Constitutive stabilization of hypoxia-inducible factor alpha selectively promotes the self-renewal of mesenchymal progenitors and maintains mesenchymal stromal cells in an undifferentiated state.
In this study, to further define the significance of Hif-1α in MSC function during their self-renewal and terminal differentiation, we established adult bone marrow (BM)-derived MSCs that are able to sustain high level expression of ubiquitin-resistant Hif-1α during such long-term biological processes. Using this model, we show that the stabilization of Hif-1α proteins exerts a selective influence on colony-forming mesenchymal progenitors promoting their self-renewal and proliferation, without affecting the proliferation of the MSC mass population. Moreover, Hif-1α stabilization in MSCs led to the induction of pluripot...
Source: exp Mol Med - September 29, 2013 Category: Molecular Biology Authors: Park IH, Kim KH, Choi HK, Shim JS, Whang SY, June Hahn S, Kwon OJ, Oh IH Tags: Exp Mol Med Source Type: research
MicroRNAs: their involvement in fibrosis pathogenesis and use as diagnostic biomarkers in scleroderma.
Abstract
miRNAs are important post-transcriptional regulators. The aberrant expression of miRNAs is strongly associated with the initiation and progression of pathophysiologic processes in a wide range of human diseases. Scleroderma (systemic sclerosis; SSc) is a highly heterogeneous autoimmune disease that includes the progressive fibrotic replacement of normal tissue architecture in multiple organs. Our previous studies have suggested that SSc skin tissues display a different miRNA expression signature than that found in normal controls. miRNAs with pro- or antifibrotic properties are found to be dysregu...
Source: exp Mol Med - September 24, 2013 Category: Molecular Biology Authors: Zhu H, Luo H, Zuo X Tags: Exp Mol Med Source Type: research
U6 is unsuitable for normalization of serum miRNA levels in patients with sepsis or liver fibrosis.
Abstract
MicroRNA (miRNA) levels in serum have recently emerged as potential novel biomarkers for various diseases. miRNAs are routinely measured by standard quantitative real-time PCR (qPCR); however, the high sensitivity of qPCR demands appropriate normalization to correct for nonbiological variation. Presently, RNU6B (U6) is used for data normalization of circulating miRNAs in many studies. However, it was suggested that serum levels of U6 themselves might differ between individuals. Therefore, no consensus has been reached on the best normalization strategy in 'circulating miRNA'. We analyzed U6 levels...
Source: exp Mol Med - September 24, 2013 Category: Molecular Biology Authors: Benz F, Roderburg C, Vargas Cardenas D, Vucur M, Gautheron J, Koch A, Zimmermann H, Janssen J, Nieuwenhuijsen L, Luedde M, Frey N, Tacke F, Trautwein C, Luedde T Tags: Exp Mol Med Source Type: research
The immune-stimulating peptide WKYMVm has therapeutic effects against ulcerative colitis.
In this study, we examined the therapeutic effects of an immune-stimulating peptide, WKYMVm, in ulcerative colitis. The administration of WKYMVm to dextran sodium sulfate (DSS)-treated mice reversed decreases in body weight, bleeding score and stool score in addition to reversing DSS-induced mucosa destruction and shortened colon. The WKYMVm-induced therapeutic effect against ulcerative colitis was strongly inhibited by a formyl peptide receptor (FPR) 2 antagonist, WRWWWW, indicating the crucial role of FPR2 in this effect. Mechanistically, WKYMVm effectively decreases intestinal permeability by stimulating colon epithelia...
Source: exp Mol Med - September 15, 2013 Category: Molecular Biology Authors: Kim SD, Kwon S, Lee SK, Kook M, Lee HY, Song KD, Lee HK, Baek SH, Park CB, Bae YS Tags: Exp Mol Med Source Type: research
Brain site-specific proteome changes in aging-related dementia.
This study is aimed at gaining insights into the brain site-specific proteomic senescence signature while comparing physiologically aged brains with aging-related dementia brains (for example, Alzheimer's disease (AD)). Our study of proteomic differences within the hippocampus (Hp), parietal cortex (pCx) and cerebellum (Cb) could provide conceptual insights into the molecular mechanisms involved in aging-related neurodegeneration. Using an isobaric tag for relative and absolute quantitation (iTRAQ)-based two-dimensional liquid chromatography coupled with tandem mass spectrometry (2D-LC-MS/MS) brain site-specific proteomic ...
