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Göbel R 《Mycotoxin Research》2001,17(2):210-213
A method for the combined determination of the mycotoxins aflatoxin B1, G1, B2, G2, ochratoxin A and zearalenone in cereals and feed is described. After extraction with acetonitrile/water or methanol/water the cleaning takes place with new combined immunoaffinity clean-up column “AflaOchraZea” by VICAM. When the mycotoxins are determined in different cereals with this new type of clean-up column low detection limits and high recovery rates can be reached similar to those obtained by using separate immunoaffinity clean-up colums for the said mycotoxins. 相似文献
3.
We previously reported that Gd-containing particles formed under physiological conditions act as active entities to enhance
cell survival and promote S phase entry via activation of both mitogen-activated protein kinase/extracellular-signal-regulated
protein kinase (ERK) and phosphatidylinositol 3-kinase/Akt signaling pathways. However, how they transduce the extracellular
signal inside the cell remains unclear. The present study demonstrates that Gd-containing particles can alleviate serum-deprivation-induced
cell death and promote G1 to S phase cell cycle progression by enhancing cell adhesion to the extracellular matrix. As an indicator of adhesion, the
vinculin distribution was detected by confocal laser scanning microscopy. The control cells exhibited fewer and less typical
focal adhesions. After treatment with Gd-containing particles, a large number of vinculin-containing focal adhesions were
maintained. In the presence of integrin antagonists, the percentage of S phase entry induced by Gd-containing particles was
decreased and the enhancement of cell viability was also attenuated, along with a decrease in both cyclin D expression and
ERK phosphorylation. In summary, the present results suggest that the integrin-mediated signaling pathway plays an important
role in cell survival and G1 to S phase transition promoted by Gd-containing particles by enhancing focal adhesion formation. The results presented here
provide novel evidence to advance knowledge leading to further understanding of the mechanisms of both cell proliferation
and cell survival promoted by Gd and may be helpful for developing effective measures to prevent or treat nephrogenic systemic
fibrosis. 相似文献
4.
Christine Bonnesen Gitte-Mai Nelander Bo Falck Hansen Pia Jensen Jonas S. Krabbe Marianne B. Jensen Anne Charlotte Hegelund Jette E. Svendsen Martin B. Oleksiewicz 《Cell biology and toxicology》2010,26(4):293-307
Evaluating mitogenic signaling specifically through the human insulin receptor (IR) is relevant for the preclinical safety
assessment of developmental insulin analogs. It is known that overexpression of IR sensitizes cells to the mitogenic effects
of insulin, but it is essentially unknown how mitogenic responses can be optimized to allow practical use of such recombinant
cell lines for preclinical safety testing. We constitutively overexpressed the short isoform of the human insulin receptor
(hIR-A, exon 11-negative) in L6 rat skeletal myoblasts. Because the mitogenic effect of growth factors such as insulin is
expected to act in G0/G1, promoting S-phase entry, we developed a combined topoinhibition + serum deprivation strategy to
explore the effect of G0/G1 synchronization as an independent parameter in the context of serum deprivation, the latter being
routinely used to reduce background in mitogenicity assays. G0/G1 synchronization significantly improved the mitogenic responses
of L6-hIR cells to insulin, measured by 3H-thymidine incorporation. Comparison with the parental L6 cells using phospho-mitogen-activated protein kinase, phospho-AKT,
as well as 3H-thymidine incorporation end points supported that the majority of the mitogenic effect of insulin in L6-hIR cells was mediated
by the overexpressed hIR-A. Using the optimized L6-hIR assay, we found that the X-10 insulin analog was more mitogenic than
native human insulin, supporting that X-10 exhibits increased mitogenic signaling through the hIR-A. In summary, this study
provides the first demonstration that serum deprivation may not be sufficient, and G0/G1 synchronization may be required to
obtain optimal responsiveness of hIR-overexpressing cell lines for preclinical safety testing. 相似文献
5.
Background
Mitochondria exhibit a dynamic morphology in cells and their biogenesis and function are integrated with the nuclear cell cycle. In mitotic cells, the filamentous network structure of mitochondria takes on a fragmented form. To date, however, whether mitochondrial fusion activity is regulated in mitosis has yet to be elucidated.Findings
Here, we report that mitochondria were found to be fragmented in G2 phase prior to mitotic entry. Mitofusin 1 (Mfn1), a mitochondrial fusion protein, interacted with cyclin B1, and their interactions became stronger in G2/M phase. In addition, MARCH5, a mitochondrial E3 ubiquitin ligase, reduced Mfn1 levels and the MARCH5-mediated Mfn1 ubiquitylation were enhanced in G2/M phase.Conclusions
Mfn1 is degraded through the MARCH5-mediated ubiquitylation in G2/M phase and the cell cycle-dependent degradation of Mfn1 could be facilitated by interaction with cyclin B1/Cdk1 complexes.6.
