Biochemical and Biophysical Research Communications (Biochem Biophys Res Comm )

Publisher: Elsevier

Description

Biochemical and Biophysical Research Communications is the premier international journal devoted to the very rapid dissemination (six weeks) of timely and significant experimental results in the diverse fields of biological research. Frequent publication (36 issues per year) ensures a steady stream of information. The development of the "Breakthroughs and Views" section brings the minireview format to the journal. In addition, the editors have expanded the journalís scope. Research Areas now include: Biochemistry Cell Biology; Developmental Biology; Immunology; Neurobiology; Biophysics; Molecular Biology; Plant Biology.

  • Impact factor
    2.28
  • 5-year impact
    2.50
  • Cited half-life
    8.50
  • Immediacy index
    0.40
  • Eigenfactor
    0.14
  • Article influence
    0.78
  • Website
    Biochemical and Biophysical Research Communications website
  • Other titles
    Biochemical and biophysical research communications (Online), Biochemical and biophysical research communications
  • ISSN
    1090-2104
  • OCLC
    35247010
  • Material type
    Document, Periodical, Internet resource
  • Document type
    Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

Elsevier

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author can archive a post-print version
  • Conditions
    • Pre-print allowed on any website or open access repository
    • Voluntary deposit by author of authors post-print allowed on authors' personal website, arXiv.org or institutions open scholarly website including Institutional Repository, without embargo, where there is not a policy or mandate
    • Deposit due to Funding Body, Institutional and Governmental policy or mandate only allowed where separate agreement between repository and the publisher exists.
    • Permitted deposit due to Funding Body, Institutional and Governmental policy or mandate, may be required to comply with embargo periods of 12 months to 48 months .
    • Set statement to accompany deposit
    • Published source must be acknowledged
    • Must link to journal home page or articles' DOI
    • Publisher's version/PDF cannot be used
    • Articles in some journals can be made Open Access on payment of additional charge
    • NIH Authors articles will be submitted to PubMed Central after 12 months
    • Publisher last contacted on 18/10/2013
  • Classification
    ​ green

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: ATP-binding cassette transporter D2 (D2) is an ABC half transporter that is thought to promote the transport of very long-chain fatty acyl-CoAs into peroxisomes. Both D2 and peroxisomes increase during adipogenesis. Although peroxisomes are essential to both catabolic and anabolic lipid metabolism, their function, and that of D2, in adipose tissues remain largely unknown. Here, we investigated the D2 localization and the proteome of D2-containing organelles, in adipose tissue. Centrifugation of mouse adipose homogenates generated a fraction enriched with D2, but deficient in peroxisome markers including catalase, PEX19, and ABCD3 (D3). Electron microscopic imaging of this fraction confirmed the presence of D2 protein on an organelle with a dense matrix and a diameter of ∼200 nm, the typical structure and size of a microperoxisome. D2 and PEX19 antibodies recognized distinct structures in mouse adipose. Immunoisolation of the D2-containing compartment confirmed the scarcity of PEX19 and proteomic profiling revealed the presence of proteins associated with peroxisome, endoplasmic reticulum (ER), and mitochondria. D2 is localized to a distinct class of peroxisomes that lack many peroxisome proteins, and may associate physically with mitochondria and the ER.
    Biochemical and Biophysical Research Communications 11/2014;
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    ABSTRACT: This study investigates the role of impaired proliferation, altered cell cycle arrest, and defective autophagy flux of corneal fibroblasts in granular corneal dystrophy type 2 (GCD2) pathogenesis. The proliferation rates of homozygous (HO) GCD2 corneal fibroblasts at 72 h, 96 h, and 120 h were significantly lower (1.102 ± 0.027, 1.397 ± 0.039, and 1.527 ± 0.056, respectively) than those observed for the wild-type (WT) controls (1.441 ± 0.029, 1.758 ± 0.043, and 2.003 ± 0.046, respectively). Flow cytometry indicated a decreased G1 cell cycle progression and the accumulation of cells in the S and G2/M phases in GCD2 cells. These accumulations were associated with decreased levels of Cyclin A1, B1, and E1, and increased expression of p16 and p27. p21 and p53 expression was also significantly lower in GCD2 cells compared to the WT. Interestingly, treatment with the autophagy flux inhibitor, bafilomycin A1, resulted in similarly decreased Cyclin A1, B1, D1, and p53 expression in WT fibroblasts. Furthermore, similar findings, including a decrease in Cyclin A1, B1, and D1 and an increase in p16 and p27 expression were observed in autophagy-related 7 (Atg7; known to be essential for autophagy) gene knockout cells. These data provide new insight concerning the role of autophagy in cell cycle arrest and cellular proliferation, uncovering a number of novel therapeutic possibilities for GCD2 treatment.