Source: exp Mol Med - September 10, 2013 Category: Molecular Biology Authors: Manavalan A, Mishra M, Feng L, Sze SK, Akatsu H, Heese K Tags: Exp Mol Med Source Type: research
Intermedin1-53 attenuates vascular smooth muscle cell calcification by inhibiting endoplasmic reticulum stress via cyclic adenosine monophosphate/protein kinase A pathway.
In conclusion, IMD1-53 attenuated VSMC calcification by inhibiting ER stress through cAMP/PKA signalling.
PMID: 24006303 [PubMed - as supplied by publisher] (Source: exp Mol Med)
Source: exp Mol Med - September 4, 2013 Category: Molecular Biology Authors: Chang JR, Duan XH, Zhang BH, Teng X, Zhou YB, Liu Y, Yu YR, Zhu Y, Tang CS, Qi YF Tags: Exp Biol Med (Maywood) Source Type: research
Phospholipase D inhibitor enhances radiosensitivity of breast cancer cells.
Abstract
Radiation and drug resistance remain the major challenges and causes of mortality in the treatment of locally advanced, recurrent and metastatic breast cancer. Dysregulation of phospholipase D (PLD) has been found in several human cancers and is associated with resistance to anticancer drugs. In the present study, we evaluated the effects of PLD inhibition on cell survival, cell death and DNA damage after exposure to ionizing radiation (IR). Combined IR treatment and PLD inhibition led to an increase in the radiation-induced apoptosis of MDA-MB-231 metastatic breast cancer cells. The selective inh...
Source: exp Mol Med - September 1, 2013 Category: Molecular Biology Authors: Cheol Son J, Woo Kang D, Mo Yang K, Choi KY, Gen Son T, Min do S Tags: Exp Mol Med Source Type: research
Signaling mechanisms of glucose-induced F-actin remodeling in pancreatic islet β cells.
Abstract
The maintenance of whole-body glucose homeostasis is critical for survival, and is controlled by the coordination of multiple organs and endocrine systems. Pancreatic islet β cells secrete insulin in response to nutrient stimuli, and insulin then travels through the circulation promoting glucose uptake into insulin-responsive tissues such as liver, skeletal muscle and adipose. Many of the genes identified in human genome-wide association studies of diabetic individuals are directly associated with β cell survival and function, giving credence to the idea that β-cell dysfunction is central to th...
Source: exp Mol Med - August 27, 2013 Category: Molecular Biology Authors: Kalwat MA, Thurmond DC Tags: Exp Mol Med Source Type: research
Increased malondialdehyde concentration and reduced total antioxidant capacity in aqueous humor and blood samples from patients with glaucoma.
CONCLUSIONS: Our data further support the hypothesis that oxidative stress and decreased antioxidant defenses are involved in glaucoma. High-performance liquid chromatography appears to be an effective and sensitive method to detect altered levels of oxidative stress markers in glaucoma patients.
PMID: 23946639 [PubMed - in process] (Source: exp Mol Med)
Source: exp Mol Med - August 22, 2013 Category: Molecular Biology Authors: Nucci C, Di Pierro D, Varesi C, Ciuffoletti E, Russo R, Gentile R, Cedrone C, Duran MD, Coletta M, Mancino R Tags: Mol Vis Source Type: research
LRRK2 phosphorylates Snapin and inhibits interaction of Snapin with SNAP-25.
Abstract
Leucine-rich repeat kinase 2 (LRRK2) is a gene that, upon mutation, causes autosomal-dominant familial Parkinson's disease (PD). Yeast two-hybrid screening revealed that Snapin, a SNAP-25 (synaptosomal-associated protein-25) interacting protein, interacts with LRRK2. An in vitro kinase assay exhibited that Snapin is phosphorylated by LRRK2. A glutathione-S-transferase (GST) pull-down assay showed that LRRK2 may interact with Snapin via its Ras-of-complex (ROC) and N-terminal domains, with no significant difference on interaction of Snapin with LRRK2 wild type (WT) or its pathogenic mutants. Furthe...
