Non-syndromic hearing loss caused by the dominant cis mutation R75Q with the recessive mutation V37I of the GJB2 (Connexin 26) gene.
Abstract
GJB2 alleles containing two cis mutations have been rarely found in non-syndromic hearing loss. Herein, we present a Korean patient with non-syndromic hearing loss caused by the R75Q cis mutation with V37I, which arose de novo in the father and was inherited by the patient. Biochemical coupling and hemichannel permeability assays were performed after molecular cloning and transfection of HEK293T cells. Student's t-tests or analysis of variance followed by Tukey's multiple comparison test was used as statistical analysis. Biochemical coupling was significantly reduced in connexin 26 (Cx26)-R75Q- an...
Source: exp Mol Med - June 22, 2015 Category: Molecular Biology Authors: Kim J, Jung J, Lee MG, Choi JY, Lee KA Tags: Exp Mol Med Source Type: research
NADPH oxidase activation contributes to native low-density lipoprotein-induced proliferation of human aortic smooth muscle cells.
Abstract
Elevated plasma concentration of native low-density lipoprotein (nLDL) is associated with vascular smooth muscle cell (VSMC) activation and cardiovascular disease. We investigated the mechanisms of superoxide generation and its contribution to pathophysiological cell proliferation in response to nLDL stimulation. Lucigenin-induced chemiluminescence was used to measure nLDL-induced superoxide production in human aortic smooth muscle cells (hAoSMCs). Superoxide production was increased by nicotinamide adenine dinucleotide phosphate (NADPH) and decreased by NADPH oxidase inhibitors in nLDL-stimulated...
Source: exp Mol Med - June 14, 2015 Category: Molecular Biology Authors: Park IH, Hwang HM, Jeon BH, Kwon HJ, Hoe KL, Kim YM, Ryoo S Tags: Exp Mol Med Source Type: research
CTCF as a multifunctional protein in genome regulation and gene expression.
Abstract
CCCTC-binding factor (CTCF) is a highly conserved zinc finger protein and is best known as a transcription factor. It can function as a transcriptional activator, a repressor or an insulator protein, blocking the communication between enhancers and promoters. CTCF can also recruit other transcription factors while bound to chromatin domain boundaries. The three-dimensional organization of the eukaryotic genome dictates its function, and CTCF serves as one of the core architectural proteins that help establish this organization. The mapping of CTCF-binding sites in diverse species has revealed that...
Source: exp Mol Med - June 7, 2015 Category: Molecular Biology Authors: Kim S, Yu NK, Kaang BK Tags: Exp Mol Med Source Type: research
Effects of sevoflurane on tight junction protein expression and PKC-α translocation after pulmonary ischemia-reperfusion injury.
In conclusion, sevoflurane pretreatment alleviated lung permeability by upregulating occludin and ZO-1 after ischemia-reperfusion. Sevoflurane pretreatment inhibited the translocation and activation of PKC-α, which also contributed to the lung-protective effect of sevoflurane.
PMID: 26045255 [PubMed - as supplied by publisher] (Source: exp Mol Med)
Source: exp Mol Med - June 7, 2015 Category: Molecular Biology Authors: Chai J, Long B, Liu X, Li Y, Han N, Zhao P, Chen W Tags: Exp Mol Med Source Type: research
An important role for peroxiredoxin II in survival of A549 lung cancer cells resistant to gefitinib.
Abstract
Redox adaptation is an important concept that explains the mechanisms by which cancer cells survive under persistent endogenous oxidative stress and become resistant to certain anticancer agents. To investigate this concept, we determined the expression levels of peroxiredoxins (Prxs), antioxidant enzymes in drug-resistant non-small cell lung carcinoma cells. Prx II was remarkably increased only in A549/GR (gefitinib-resistant) cells compared with A549 cells, consistent with methylation/demethylation. Prx II was highly methylated in the A549 cells but was demethylated in the A549/GR cells. The ele...
Source: exp Mol Med - May 30, 2015 Category: Molecular Biology Authors: Kwon T, Kyung Rho J, Cheol Lee J, Park YH, Shin HJ, Cho S, Kang YK, Kim BY, Yoon DY, Yu DY Tags: Exp Mol Med Source Type: research
MiR-155 modulates the inflammatory phenotype of intestinal myofibroblasts by targeting SOCS1 in ulcerative colitis.