    Biochemical and Biophysical Research Communications 11/2014;
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    ABSTRACT: RIPK3 is a key molecule for necroptosis, initially characterized by necrotic cell death morphology and the activation of autophagy. Cell death and autophagic signaling are believed to tightly regulate each other. However, the associated recruitment of signaling proteins remains poorly understood. p62/sequestosome-1 is a selective autophagy substrate and a selective receptor for ubiquitinated proteins. In this study, we illustrated that both mouse and human RIPK3 mediate p62 cleavage and that RIPK3 interacts with p62, resulting in complex formation. In addition, RIPK3-dependent p62 cleavage is restricted by the inhibition of caspases, especially caspase-8. Moreover, overexpression of A20, a ubiquitin-editing enzyme and an inhibitor of caspase-8 activity, inhibits RIPK3-dependent p62 cleavage. To further investigate the potential role of RIPK3 in selective autophagy, we analyzed p62–LC3 complex formation, revealing that RIPK3 prevents the localization of LC3 and ubiquitinated proteins to the p62 complex. In addition, RIPK3-dependent p62–LC3 complex disruption is regulated by caspase inhibition. Taken together, these results demonstrated that RIPK3 interacts with p62 and regulates p62–LC3 complex formation. These findings suggested that RIPK3 serves as a negative regulator of selective autophagy and provides new insights into the mechanism by which RIPK3 regulates autophagic signaling.
    Biochemical and Biophysical Research Communications 11/2014;
  • Maria Winiewska, Małgorzata Makowska, Piotr Maj, Monika Wielechowska, Maria Bretner, Jarosław Poznański, David Shugar
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    ABSTRACT: The interaction of human CK2α with a series of tetrabromobenzotriazole (TBBt) and tetrabromobenzimidazole (TBBz) analogs, in which one of the bromine atoms proximal to the triazole/imidazole ring is replaced by a methyl group, was studied by biochemical (IC50) and biophysical methods (thermal stability of protein–ligand complex monitored by DSC and fluorescence). Two newly synthesized tri-bromo derivatives display inhibitory activity comparable to that of the reference compounds, TBBt and TBBz, respectively. DSC analysis of the stability of protein–ligand complexes shows that the heat of ligand binding (Hbind) is driven by intermolecular electrostatic interactions involving the triazole/imidazole ring, as indicated by a strong correlation between Hbind and ligand pKa. Screening, based on fluorescence-monitored thermal unfolding of protein–ligand complexes, gave comparable results, clearly identifying ligands that most strongly bind to the protein. Overall results, additionally supported by molecular modeling, confirm that a balance of hydrophobic and electrostatic interactions contribute predominantly, relative to possible intermolecular halogen bonding, in binding of the ligands to the CK2α ATP-binding site.