Source: exp Mol Med - August 22, 2013 Category: Molecular Biology Authors: Yun HJ, Park J, Ho DH, Kim H, Kim CH, Oh H, Ga I, Seo H, Chang S, Son I, Seol W Tags: Exp Mol Med Source Type: research
TDAG51 deficiency promotes oxidative stress-induced apoptosis through the generation of reactive oxygen species in mouse embryonic fibroblasts.
In this study, we investigated the role of TDAG51 in oxidative stress-induced apoptotic cell death in mouse embryonic fibroblasts (MEFs). TDAG51 expression was highly increased by oxidative stress responses. In response to oxidative stress, the production of intracellular reactive oxygen species was significantly enhanced in TDAG51-deficient MEFs, resulting in the activation of caspase-3. Thus, TDAG51 deficiency promotes apoptotic cell death in MEFs, and these results indicate that TDAG51 has a protective role in oxidative stress-induced cell death in MEFs.
PMID: 23928855 [PubMed - in process] (Source: exp Mol Med)
Source: exp Mol Med - August 11, 2013 Category: Molecular Biology Authors: Park ES, Kim J, Ha TU, Choi JS, Soo Hong K, Rho J Tags: Exp Mol Med Source Type: research
Characterizing affinity epitopes between prion protein and β-amyloid using an epitope mapping immunoassay.
In conclusion, charged clusters and hydrophobic regions of the prion protein were involved in binding to β-amyloid1-40 and 1-42. The 3D structure appears to be necessary for β-amyloid to interact with prion protein. In the future, these binding sites may be utilized for 3D structure modeling, as well as for the pharmaceutical intervention of Alzheimer's disease.
PMID: 23907583 [PubMed - in process] (Source: exp Mol Med)
Source: exp Mol Med - August 6, 2013 Category: Molecular Biology Authors: Kang M, Yeon Kim S, An SS, Ran Ju Y Tags: Exp Mol Med Source Type: research
AMP-activated protein kinase as a key molecular link between metabolism and clockwork.
Abstract
Circadian clocks regulate behavioral, physiological and biochemical processes in a day/night cycle. Circadian oscillators have an essential role in the coordination of physiological processes with the cyclic changes in the physical environment. Such mammalian circadian clocks composed of the positive components (BMAL1 and CLOCK) and the negative components (CRY and PERIOD (PER)) are regulated by a negative transcriptional feedback loop in which PER is rate-limiting for feedback inhibition. In addition, posttranslational modification of these components is critical for setting or resetting the circ...
Source: exp Mol Med - August 1, 2013 Category: Molecular Biology Authors: Lee Y, Kim EK Tags: Exp Mol Med Source Type: research
Reactive oxygen species regulate context-dependent inhibition of NFAT5 target genes.
In this study we identified a novel context-dependent suppression of NFAT5 target gene expression in RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS) or a high salt (NaCl) concentration. Although LPS and NaCl both used NFAT5 as a core transcription factor, these stimuli mutually inhibited distinct sets of NFAT5 targets within the cells. Although reactive oxygen species (ROS) are essential for this inhibition, the source of ROS differed depending on the context: mitochondria for high salt and xanthine oxidase for TLRs. Specifically, the high salt-induced suppression of interleukin-6 (IL-6) production was media...
Source: exp Mol Med - July 27, 2013 Category: Molecular Biology Authors: Kim NH, Hong BK, Choi SY, Moo Kwon H, Cho CS, Yi EC, Kim WU Tags: Exp Mol Med Source Type: research
A known expressed sequence tag, BM742401, is a potent lincRNA inhibiting cancer metastasis.
Abstract
Long intergenic non-coding RNAs (lincRNAs) have historically been ignored in cancer biology. However, thousands of lincRNAs have been identified in mammals using recently developed genomic tools, including microarray and high-throughput RNA sequencing (RNA-seq). Several of the lincRNAs identified have been well characterized for their functions in carcinogenesis. Here we performed RNA-seq experiments comparing gastric cancer with normal tissues to find differentially expressed transcripts in intergenic regions. By analyzing our own RNA-seq and public microarray data, we identified 31 transcripts, ...
Source: exp Mol Med - July 18, 2013 Category: Molecular Biology Authors: Park SM, Park SJ, Kim HJ, Kwon OH, Kang TW, Sohn HA, Kim SK, Moo Noh S, Song KS, Jang SJ, Sung Kim Y, Kim SY Tags: Exp Mol Med Source Type: research