Background
Polyamines and ornithine decarboxylase (ODC) are essential for cell proliferation. DL-α-difluoromethylornithine (DFMO), a synthetic inhibitor of ODC, induces G1 arrest through dephosphorylation of retinoblastoma protein (pRb). The effect of DFMO on cell growth of pRb deficient cells is not known. We examined the effects of DFMO on pRb deficient human retinoblastoma Y79 cell proliferation and its molecular mechanism. 相似文献7.
Jing Fang Heng Yin Zhixiang Zheng Panpan Zhu Xi Peng Zhicai Zuo Hengmin Cui Yi Zhou Ping Ouyang Yi Geng Junliang Deng 《Biological trace element research》2018,181(1):142-153
Aflatoxin B1 (AFB1) is the most toxic among the mycotoxins and causes detrimental health effects on human and animals. Selenium (Se) plays an important role in chemopreventive, antioxidant, anticarcinogen, and detoxification and involved in cell cycle regulation. The aim of this study was to explore the molecular mechanisms of selenium involved in inhibition of G2/M cell cycle arrest of broiler’s jejunum. A total of 240 one-day-old healthy Cobb broilers were randomly divided into four groups and fed with basal diet (control group), 0.6 mg/kg AFB1 (AFB1 group), 0.4 mg/kg Se (+Se group), and 0.6 mg/kg AFB1 + 0.4 mg/kg Se (AFB1 + Se group) for 21 days, respectively. The histological observation and morphological analysis revealed that 0.4 mg/kg Se prevented the AFB1-associated lesions of jejunum including the shedding of the apical region of villi, the decreased villus height, and villus height/crypt ratio. The cell cycle analysis by flow cytometry showed that 0.4 mg/kg Se ameliorated the AFB1-induced G2/M phase arrest in jejunal cells. Moreover, the expressions of ATM, Chk2, p53, Mdm2, p21, PCNA, Cdc25, cyclin B, and Cdc2 analyzed by immunohistochemistry and qRT-PCR demonstrated that 0.4 mg/kg Se restored these parameters to be close to those in the control group. In conclusion, Se promoted cell cycle recovery from the AFB1-induced G2/M phase arrest by the molecular regulation of ATM pathway in the jejunum of broilers. The outcomes from the present study may lead to a better understanding of the nature of selenium’s essentiality and its protective roles against AFB1. 相似文献
8.
We examined, in vitro, whether hyaluronan induces slow cycling in placenta-derived mesenchymal stem cells (PDMSCs) by comparing
cell growth on a hyaluronan-coated surface with cell growth on a tissue-culture polystyrene surface. The hyaluronan-coated
surface significantly downregulated the proliferation of PDMSCs, more of which were maintained in the G0/G1 phases than were cells on the tissue-culture polystyrene surface. Both PKH-26 labeling and BrdU incorporation assays showed
that most PDMSCs grown on a hyaluronan-coated surface duplicated during cultivation indicating that the hyaluronan-coated
surface did not inhibit PDMSCs from entering the cell cycle. Mitotic synchronization showed that the G1-phase transit was prolonged in PDMSCs growing on a hyaluronan-coated surface. Increases in p27Kip1 and p130 were the crucial factors that allowed hyaluronan to lengthen the G1 phase. Thus, hyaluronan might be a promising candidate for maintaining stem cells in slow-cycling mode by prolonging their
G1-phase transit.
This work was supported by research grant NSC95-2745-B-006-003-MY2 from the National Science Council, Taiwan, and by Landmark
Project Grant A25, funded by the Taiwan Ministry of Education, from National Cheng Kung University. 相似文献
9.
10.
Jipeng Li Yulan Song Yiping Wang Jianping Luo Wanjun Yu 《Molecular and cellular biochemistry》2013,380(1-2):277-282
Recent studies have implied that miRNAs act as crucial modulators for epithelial-to-mesenchymal transition (EMT). We found that miR-148a is significantly downregulated in non-small cell lung cancer (NSCLC) compared to adjacent non-cancerous lung tissues, and the downregulated miR-148a was significantly associated with lymph-node metastasis. Functional assays demonstrated that miR-148a inhibited EMT in NSCLC cells. Moreover, miR-148a decreased 3′-untranslated region luciferase activity of ROCK1 and ROCK1 protein expression. Knockdown of ROCK1 reversed EMT resembling that of miR-148a overexpression. Furthermore, ROCK1 was widely upregulated in NSCLC, and its mRNA levels were inversely correlated with miR-148a expression. These findings suggest that miR-148a acts as a novel EMT suppressor in NSCLC cells, at least in part by modulation of ROCK1. 相似文献
11.