    Biochemical and Biophysical Research Communications 11/2014;
  • Florian Weinberger, Dennis Mehrkens, Jutta Starbatty, Philipp Nicol, Thomas Eschenhagen
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    ABSTRACT: Rationale: Islet-1 positive (Islet-1+) cardiac progenitor cells give rise to the right ventricle, atria and outflow tract during murine cardiac development. In the adult heart Islet-1 expression is limited to parasympathetic neurons, few cardiomyocytes, smooth muscle cells, within the proximal aorta and pulmonary artery and sinoatrial node cells. Its role in these cells is unknown. Here we tested the hypothesis that Islet-1+ cells retain proliferative activity and may therefore play a role in regenerating specialized regions in the heart. Methods and results: DNA synthesis was analyzed by the incorporation of tritiated thymidine (3H-thymidine) in Isl-1-nLacZ mice, a transgenic model with an insertion of a nuclear beta-galactosidase in the Islet-1 locus. Mice received daily injections of 3H-thymidine for 5 days. DNA synthesis was visualized throughout the heart by dipping autoradiography of cryosections. Colocalization of an nLacZ-signal and silver grains would indicate DNA synthesis in Islet-1+ cells. Whereas Islet− non-myocyte nuclei were regularly marked by accumulation of silver grains, colocalization with nLacZ-signals was not detected in >25,000 cells analyzed. Conclusions: Islet-1+ cells are quiescent in the adult heart, suggesting that, under normal conditions, even pacemaking cells do not proliferate at higher rates than normal cardiac myocytes.
    Biochemical and Biophysical Research Communications 11/2014;
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    ABSTRACT: In this study, we investigated the effects of the histone deacetylase inhibitor PXD101 (belinostat) on the preimplantation development of porcine somatic cell nuclear transfer (SCNT) embryos and their expression of the epigenetic markers histone H3 acetylated at lysine 9 (AcH3K9). We compared the in vitro developmental competence of SCNT embryos treated with various concentrations of PXD101 for 24 h. Treatment with 0.5 μM PXD101 significantly increased the proportion of SCNT embryos that reached the blastocyst stage, in comparison to the control group (23.3% vs. 11.5%, P < 0.05). We tested the in vitro developmental competence of SCNT embryos treated with 0.5 μM PXD101 for various amounts of times following activation. Treatment for 24 h significantly improved the development of porcine SCNT embryos, with a significantly higher proportion of embryos reaching the blastocyst stage in comparison to the control group (25.7% vs. 10.6%, P < 0.05). PXD101-treated SCNT embryos were transferred into two surrogate sows, one of whom became pregnant and four fetuses developed. PXD101 treatment significantly increased the fluorescence intensity of immunostaining for AcH3K9 in embryos at the pseudo-pronuclear and 2-cell stages. At these stages, the fluorescence intensities of immunostaining for AcH3K9 were significantly higher in PXD101-treated embryos than in control untreated embryos. In conclusion, this study demonstrates that PXD101 can significantly improve the in vitro and in vivo developmental competence of porcine SCNT embryos and can enhance their nuclear reprogramming.
    Biochemical and Biophysical Research Communications 11/2014;
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    ABSTRACT: Radiotherapy of is well established and frequently utilized in prostate cancer (PCa) patients. However, recurrence following therapy and distant metastases are commonly encountered problems. Previous studies underline that, in addition to its therapeutic effects, ionizing radiation (IR) increases the vascularity and invasiveness of surviving radioresistant cancer cells. This invasive phenotype of radioresistant cells is an upshot of IR-induced pro-survival and mitogenic signaling in cancer as well as endothelial cells. Here, we demonstrate that a plant flavonoid, silibinin can radiosensitize endothelial cells by inhibiting expression of pro-angiogenic factors. Combining silibinin with IR not only strongly down-regulated endothelial cell proliferation, clonogenicity and tube formation ability rather it strongly (p < 0.001) reduced migratory and invasive properties of PCa cells which were otherwise marginally affected by IR treatment alone. Most of the pro-angiogenic (VEGF, iNOS), migratory (MMP-2) and EMT promoting proteins (uPA, vimentin, N-cadherin) were up-regulated by IR in PCa cells. Interestingly, all of these invasive and EMT promoting actions of IR were markedly decreased by silibinin. Further, we found that potentiated effect was an end result of attenuation of IR-activated mitogenic and pro-survival signaling, including Akt, Erk1/2 and STAT-3, by silibinin.
