Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To analyze gene expression in oral cancer, we produced a specialized in-house cDNA microarray. The cDNA library was constructed from surgical specimens of oral squamous cell carcinoma (SCC) using an oligo-capping method. cDNA clones (n=4,800) were randomly selected and their 5'-end nucleotide sequences were determined. Overlapping clones were excluded, and 1,423 independent clones were selected and used for microarray production. Compared to the public nucleotide sequence database, 61% of our cDNA clones were full-length. By correlating expression patterns across SCC cell lines, we identified 53 genes (7 up-regulated and 46 down-regulated) that are differentially expressed in SCC cell lines compared to normal mucosa. Semi-quantitative RT-PCR analysis confirmed these findings and validity of our cDNA microarray. Using specimens from SCC patients, we investigated the expression status of the IL-1ra gene, which showed the down-regulated gene by microarray analysis. Gene expression clearly fell in the SCC specimens relative to their references, which indicated that our in-house cDNA microarray system rapidly identified and characterized candidate biomarkers for clinical use.
Int J Mol Med 2003 Oct
PMID:In-house cDNA microarray analysis of gene expression profiles involved in SCC cell lines. 1296 14

Retrotransposons are major, dispersed components of most eukaryotic genomes. They replicate by a cycle of transcription, reverse transcription, and integration of new copies, without excising from the genome in the process. Because they represent a major share of the genome, cause easily detectable genetic changes having known ancestral and derived states, and contain conserved regions for which polymerase chain reaction (PCR) primers may be designed, retrotransposon insertions can be exploited as powerful molecular marker systems. Here, we describe the background and strategies, as well as give detailed laboratory protocols, for four key retrotransposon-based methods: SSAP, IRAP, REMAP, and RBIP. The SSAP, IRAP, and REMAP methods are multiplex and generate anonymous marker bands; RBIP scores individual loci, much as microsatellite-based marker systems do. The methods are variously suited to marker detection on agarose and polyacrylamide slab gels, slab and capillary sequencing devices, and arrays on solid supports. The different strengths and weaknesses of these approaches and their performance relative to conventional marker methods are discussed, together with their applicability to marker-assisted breeding, phylogenetic analyses, biodiversity determinations, and evolutionary studies.
Methods Mol Biol 2004
PMID:The application of LTR retrotransposons as molecular markers in plants. 1502 Aug 8

We have shown that the sera of lung cancer patients affect the response of ConA-stimulated normal peripheral blood mononuclear cells by decreasing the expression of IL-2Ralpha and inhibiting the release of IL-1beta and IL-2. A tendency to enhance the release of IL-6 was also observed. We conclude that an imbalance in the Th1/Th2 cytokine response, typical for cancer patients, may at least partly be related to soluble factors circulating in the patients' blood. We discuss a putative role of serum IL-10, IL-1ra, and soluble IL-2Ralpha in the effects observed.
Cell Mol Biol Lett 2004
PMID:Sera of lung cancer patients affect the release of Th1, Th2 and monocyte-derived cytokines, and the expression of IL-2Ralpha by normal, stimulated mononuclear cells. 1504 52

Two families of transcription factors that play a major role in the development of adipocytes are the CCAAT/enhancer-binding proteins (C/EBPs) and the peroxisome proliferator-activated receptors (PPARs), in particular PPAR gamma. Ectopic expression of either C/EBP alpha or PPAR gamma in NIH 3T3 fibroblasts results in the conversion of these cells to adipocyte-like cells replete with fat droplets. NIH 3T3 cells ectopically expressing C/EBP alpha (NIH-C/EBP alpha) differentiate into adipocytes and exhibit insulin-stimulated glucose uptake, whereas NIH 3T3 cells ectopically expressing PPAR gamma (NIH-PPAR gamma) differentiate but do not exhibit any insulin-stimulated glucose uptake, nor do they express any C/EBP alpha. The reason for the lack of insulin-responsive glucose uptake in the NIH-PPAR gamma cells is their virtual lack of the insulin-responsive glucose transporter, Glut4. The NIH-PPAR gamma cells express functionally active components of the insulin receptor-signaling pathway (the insulin receptor, IRS-1, phosphatidylinositol 3-kinase, and Akt2) at levels comparable to those in responsive cell lines. They also express components of the insulin-sensitive vesicular transport machinery, namely, VAMP2, syntaxin-4, and IRAP, the last of these being the other marker of insulin-regulated vesicular traffic along with Glut4. Interestingly, the NIH-PPAR gamma cells show normal insulin-dependent translocation of IRAP and form an insulin-responsive vesicular compartment as assessed by cell surface biotinylation and sucrose velocity gradient analysis, respectively. Moreover, expression of a Glut4-myc construct in the NIH-PPAR gamma cells results in its insulin-dependent translocation to the plasma membrane as assessed by immunofluorescence and Western blot analysis. Based on these data, we conclude that major role of C/EBP alpha in the context of the NIH-PPAR gamma cells is to regulate Glut4 expression. The differentiated cells possess a large insulin-sensitive vesicular compartment with negligible Glut4, and Glut4 translocation can be reconstituted on expression of this transporter.
Mol Cell Biol 2004 Aug
PMID:Glut4 storage vesicles without Glut4: transcriptional regulation of insulin-dependent vesicular traffic. 1528 14

