total in
the muscle of mice fed a high-fat diet. Micelles containing dilinoleoyl-phosphatidic acid specifically inhibited IRS-1 tyrosine
phosphorylation and glycogen synthesis in L6 cells.
Conclusions/interpretation These data indicate that linoleate-derived phosphatidic acid is a novel lipid species that contributes independently of protein
kinase C to IRS-1 signalling defects in muscle cells in response to lipid oversupply.
Electronic supplementary material The online version of this article (doi: ) contains supplementary material, which is available to authorised users. 相似文献
927.
Hevrøy EM El-Mowafi A Taylor RG Olsvik PA Norberg B Espe M 《General and comparative endocrinology》2007,152(1):39-46
Nutritional factors influence regulation of the growth hormone (GH) and the insulin-like growth factor (IGF) system in fish, but so far there are no published studies describing how single indispensable amino acids influence these systems. Therefore, the present study aimed to test whether lysine (Lys) intake at low (LL=2.85 g/16 gN), medium (ML=4.91 g/16 gN) and high levels (HL=9.19 g/16 gN) affected the expression of genes related to the GH-IGF system (i.e. GH receptor, GH-R, IGF-I, IGF-II, IGF binding protein 1, IGFBP-1, IGF-I receptor IGF-IR) in Atlantic salmon during seawater growth phase. Salmon fed the HL diet significantly up-regulated hepatic IGF-I mRNA level by a factor of 2.2 as compared to those with medium Lys intake. In addition a significant up-regulation of 2.7-fold in muscle IGF-II mRNA was present. Low Lys intake decreased the nitrogen deposition and muscle protein accretion in fish and significantly down-regulated hepatic IGFBP-1 as well as muscle GH-R and IGF-II, as compared to those fed the ML diet. mRNA of IGF-IR on the other hand was not affected by Lys intake. High Lys intake resulted in a 7-fold up-regulation of muscle IGF-II mRNA level as compared to low Lys intake, and thus might be an important local anabolic regulator in fast muscle tissue. The single indispensable amino acid Lys indeed affected signalling through the genes of IGF-I, IGFBP-1 in hepatic tissue and GH-R, IGF-II in fast muscle in Atlantic salmon. Concomitantly the higher Lys intake increased nitrogen deposition to a certain level. 相似文献
928.
The polyglutamine (polyQ) diseases are neurodegenerative diseases caused by proteins with an abnormally expanded polyQ stretch, which triggers abnormal aggregation of these proteins in the brain. We previously showed that the polyQ-binding peptide QBP1 inhibits polyQ aggregation, and further that administration of QBP1 fused with a protein transduction domain (PTD) suppresses polyQ-induced neurodegeneration in Drosophila. As the next step towards developing a therapy using QBP1, we investigated the delivery of PTD-QBP1 to the mouse brain upon its administration. Here we successfully detected delivery of PTD-QBP1 into mouse brain cells upon its single intracerebroventricular injection. In addition, long-term administration of PTD-QBP1 to polyQ disease mice improved their weight loss phenotype, suggesting a possible therapeutic effect. Our study indicates the potential of PTD-mediated delivery of QBP1 as a therapeutic strategy for the currently untreatable polyQ diseases. 相似文献
929.
The present study is designed to investigate the role of atypical protein kinase C (PKC) in the signaling of μ-opioid receptors (MOR) for glucose uptake in myoblast C2C12 cells. Loperamide enhanced the uptake of radioactive deoxyglucose into C2C12 cells in a concentration-dependent manner that was abolished in cells pre-incubated with GF109203X at concentrations sufficient to block PKC. Inhibition of the atypical zeta (ζ) isoform of PKC using myristoylated PKC pseudosubstrate resulted in a concentration-dependent decrease of loperamide-stimulated glucose uptake into C2C12 cells. In addition, loperamide elicited the phosphorylation of PKC-ζ in C2C12 cells in a concentration-dependent manner that was abolished by pretreatment with naloxonazine at concentrations sufficient to block MOR. These results suggest the mediation of PKC-ζ in MOR signaling for glucose uptake in C2C12 cells. Activation of PKC-ζ by MOR stimulation is highly relevant to the search for therapeutic targets for glucose transport in insulin-sensitive tissues. 相似文献
930.
Wei Boon Yap Beng Ti Tey Michelle Y.T. Ng Swee Tin Ong Wen Siang Tan 《Journal of virological methods》2009,160(1-2):125-131
The core antigen of the hepatitis B virus (HBcAg) has been used widely as a diagnostic reagent for the identification of the viral infection. However, purification using the conventional sucrose density gradient ultracentrifugation is time consuming and costly. To overcome this, HBcAg particles displaying His-tag on their surface were constructed and produced in Escherichia coli. The recombinant His-tagged HBcAgs were purified using immobilized metal affinity chromatography. Transmission electron microscopy and enzyme-linked immunosorbent assay (ELISA) revealed that the displayed His-tag did not impair the formation of the core particles and the antigenicity of HBcAg. 相似文献