    Biochemical and Biophysical Research Communications 11/2014;
  • Amanda K. Hare, Edward N. Harris
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    ABSTRACT: The hyaluronan receptor for endocytosis (HARE), or Stabilin-2, is the mammalian endocytic clearance receptor for HA, heparin, advanced glycation end-products, acetylated and oxidized low-density lipoproteins and collagen N-terminal propeptides. This large 2551 amino acid receptor is encoded by a gene that covers over 180 kbp on human chromosome 12 and is predicted to be composed of 69 exons. Due to the expression profile of this gene and the number of exons it contains, we hypothesized that splice variants of stab2 are encoded in these tissues. In addition, a correlation between alternative splice variants and cancer progression has been shown in other HA receptors such as RHAMM and CD42. In this study, two methods were utilized in identifying and/or isolating the HARE splice variants. The first method used primer sets to amplify the 190-HARE encoding region that could contain splice junctions; therefore, they could be removed from the gel, purified, and sequenced. Five splice variants were detected in that manner. In the second approach, the entire open reading frame of HARE was amplified. This allowed four splice variants with extensive exon splicing to be isolated. After the splice variants were sequenced, three were cloned into a mammalian expression vector. Next, stable cell lines expressing the variants were created in order to determine stable protein expression. In this study, the splice variants were found to be tissue specific in most cases. This means that tissue specific regulatory splicing mechanisms may lead to differences in functionality between the splice variants.
    Biochemical and Biophysical Research Communications 11/2014;
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    ABSTRACT: Hydrogen sulfide (H2S) is a gaseous regulatory factor produced by several enzymes, and plays a pivotal role in processes such as proliferation or vasodilation. Recent reports demonstrated the physiological and pathophysiological functions of H2S in neurons. PTEN is a target of nitric oxide (NO) or hydrogen peroxide, and the oxidative modification of cysteine (Cys) residue(s) attenuates its enzymatic activity. In the present study, we assessed the effect of H2S on the direct modification of PTEN and the resulting downstream signaling. A modified biotin switch assay in SH-SY5Y human neuroblastoma cells revealed that PTEN is S-sulfhydrated endogenously. Subsequently, site-directed mutagenesis demonstrated that both Cys71 and Cys124 in PTEN are targets for S-sulfhydration. Further, the knockdown of cystathionine β-synthetase (CBS) using siRNA decreased this modification in a manner that was correlated to amount of H2S. PTEN was more sensitive to NO under these conditions. These results suggest that the endogenous S-sulfhydration of PTEN via CBS/H2S plays a role in preventing the S-nitrosylation that would inhibition its enzymatic activity under physiological conditions.
    Biochemical and Biophysical Research Communications 11/2014;
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    ABSTRACT: Forkhead transcription factors are essential for diverse processes in early embryonic development and organogenesis. As a member of the forkhead family, FOXD1 is required during kidney development and its inactivation results in failure of nephron progenitor cells. However, the role of FOXD1 in carcinogenesis and progression is still limited. Here, we reported that FOXD1 is a potential oncogene in breast cancer. We found that FOXD1 is up-regulated in breast cancer tissues. Depletion of FOXD1 expression decreases the ability of cell proliferation and chemoresistance in MDA-MB-231 cells, whereas overexpression of FOXD1 increasesthe ability of cell proliferation and chemoresistance in MCF-7 cells. Furthermore, we observed that FOXD1 induces G1 to S phase transition by targeting p27 expression. Our results suggest that FOXD1 may be a potential therapy target for patients with breast cancer.