GLUT4 (glucose transporter 4) plays a pivotal role in insulin-induced glucose uptake to maintain normal blood glucose levels. Here, we report that a cell-permeable phosphoinositide-binding peptide induced GLUT4 translocation to the plasma membrane without inhibiting IRAP (insulin-responsive aminopeptidase) endocytosis. However, unlike insulin treatment, the peptide treatment did not increase glucose uptake in 3T3-L1 adipocytes, indicating that GLUT4 translocation and activation are separate events. GLUT4 activation can occur at the plasma membrane, since insulin was able to increase glucose uptake with a shorter time lag when inactive GLUT4 was first translocated to the plasma membrane by pretreating the cells with this peptide. Inhibition of phosphatidylinositol (PI) 3-kinase activity failed to inhibit GLUT4 translocation by the peptide but did inhibit glucose uptake when insulin was added following peptide treatment. Insulin, but not the peptide, stimulated GLUT1 translocation. Surprisingly, the peptide pretreatment inhibited insulin-induced GLUT1 translocation, suggesting that the peptide treatment has both a stimulatory effect on GLUT4 translocation and an inhibitory effect on insulin-induced GLUT1 translocation. These results suggest that GLUT4 requires translocation to the plasma membrane, as well as activation at the plasma membrane, to initiate glucose uptake, and both of these steps normally require PI 3-kinase activation.
Mol Cell Biol 2004 Sep
PMID:Separation of insulin signaling into distinct GLUT4 translocation and activation steps. 1531 66

It has been reported that apelin functions as an adipokine, which has been associated to obesity and insulin resistance. The objective of this study was to analyze the apelin mRNA expression in white adipose tissue (WAT) from high-fat (Cafeteria) fed rats, in order to examine potential relationships with obesity markers and other related risk factors. Animals fed on the high-fat diet during 56 days increased their body weight, total body fat and WAT depots weights when compared to controls. Apelin subcutaneous mRNA expression was higher in the Cafeteria than in the Control fed group and this increase was partially reversed by dietary vitamin C supplementation. Statistically significant associations between subcutaneous apelin gene expression and almost all the studied variables were identified, being of special interest the correlations found with serum leptin (r=0.517), liver malondialdehyde (MDA) levels (r=0.477), and leptin, IRS-3 and IL-1ra retroperitoneal mRNA expression (r=0.701; r=0.692 and r=0.561, respectively). These associations evidence a possible role for apelin in the excessive weight gain induced by high-fat feeding and increased adiposity, insulin-resistance, liver oxidative stress and inflammation.
Mol Cell Biochem 2007 Nov
PMID:Adiposity dependent apelin gene expression: relationships with oxidative and inflammation markers. 1759 60

Neural precursor cells (NPCs) have been experimentally used to repair the damaged nervous system either by exogenous transplantation or by endogenous activation. In post-injury inflammation, an array of cytokines including interleukin-1beta (IL-1beta) are released by host as well as invading immune cells and increased markedly. In the present study, we investigated the effects of IL-1beta on the survival, proliferation, differentiation and migration of NPCs as well as underlying intracellular signaling pathways. NPCs derived from the E16 rat brain were expanded in neurospheres that were found to express IL-1beta, IL-1RI and IL-1RII, but not IL-1alpha and IL-1ra. IL-1beta inhibited the proliferation of NPCs in a dose-dependent manner, an effect that can be reversed by IL-1ra, an antagonist for IL-1 receptor. This inhibitory effect of IL-1beta on NPCs proliferation resulted in part from its effect on increased apoptosis of NPCs. Moreover, IL-1ra did not affect NPCs lineage fate but rather inhibited GFAP expression in differentiated astrocytes. We also found that IL-1ra had no effect on the transmigration of NPCs in vitro. Finally, we showed that the effect of IL-1beta on NPCs proliferation and differentiation appeared to be mediated by SAPK/JNK, but not ERK, P38MAPK nor NF-kappaB pathways. These findings collectively suggest that the inflammatory environment following CNS injuries may influence the ability of NPCs to repair the damage.
Mol Cell Neurosci 2007 Nov
PMID:Interleukin-1beta mediates proliferation and differentiation of multipotent neural precursor cells through the activation of SAPK/JNK pathway. 1782 21

