Effect of the combination of metformin and fenofibrate on glucose homeostasis in diabetic Goto-Kakizaki rats.
In conclusion, fenofibrate did not confer any beneficial effect on glucose homeostasis but reduced metformin's glucose-lowering activity in GK rats, thus discouraging the addition of fenofibrate to metformin to improve glycemic control.
PMID: 23827952 [PubMed - as supplied by publisher] (Source: exp Mol Med)
Source: exp Mol Med - July 8, 2013 Category: Molecular Biology Authors: Oh TJ, Shin JY, Kang GH, Park KS, Cho YM Tags: Exp Mol Med Source Type: research
Synapsin-1 and tau reciprocal O-GlcNAcylation and phosphorylation sites in mouse brain synaptosomes.
Abstract
O-linked N-acetylglucosamine (O-GlcNAc) represents a key regulatory post-translational modification (PTM) that is reversible and often reciprocal with phosphorylation of serine and threonine at the same or nearby residues. Although recent technical advances in O-GlcNAc site-mapping methods combined with mass spectrometry (MS) techniques have facilitated study of the fundamental roles of O-GlcNAcylation in cellular processes, an efficient technique for examining the dynamic, reciprocal relationships between O-GlcNAcylation and phosphorylation is needed to provide greater insights into the regulator...
Source: exp Mol Med - June 29, 2013 Category: Molecular Biology Authors: Kang MJ, Kim C, Jeong H, Cho BK, Ryou AL, Hwang D, Mook-Jung I, Yi EC Tags: Exp Mol Med Source Type: research
Oxidative stress is associated with the number of components of metabolic syndrome: LIPGENE study.
Abstract
Previous evidence supports the important role that oxidative stress (OxS) plays in metabolic syndrome (MetS)-related manifestations. We determined the relationship between the number of MetS components and the degree of OxS in MetS patients. In this comparative cross-sectional study from the LIPGENE cohort, a total of 91 MetS patients (43 men and 48 women; aged between 45 and 68 years) were divided into four groups based on the number of MetS components: subjects with 2, 3, 4 and 5 MetS components (n=20, 31, 28 and 12, respectively). We measured ischemic reactive hyperemia (IRH), plasma levels of ...
Source: exp Mol Med - June 24, 2013 Category: Molecular Biology Authors: Yubero-Serrano EM, Delgado-Lista J, Peña-Orihuela P, Perez-Martinez P, Fuentes F, Marin C, Tunez I, Jose Tinahones F, Perez-Jimenez F, Roche HM, Lopez-Miranda J Tags: Exp Mol Med Source Type: research
Phosphoinositides and PDZ domain scaffolds.
Abstract
The discovery that PSD-95/Discs large/ZO-1 (PDZ) domains can function as lipid-binding modules, in particular interacting with phosphoinositides (PIs), was made more than 10 years ago (Mol Cell 9(6): 1215-1225, 2002). Confirmatory studies and a series of functional follow-ups established PDZ domains as dual specificity modules displaying both peptide and lipid binding, and prompted a rethinking of the mode of action of PDZ domains in the control of cell signaling. In this chapter, after introducing PDZ domains, PIs and methods for studying protein-lipid interactions, we focus on (i) the prevalence...
Source: exp Mol Med - June 20, 2013 Category: Molecular Biology Authors: Wawrzyniak AM, Kashyap R, Zimmermann P Tags: Adv Exp Med Biol Source Type: research
Functional proteomics, human genetics and cancer biology of GIPC family members.
Abstract
GIPC1, GIPC2 and GIPC3 consist of GIPC homology 1 (GH1) domain, PDZ domain and GH2 domain. The regions around the GH1 and GH2 domains of GIPC1 are involved in dimerization and interaction with myosin VI (MYO6), respectively. The PDZ domain of GIPC1 is involved in interactions with transmembrane proteins [IGF1R, NTRK1, ADRB1, DRD2, TGFβR3 (transforming growth factorβ receptor type III), SDC4, SEMA4C, LRP1, NRP1, GLUT1, integrin α5 and VANGL2], cytosolic signaling regulators (APPL1 and RGS19) and viral proteins (HBc and HPV-18 E6). GIPC1 is an adaptor protein with dimerizing ability that loads PD...