    Biochemical and Biophysical Research Communications 11/2014;
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    ABSTRACT: microRNAs (miRNAs) are short (19–24 nt), low molecular weight RNAs that play important roles in the regulation of target genes associated with cell proliferation, differentiation, and development, by binding to the 3′-untranslated region of the target mRNAs. In this study, we examined the expression of miRNA-126 (miR-126) and miR-149 in prostate cancer, and investigated the molecular mechanisms by which they affect syndecan-1 in prostate cancer. Functional analysis of miR-126 and miR-149 was conducted in the prostate cancer cell lines, PC3, Du145, and LNCaP. The expression levels of SOX2, NANOG, Oct4, miR-126 and miR-149 were evaluated by quantitative RT-PCR. After silencing syndecan-1, miR-126, and/or miR-149 in the PC3 cells, cell proliferation, senescence, and p21 induction were assessed using the MTS assay, senescence-associated β-galactosidase (SA-β-Gal) assay, and immunocytochemistry, respectively. Compared to the Du145 and LNCaP cells, PC3 cells exhibited higher expression of syndecan-1. When syndecan-1 was silenced, the PC3 cells showed reduced expression of miR-126 and miR-149 most effectively. Suppression of miR-126 and/or miR-149 significantly inhibited cell growth via p21 induction and subsequently, induced senescence. The mRNA expression levels of SOX2, NANOG, and Oct4 were significantly increased in response to the silencing of miR-126 and/or miR-149. Our results suggest that miR-126 and miR-149 are associated with the expression of syndecan-1 in prostate cancer cells. These miRNAs promote cell proliferation by suppressing SOX2, NANOG, and Oct4. The regulation of these factors by miR-126 and miR-149 is essential for syndecan-1-mediated development of androgen-refractory prostate cancer.
    Biochemical and Biophysical Research Communications 11/2014;
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    ABSTRACT: Interferon (IFN) is a key component of the innate immune response to exogenous pathogens. Interferon increases the mRNA levels of interferon-stimulated genes (ISGs) in vivo, which is thought to account for its antiviral activity. Recent studies have indicated that human myxovirus resistance protein 2 (Mx2 or MxB), one of these ISGs, contributes to the inhibition of HIV-1 replication by interferon. MxB may bind to HIV-1 relatively late in the post-entry phase, and it leads to a reduced level of integrated viral DNA, thereby restricting HIV-1 infection. The N-terminal 91-aa domain of MxB and the assembly of MxB mediated by the Stalk domain have also been shown to be indispensible for MxB’s anti-viral functions, but the mechanism involved has remained elusive. Here, we report the crystal structure (2.9 Å) of the human MxB Stalk domain. MxB Stalk shows one dimer in the asymmetric unit. Each monomer contains a four-helix bundle. Interestingly, analyses of MxB dimer interfaces show that the majority of residues involved in the interface are not conserved between MxB and MxA, contributing to the building of a more stable MxB dimer. MxA and MxB Stalk domains share 46.7% sequence identity, and the structure of the MxA Stalk domain and the overall structure of MxB Stalk have a similar conformation. Our results indicate that although human Mx proteins share common structural characteristics, their dimerization strategies are unique, contributing to their unique contributions to viral restriction.
    Biochemical and Biophysical Research Communications 11/2014;
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    ABSTRACT: A key event in the progression of systemic inflammation resulting from severe trauma or shock involves microvascular hyperpermeability, which leads to excessive plasma fluid and proteins accumulating in extravascular space resulting in tissue edema. The precise molecular mechanism of the hyperpermeability response is not completely understood. Protein tyrosine kinase 6 (PTK6, also known as breast tumor kinase BRK) is a non-receptor tyrosine kinase related to Src-family proteins. Although it has also been shown that PTK6 participates in regulating epithelial barrier function, the role of PTK6 in endothelial barrier function has not been reported. In this study, we hypothesized that PTK6 is (1) expressed in vascular endothelial cells, and (2) contributes to vascular endothelial hyperpermeability in response to TNFα. Results showed that PTK6 was detected in mouse endothelial cells at the level of protein and mRNA. In addition, PTK6 knockdown attenuated TNFα induced decrease in endothelial barrier function as measured by electric cell-substrate impedance sensing (ECIS) and in vitro transwell albumin-flux assays. Furthermore, we showed that TNFα treatment of endothelial cells increased active PTK6 association with p120-catenin at endothelial cell–cell junctions. Further analysis using immunocytochemistry and immunoprecipitation demonstrated that PTK6 knockdown attenuated TNFα induced VE-cadherin internalization as well as promoting its association with p120-catenin. Our study demonstrates a novel role of PTK6 in mediating endothelial barrier dysfunction.