Interleukin-1 (IL-1) is a potent regulator of cell proliferation, inflammation, and contraction of cardiovascular cells. It has been proposed that the IL-1/IL-1ra (IL-1 receptor antagonist) ratio influences these functions. Other members of the IL-1 family and the related caspase-1 also contribute to regulation of IL-1-mediated functions. We determined the mRNA expression of caspase-1, caspase-3, IL-1alpha , IL-1beta , IL-18, IL-1 receptor type I (IL-1-RI), and IL-1ra in left ventricle tissue of hearts from patients with ischemic or dilated cardiomyopathy (ICM or DCM) and in control tissues from unused donor transplant hearts in RT-PCR experiments. We show that the expression of caspase-1, caspase-3, IL-1beta , and IL-1-RI mRNA was not different between patients and control tissues. Furthermore, we did not find detectable amounts of IL-1alpha mRNA in any of these adult myocardial tissues. On the other hand, expression of IL-18 RNA was lower in myocardium of both patient groups compared with control hearts. Furthermore, IL-1ra mRNA expression was significantly lower in tissues of DCM patients compared with ICM patients and controls. This was in line with a trend towards lower IL-1ra protein levels in myocardial tissues of DCM patients. In contrast with the adult tissues discussed above, which did not express IL-1alpha mRNA, commercially available human fetal tissue expressed IL-1alpha mRNA. On the other hand IL-1beta mRNA was present in fetal and in adult human heart tissue. Our data provide evidence for an altered ratio of IL-1/IL-1ra in DCM patients. This dysregulation may contribute to pathogenesis and/or progression of heart disease by modulating the otherwise balanced IL-1-mediated functions in cardiovascular cells.
Mol Med
PMID:Altered interleukin-1 receptor antagonist and interleukin-18 mRNA expression in myocardial tissues of patients with dilatated cardiomyopathy. 1794 66

Despite advances in immunosuppressive therapy in last few years, allograft rejection still remains the concern for kidney graft failure. Cytokines are key mediators in the induction and effector phases of all immune and inflammatory responses. They are not allospecific so both recipient as well as donor cells may be subjected to cytokine changes. We sought to ascertain whether IL-1B -511, IL-1B +3954, TNF-A -308, TGF-B Codon 10 and 25, IL-2 -330, IL-6 -174, IL-10 -1082, IL-10 -819 (SNPs), IL-1RN, IL-4 (VNTR) and TGF-B C-del (deletion) genes in two hundred subjects including recipients and their live matched donors influence renal allograft outcome. Screening was performed using PCR-RFLP and amplification refractory mutation system (ARMS-PCR). The risk for rejection appeared significant amongst recipients for pro-inflammatory cytokines IL-1B + 3954 (P = 0.045) and TNF-A -308 (0.031). No association of cytokine gene variants with rejection was observed in donors group. Further evaluating combinational effect of TNF-A (-308), IL-4 and IL-10 (-819) genes with the risk of allograft rejection showed no additive influence. Haplotype analysis between IL-1 gene cluster, TGF-B Codon 10 and 25 and IL-10 -1082 and -819 revealed that haplotypes of IL-1 gene 240-T-C, 410-T-C and 410-T-T showed very high risk among the recipients (>16, >5 and >12 folds risk respectively) when compared to donors. Interestingly, all these three haplotypes contained the variant allele T* of IL-B -511. In conclusion, our results suggest that high producing genotypes of pro-inflammatory cytokine genes in recipients have risk for allograft rejection. Lack of association in donors may be suggestive of having no conspicuous role in allograft outcome. Further analysis of diversity in haplotype variations in large populations could conceivably provide the basis for defined approaches to limit the rejections.
Mol Cell Biochem 2008 Apr
PMID:Analysis of cytokine gene polymorphisms in recipient's matched with living donors on acute rejection after renal transplantation. 1816 65

The human fallopian tube provides the environment for the first 5 days of embryonic development in vivo. The IL-1 system is involved in human embryo implantation. This study aimed to investigate IL-1beta, IL-1ra and IL-1R tI expression within the length of the human fallopian tube on mRNA- and protein-level in samples from proliferative versus secretory phase, postmenopause (PMP) samples and samples from intra- (IUP) and extrauterine pregnancies (EUP) to examine possible spatial and hormonal induced changes (fimbrial, ampullary and isthmic tube segments). On mRNA-level, IL-1beta was expressed in all samples except in PMP. IL-1R tI could be detected in all samples whereas IL-1ra was only expressed in secretory phase and the IUP sample. Immunohistochemically we could detect IL-1beta and IL-1R t1 protein in all proliferative and secretory phase samples with maximum intensity in secretory phase samples whereas IL-1ra was expressed in secretory phase samples only. Overall no spatial but temporal differences possibly due to hormonal changes could be observed suggesting a precise regulation of the IL-1 system, especially for IL-1ra and moreover a stable molecular architecture within the full length of the fallopian tube.
Mol Cell Endocrinol 2009 May 06
PMID:Interleukin-1 system in the human fallopian tube-No spatial but a temporal regulation of mRNA and protein expression. 1942 86


<< Previous 1 2 3 4 5 6 7 8 Next >>