Abstract
Abnormal levels of microRNA (miR)-155, which regulate inflammation and immune responses, have been demonstrated in the colonic mucosa of patients with inflammatory bowel diseases (IBD), although its role in disease pathophysiology is unknown. We investigated the role of miR-155 in the acquisition and maintenance of an activated phenotype by intestinal myofibroblasts (IMF), a key cell population contributing to mucosal damage in IBD. IMF were isolated from colonic biopsies of healthy controls, ulcerative colitis (UC) and Crohn's disease (CD) patients. MiR-155 in IMF was quantified by quantitative r...
Source: exp Mol Med - May 25, 2015 Category: Molecular Biology Authors: Pathak S, Grillo AR, Scarpa M, Brun P, D'Incà R, Nai L, Banerjee A, Cavallo D, Barzon L, Palù G, Sturniolo GC, Buda A, Castagliuolo I Tags: Exp Mol Med Source Type: research
The enhanced expression of IL-17-secreting T cells during the early progression of atherosclerosis in ApoE-deficient mice fed on a western-type diet.
Abstract
Atherosclerosis is a chronic progressive inflammatory disorder and the leading cause of cardiovascular mortality. Here we assessed the dynamic changes of T-cell-derived cytokines, such as inteferon (IFN)-γ, interleukin (IL)-17 and IL-4, during the progression of atherosclerosis in apolipoprotein E-null (ApoE(-/-)) mice, to understand the role of immune responses in different stages of atherosclerosis. Male ApoE(-/-) mice were fed a high-fat, western-type diet (WD: 21% lipid, 1.5% cholesterol) after 5 weeks of age and were compared with C57BL/6 wild-type control mice fed a standard chow diet. Athe...
Source: exp Mol Med - May 18, 2015 Category: Molecular Biology Authors: Jeon US, Choi JP, Kim YS, Ryu SH, Kim YK Tags: Exp Mol Med Source Type: research
miR-638 is a new biomarker for outcome prediction of non-small cell lung cancer patients receiving chemotherapy.
Abstract
MicroRNAs (miRNAs), a class of small non-coding RNAs, mediate gene expression by either cleaving target mRNAs or inhibiting their translation. They have key roles in the tumorigenesis of several cancers, including non-small cell lung cancer (NSCLC). The aim of this study was to investigate the clinical significance of miR-638 in the evaluation of NSCLC patient prognosis in response to chemotherapy. First, we detected miR-638 expression levels in vitro in the culture supernatants of the NSCLC cell line SPC-A1 treated with cisplatin, as well as the apoptosis rates of SPC-A1. Second, serum miR-638 ex...
Source: exp Mol Med - May 11, 2015 Category: Molecular Biology Authors: Wang F, Lou JF, Cao Y, Shi XH, Wang P, Xu J, Xie EF, Xu T, Sun RH, Rao JY, Huang PW, Pan SY, Wang H Tags: Exp Mol Med Source Type: research
The macrophage migration inhibitory factor protein superfamily in obesity and wound repair.
Abstract
The rising number of obese individuals has become a major burden to the healthcare systems worldwide. Obesity includes not only the increase of adipose tissue mass but importantly also the altered cellular functions that collectively lead to a chronic state of adipose tissue inflammation, insulin resistance and impaired wound healing. Adipose tissue undergoing chronic inflammation shows altered cytokine expression and an accumulation of adipose tissue macrophages (ATM). The macrophage migration inhibitory factor (MIF) superfamily consists of MIF and the recently identified homolog D-dopachrome tau...
Source: exp Mol Med - May 3, 2015 Category: Molecular Biology Authors: Kim BS, Pallua N, Bernhagen J, Bucala R Tags: Exp Mol Med Source Type: research
Polyphenols isolated from Broussonetia kazinoki prevent cytokine-induced β-cell damage and the development of type 1 diabetes.
In this study, we investigated the effects of kazinol C and isokazinol D isolated from Broussonetia kazinoki on the β-cell viability and function. RINm5F cells and primary islets were used for in vitro and ex vivo cytokine toxicity experiments, respectively. For type 1 diabetes induction, mice were injected with multiple low-dose streptozotocin (MLDS). Cytokine-induced toxicity was completely abolished in both RINm5F cells and islets that were pretreated with either kazinol C or isokazinol D. Both kazinols inhibited the NF-κB signaling pathway, thereby inhibiting cytokine-mediated iNOS induction, nitric oxide production,...