Source: exp Mol Med - June 11, 2013 Category: Molecular Biology Authors: Katoh M Tags: Exp Mol Med Source Type: research
Retraction: Protective effects of transduced Tat-DJ-1 protein against oxidative stress and ischemic brain injury.
PMID: 23703572 [PubMed - in process] (Source: exp Mol Med)
Source: exp Mol Med - May 28, 2013 Category: Molecular Biology Authors: Jeong HJ, Kim DW, Kim MJ, Woo SJ, Kim HR, Kim SM, Jo HS, Hwang HS, Kim DS, Cho SW, Won MH, Han KH, Park J, Eum WS, Choi SY Tags: Exp Mol Med Source Type: research
B-cell translocation gene 2 positively regulates GLP-1-stimulated insulin secretion via induction of PDX-1 in pancreatic β-cells.
Abstract
Glucagon-like peptide-1 (GLP-1) is a potent glucoincretin hormone and an important agent for the treatment of type 2 diabetes. Here we demonstrate that B-cell translocation gene 2 (BTG2) is a crucial regulator in GLP-1-induced insulin gene expression and insulin secretion via upregulation of pancreatic duodenal homeobox-1 (PDX-1) in pancreatic β-cells. GLP-1 treatment significantly increased BTG2, PDX-1 and insulin gene expression in pancreatic β-cells. Notably, adenovirus-mediated overexpression of BTG2 significantly elevated insulin secretion, as well as insulin and PDX-1 gene expression. Phys...
Source: exp Mol Med - May 28, 2013 Category: Molecular Biology Authors: Hwang SL, Kwon O, Kim SG, Lee IK, Kim YD Tags: Exp Mol Med Source Type: research
Different uptake of gentamicin through TRPV1 and TRPV4 channels determines cochlear hair cell vulnerability.
We report here that gentamicin caused rodent cochlear hair cell damages in a time- and dose-dependent manner. Hair cells at the basal turn were more vulnerable to gentamicin than those at the apical turn. Gentamicin-conjugated Texas Red (GTTR) uptake was predominant in basal turn hair cells in neonatal rats. Transient receptor potential vanilloid 1 (TRPV1) and 4 (TRPV4) expression was confirmed in the cuticular plate, stereocilia and hair cell body of inner hair cells and outer hair cells. The involvement of TRPV1 and TRPV4 in gentamicin trafficking of hair cells was confirmed by exogenous calcium treatment and TRPV inhibi...
Source: exp Mol Med - May 23, 2013 Category: Molecular Biology Authors: Lee JH, Park C, Kim SJ, Kim HJ, Oh GS, Shen A, So HS, Park R Tags: Exp Mol Med Source Type: research
Differentiated miRNA expression and validation of signaling pathways in apoE gene knockout mice by cross-verification microarray platform.
Abstract
The microRNA (miRNA) regulation mechanisms associated with atherosclerosis are largely undocumented. Specific selection and efficient validation of miRNA regulation pathways involved in atherosclerosis development may be better assessed by contemporary microarray platforms applying cross-verification methodology. A screening platform was established using both miRNA and genomic microarrays. Microarray analysis was then simultaneously performed on pooled atherosclerotic aortic tissues from 10 Apolipoprotein E (apoE) knockout mice (apoE-/-) and 10 healthy C57BL/6 (B6) mice. Differentiated miRNAs wer...
Source: exp Mol Med - May 23, 2013 Category: Molecular Biology Authors: Han H, Wang YH, Qu GJ, Sun TT, Li FQ, Jiang W, Luo SS Tags: Exp Mol Med Source Type: research
A genetic effect of IL-5 receptor α polymorphism in patients with aspirin-exacerbated respiratory disease.
Abstract
Persistent eosinophil activation in both the upper and lower airway mucosa is a central feature of aspirin-exacerbated respiratory disease (AERD). Eosinophil activation and survival are profoundly influenced by interleukin 5 (IL-5) and its receptor, IL-5R. In patients susceptible to allergic disorders, IL-5 receptor α (IL5RA) polymorphisms have been reported; however, an association with AERD remains unclear. We hypothesize that IL5RA polymorphisms may contribute to eosinophil activation in AERD patients. We recruited 139 AERD patients, 171 aspirin-tolerant asthma patients and 160 normal controls...
Source: exp Mol Med - May 23, 2013 Category: Molecular Biology Authors: Losol P, Kim SH, Seob Shin Y, Min Ye Y, Park HS Tags: Exp Mol Med Source Type: research
G protein signaling in the parasite Entamoeba histolytica.