    Biochemical and Biophysical Research Communications 11/2014;
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    ABSTRACT: The purpose of this study was to investigate the relationship between huntingtin-associated protein1 (HAP1) gene and radiation therapy of breast cancer cells.MethodsHAP1 gene was transfected into breast cancer MCF-7 cells, which was confirmed by quantitative reverse transcription-polymerase chain reaction analysis (qRT-PCR) and Western blot in vitro. The changes of cell radiosensitivity were assessed by colony formation assay. Apoptosis were examined by flow cytometry. The expressions of two radiation-induced genes were evaluated by Western blot. Tumor growth was investigated in nude mice xenograft models in vivo.ResultsOur data showed that HAP1 gene expression was significantly increased in HAP1-transfected MCF-7 cells in comparison with the parental cells or negative control cells. The survival rate in MCF-7/HAP1 cells was significantly decreased after irradiation (0, 2, 4, 6, 8 Gy), compared to cells in MCF-7 and MCF-7/Pb groups in vitro. HAP1 gene increased apoptosis in MCF-7 cells after irradiation. Additionally, the tumor volume and weight in MCF-7/HAP1 + RT group were observably lower than in MCF-7/HAP1 group and MCF-7/Pb + RT group.Conclusion The present study indicated that HAP1 gene expression was related to the radiosensitivity of breast cancer cells and may play an important role in the regulation of cellular radiosensitivity.
    Biochemical and Biophysical Research Communications 11/2014;
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    ABSTRACT: The development of severe immunodeficient mouse strains containing various human genes, including cytokines or HLA, has enabled the reconstitution of functional human immune systems after transplantation of human hematopoietic stem cells (HSC). Accumulating evidence has suggested that HLA-restricted antigen-specific human T-cell responses can be generated in these humanized mice. To directly monitor immune responses of human CD4+ T cells, we introduced β-lactoglobulin (BLG)-specific T cell receptor (TCR) genes derived from CD4+ T-cell clones of cow-milk allergy patients into HSCs, and subsequently transplanted them into NOG-HLA-DR4 transgenic / I-Aβ deficient mice (NOG-DR4/I-Ao). In the thymus, thymocytes with BLG-specific TCR preferentially differentiated into CD4+CD8- single-positive cells. Adoptive transfer of mature CD4+ T cells expressing the TCR into recipient NOG-DR4/I-Ao mice demonstrated that human CD4+ T cells proliferated in response to antigenic stimulation and produced IFN-γ in vivo, suggesting that functional T-cell reactions (especially Th1-skewed responses) were induced in humanized mice.
    Biochemical and Biophysical Research Communications 11/2014;
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    ABSTRACT: Previous studies showed that certain regions of Escherichiacoli SecA can be deleted from its N- and/or C-termini to complement a SecA amber ts mutant. In this study, we determined and characterized the dispensability of both ends of SecA molecules. With N-terminal intact or 9-aa deleted, 826aa (SecA1–826 and SecA10–826, respectively) is the minimum for complementation activity, while with N-terminus deleted by 2–21aa, SecA22–829 is the minimum. Further deletion at the C-terminus of SecA1–826/SecA10–826/SecA22–829 abolished the complementation activity in the cells. A hydrophobic amino acid is required for the 826th residue in the minimal-length SecAs. Chemical crosslinking and gel filtration result showed that both purified SecA22–828 and SecA22–829 could form a dimer. Moreover, the in vitro ATPase and protein translocation activities of SecA22–828 and SecA22–829 were similar, though lower than wild-type SecA. The active mutants had more truncated SecA in soluble than membrane-bound form, but was more stably embedded in membranes. In contrast, the inactive mutants tended to have truncated SecA more membrane-bound than soluble form, and were more loosely bound and easily chased out. Thus, the loss of complementation appears to be related to their altered subcellular localization and stability in the membranes. This study defines the substantial regions of N- and C-termini of SecA that may be deleted without losing complementation activity.