Source: exp Mol Med - April 26, 2015 Category: Molecular Biology Authors: Bae UJ, Jang HY, Lim JM, Hua L, Ryu JH, Park BH Tags: Exp Mol Med Source Type: research
Gephyrin: a central GABAergic synapse organizer.
Abstract
Gephyrin is a central element that anchors, clusters and stabilizes glycine and γ-aminobutyric acid type A receptors at inhibitory synapses of the mammalian brain. It self-assembles into a hexagonal lattice and interacts with various inhibitory synaptic proteins. Intriguingly, the clustering of gephyrin, which is regulated by multiple posttranslational modifications, is critical for inhibitory synapse formation and function. In this review, we summarize the basic properties of gephyrin and describe recent findings regarding its roles in inhibitory synapse formation, function and plasticity. We wi...
Source: exp Mol Med - April 18, 2015 Category: Molecular Biology Authors: Choii G, Ko J Tags: Exp Mol Med Source Type: research
Polyubiquitin chain-dependent protein degradation in TRIM30 cytoplasmic bodies.
Abstract
Viral infection induces numerous tripartite motif (TRIM) proteins to control antiviral immune signaling and viral replication. Particularly, SPRY-containing TRIM proteins are found only in vertebrates and they control target protein degradation by their RING-finger and SPRY domains, and proper cytoplasmic localization. To understand TRIM30 function, we analyzed its localization pattern and putative roles of its RING-finger and SPRY domains. We found that TRIM30 is located in actin-mediated cytoplasmic bodies and produces colocalized ubiquitin chains in SPRY domain- and RING-finger domain-dependent...
Source: exp Mol Med - April 18, 2015 Category: Molecular Biology Authors: Choi UY, Choi WY, Hur JY, Kim YJ Tags: Exp Mol Med Source Type: research
Effects of MBL2 polymorphisms in patients with diisocyanate-induced occupational asthma.
Abstract
Diisocyanate (DI) is the most common cause of occupational asthma (OA) in Korea. Mannose-binding lectin (MBL) initiates the lectin complement activation pathway following oxidative stress and plays an important role in the regulation of inflammatory processes. To determine whether there is a genetic association between MBL2 polymorphisms and DI-OA, 99 patients with DI-OA, 99 asymptomatic exposed controls (AECs) and 144 unexposed normal controls were enrolled in this study. Three polymorphisms (-554 G>C, -431A>C and -225 G>C) in the MBL2 promoter were genotyped, and serum MBL levels were d...
Source: exp Mol Med - April 11, 2015 Category: Molecular Biology Authors: Kim SH, Bae SJ, Palikhe S, Ye YM, Park HS Tags: Exp Mol Med Source Type: research
Toward understanding the role of the neuron-specific BAF chromatin remodeling complex in memory formation.
Abstract
The long-term storage of memory requires the finely tuned coordination of intracellular signaling with the transcriptional, translational and epigenetic regulations of gene expression. Among the epigenetic mechanisms, however, we know relatively little about the involvement of chromatin remodeling-dependent control of gene expression in cognitive brain functions, compared with our knowledge of other such mechanisms (for example, histone modifications and DNA methylation). A few recent studies have implicated the Brm/Brg-associated factor (BAF) chromatin-remodeling complex, a mammalian homolog of t...
Source: exp Mol Med - April 6, 2015 Category: Molecular Biology Authors: Choi KY, Yoo M, Han JH Tags: Exp Mol Med Source Type: research
MyD88-BLT2-dependent cascade contributes to LPS-induced interleukin-6 production in mouse macrophage.
Abstract
Endotoxic responses to bacterial lipopolysaccharide (LPS) are triggered by Toll-like receptor 4 (TLR4) and involve the production of inflammatory mediators, including interleukin-6 (IL-6), by macrophages. The detailed mechanism of IL-6 production by macrophages in response to LPS has remained unclear, however. We now show that LPS induces IL-6 synthesis in mouse peritoneal macrophages via the leukotriene B4 receptor BLT2. Our results suggest that TLR4-MyD88 signaling functions upstream of BLT2 and that the generation of reactive oxygen species (ROS) by NADPH oxidase 1 (Nox1) and consequent activat...
Source: exp Mol Med - April 6, 2015 Category: Molecular Biology Authors: Lee AJ, Cho KJ, Kim JH Tags: Exp Mol Med Source Type: research