Abstract
The parasite Entamoeba histolytica causes amebic colitis and systemic amebiasis. Among the known amebic factors contributing to pathogenesis are signaling pathways involving heterotrimeric and Ras superfamily G proteins. Here, we review the current knowledge of the roles of heterotrimeric G protein subunits, Ras, Rho and Rab GTPase families in E. histolytica pathogenesis, as well as of their downstream signaling effectors and nucleotide cycle regulators. Heterotrimeric G protein signaling likely modulates amebic motility and attachment to and killing of host cells, in part through activation of an...
Source: exp Mol Med - May 23, 2013 Category: Molecular Biology Authors: Bosch DE, Siderovski DP Tags: Exp Mol Med Source Type: research
Phosphatidylinositol 4-phosphate 5-kinase α negatively regulates nerve growth factor-induced neurite outgrowth in PC12 cells.
In this study, we addressed whether PIP5Kα, an isoform of PIP5K, could have a role in neurite outgrowth induced by nerve growth factor (NGF). For this purpose, we knocked down PIP5Kα in PC12 rat pheochromocytoma cells by stable expression of PIP5Kα microRNA that significantly reduced PIP5Kα expression and PIP2 level. Interestingly, NGF-induced neurite outgrowth was more prominent in PIP5Kα-knockdown (KD) cells than in control cells. Conversely, add-back of PIP5Kα into PIP5Kα KD cells abrogated the effect of NGF on neurite outgrowth. NGF treatment activated PI 3-kinase (PI3K)/Akt pathway, which seemed to be associate...
Source: exp Mol Med - May 23, 2013 Category: Molecular Biology Authors: Liu T, Lee SY Tags: Exp Mol Med Source Type: research
Glyceollins, a novel class of soybean phytoalexins, inhibit SCF-induced melanogenesis through attenuation of SCF/c-kit downstream signaling pathways.
Abstract
The anti-melanogenesis effect of glyceollins was examined by melanin synthesis, tyrosinase activity assay in zebrafish embryos and in B16F10 melanoma cells. When developing zebrafish embryos were treated with glyceollins, pigmentation of the embryos, melanin synthesis and tyrosinase activity were all decreased compared with control zebrafish embryos. In situ expression of a pigment cell-specific gene, Sox10, was dramatically decreased by glyceollin treatment in the neural tubes of the trunk region of the embryos. Stem cell factor (SCF)/c-kit signaling pathways as well as expression of microphthalm...
Source: exp Mol Med - May 23, 2013 Category: Molecular Biology Authors: Shin SH, Lee YM Tags: Exp Mol Med Source Type: research
ISG15: leading a double life as a secreted molecule.
Abstract
ISG15 is a well-known intracellular ubiquitin-like molecule involved in ISGylation. However, a recent study has revived the notion first put forward two decades ago that ISG15 is also a secreted molecule. Human neutrophils, monocytes and lymphocytes can release ISG15, even though this protein has no detectable signal peptide sequence. ISG15 has also been found in the secretory granules of granulocytes. The mechanism underlying ISG15 secretion is unknown. Secreted ISG15 acts on at least T and natural killer (NK) lymphocytes, in which it induces interferon (IFN)-γ production. However, the mechanism...
Source: exp Mol Med - May 23, 2013 Category: Molecular Biology Authors: Bogunovic D, Boisson-Dupuis S, Casanova JL Tags: Exp Mol Med Source Type: research
The colchicine derivative CT20126 shows a novel microtubule-modulating activity with apoptosis.
Abstract
New colchicine analogs have been synthesized with the aim of developing stronger potential anticancer activities. Among the analogs, CT20126 has been previously reported to show immunosuppressive activities. Here, we report that CT20126 also shows potential anticancer effects via an unusual mechanism: the modulation of microtubule integrity and cell cycle arrest at the G2/M phase before apoptosis. When we treated COS-7 cells with CT20126 (5 μM), the normal thread-like microtubules were disrupted into tubulin dimers within 10 min and thereafter repolymerized into short, thick filaments. In con...
Source: exp Mol Med - May 23, 2013 Category: Molecular Biology Authors: Kim SK, Cho SM, Kim H, Seok H, Kim SO, Kyu Kwon T, Chang JS Tags: Exp Mol Med Source Type: research