    Biochemical and Biophysical Research Communications 11/2014;
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    ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease. An evidence-based pharmacological treatment for NAFLD is still lacking, but flavonoids have shown therapeutic potential. The present study was designed to investigate the effect of the flavonoid monoHER on the onset of NAFLD in Ldlr-/- mice on a high-fat and high-cholesterol diet. The focus was put on the effect on oxidative stress as well as the adaptive response. Wild type mice served as a control and the effect of monoHER was compared to that of a placebo.In the Ldlr-/- group, monoHER provided only a mild protection against oxidative stress. In the placebo Ldlr-/- group an adaptive response elicited by the NRF2 antioxidant defense system was observed, evidenced by a higher HO-1 and Gpx3 gene expression, as well as an increased redox status, evidenced by the higher GSH/GSSG ratio. In the monoHER treated Ldlr-/- group both the adaptive response as well as the increase in redox status tended to be higher, although this did not reach significance on a group level. Unexpectedly, a strong within animal relationship was found that links a high adaptive response to a low redox status in the monoHER Ldlr-/- group. This correlation was absent in the placebo and wildtype group.The concept that emerges is that a thiol-reactive oxidation product of monoHER, formed during oxidative stress, selectively induces the NRF2 pathway and enforces the endogenous antioxidant shield, to provide protection against NAFLD.
    Biochemical and Biophysical Research Communications 11/2014;
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    ABSTRACT: Fibroblast growth factors (FGFs) are a family of structurally related heparin-binding proteins with diverse biological functions. FGFs participate in mitogenesis, angiogenesis, cell proliferation, development, differentiation and cell migration. Here, we investigated the potential effect of FGF10, a member of FGFs, on neuron survival in oxygen–glucose deprivation (OGD) model. In primary cultured mouse cortical neurons upon OGD, FGF10 treatment (100 and 1000 ng/ml) attenuated the decrease of cell viability and rescued the LDH release. Tuj-1 immunocytochemistry assay showed that FGF10 promoted neuronal survival. Apoptosis assay with Annexin V + PI by flow cytometry demonstrated that FGF10 treatment reduced apoptotic cell proportion. Moreover, immunoblotting showed that FGF10 alleviated the cleaved caspase-3 upregulation caused by OGD. FGF10 treatment also depressed the OGD-induced increase of caspase-3, -8 and -9 activities. At last, we found FGF10 triggered heme oxygenase-1 (HO-1) protein expression rather than hypoxia-inducible factor-1 (HIF-1), AMP-activated protein kinase (AMPK) signaling and extracellular signal-regulated kinases 1/2 (ERK1/2) signaling. Knockdown of HO-1 by siRNA partly abolished the neuroprotection of FGF10 in OGD model. In summary, our observations provide the first evidence for the neuroprotective function of FGF10 against ischemic neuronal injury and suggest that FGF10 may be a promising agent for treatment of ischemic stroke.
    Biochemical and Biophysical Research Communications 11/2014;
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    ABSTRACT: Dynamin-related proteins (DRPs) are large GTPases involved in a wide range of cellular membrane remodeling processes. In Arabidopsis thaliana, two paralogous land plant-specific type DRPs, DRP2A and DRP2B, are thought to participate in the regulation of post-Golgi trafficking. Here, we examined their molecular properties and functional relationships. qRT-PCR and GUS assays showed that DRP2A and DRP2B were expressed ubiquitously, although their expressions were strongest around root apical meristems and vascular bundles. Yeast two-hybrid, bi-molecular fluorescent complementation, and co-immunoprecipitation mass spectrometry analyses revealed that DRP2A and DRP2B interacted with each other. In observations with confocal laser scanning microscopy and variable incidence angle fluorescent microscopy, fluorescent fusions of DRP2A and DRP2B almost completely co-localized and were mainly localized to endocytic vesicle formation sites of the plasma membrane, clathrin-enriched trans-Golgi network and the cell plate in root epidermal cells. Treatments with wortmannin, an inhibitor of phosphatidylinositol 3-/4-kinases, latrunculin B, an inhibitor of actin polymerization, and oryzalin, an inhibitor of microtubule polymerization, increased the resident time of DRP2A and DRP2B on the plasma membrane. These results show that DRP2A and DRP2B function coordinately in multiple pathways of post-Golgi trafficking in phosphatidylinositol 3- or 4-kinase and cytoskeleton polymerization-dependent manners.
    Biochemical and Biophysical Research Communications 11/2014;