Silvia Ravera Isabella Panfoli Maria Grazia Aluigi Daniela Calzia Alessandro Morelli 《Cell biochemistry and biophysics》2011,59(2):63-70
FoF1-ATP synthase is the nanomotor responsible for most of ATP synthesis in the cell. In physiological conditions, it carries
out ATP synthesis thanks to a proton gradient generated by the respiratory chain in the inner mitochondrial membrane. We previously
reported that isolated myelin vesicles (IMV) contain functional FoF1-ATP synthase and respiratory chain complexes and are able to conduct an aerobic metabolism, to support the axonal energy
demand. In this study, by biochemical assay, Western Blot (WB) analysis and immunofluorescence microscopy, we characterized
the IMV FoF1-ATP synthase. ATP synthase activity decreased in the presence of the specific inhibitors (olygomicin, DCCD, FCCP, valynomicin/nigericin)
and respiratory chain inhibitors (antimycin A, KCN), suggesting a coupling of oxygen consumption and ATP synthesis. ATPase
activity was inhibited in low pH conditions. WB and microscopy analyses of both IMV and optic nerves showed that the Inhibitor
of F1 (IF1), a small protein that binds the F1 moiety in low pH when of oxygen supply is impaired, is expressed in myelin sheath. Data are discussed in terms of the role
of IF1 in the prevention of the reversal of ATP synthase in myelin sheath during central nervous system ischemic events. Overall,
data are consistent with an energetic role of myelin sheath, and may shed light on the relationship among demyelination and
axonal degeneration. 相似文献
12.
Xiaoyan Li Yanli Zeng XueYing Zhang Shijun Zheng Lingpeng Meng 《Journal of molecular modeling》2011,17(4):757-767
The nature of the lithium/hydrogen bonding between (CH2)2X(X: C=CH2, O, S) and LiY/HY(Y=F, Cl, Br) have been theoretically investigated at MP2/6-311++G (d, p) level, using Bader’s “atoms in
molecules (AIM)” theory and Weinhold’s “natural bond orbital (NBO)” methodology. The molecule formation density differences
(MFDD) of the titled complexes are analyzed. Two kinds of geometries of the lithium/hydrogen bonded complexes are compared.
As a whole, the nature of lithium bond and hydrogen bond are different. For the same electron donor and the same acceptor,
lithium bond is stronger than hydrogen bond. For the same electron acceptor and different kind of donors, the interaction
energies follows the n-type> π-type > pseudo-π-type order. For the same (CH2)2X, the interaction energy increases in the sequence of Y=F, Cl and Br for lithium bond systems while it decreases for hydrogen
bond systems. Electron transfer plays an important role in the formation of lithium bond systems while it is less important
in the hydrogen bond systems. 相似文献
13.
The COX-2 product prostaglandin E2 (PGE2) contributes to the high metastatic capacity of breast tumors. Our published data indicate that inhibiting either PGE2 production or PGE2-mediated signaling through the PGE2 receptor EP4 reduces metastasis by a mechanism that requires natural killer (NK) cells. It is known that NK cell function
is compromised by PGE2, but very little is known about the mechanism by which PGE2 affects NK effector activity. We now report the direct effects of PGE2 on the NK cell. Endogenous murine splenic NK cells express all four PGE2 receptors (EP1-4). We examined the role of EP receptors in three NK cell functions: migration, cytotoxicity, and cytokine
release. Like PGE2, the EP4 agonist PGE1-OH blocked NK cell migration to FBS and to four chemokines (ITAC, MIP-1α, SDF-1α, and CCL21). The EP2 agonist, Butaprost,
inhibited migration to specific chemokines but not in response to FBS. In contrast to the inhibitory actions of PGE2, the EP1/EP3 agonist Sulprostone increased migration. Unlike the opposing effects of EP4 vs. EP1/EP3 on migration, agonists
of each EP receptor were uniformly inhibiting to NK-mediated cytotoxicity. The EP4 agonist, PGE1-OH, inhibited IFNγ production from NK cells. Agonists for EP1, EP2, and EP3 were not as effective at inhibiting IFNγ. Agonists
of EP1, EP2, and EP4 all inhibited TNFα; EP4 agonists were the most potent. Thus, the EP4 receptor consistently contributed
to loss of function. These results, taken together, support a mechanism whereby inhibiting PGE2 production or preventing signaling through the EP4 receptor may prevent suppression of NK functions that are critical to
the control of breast cancer metastasis. 相似文献
14.
Stuart Hunt Adam V. Jones Emma E. Hinsley Simon A. Whawell Daniel W. Lambert 《FEBS letters》2011,585(1):187
Alterations in the levels of molecules which interact with the extracellular matrix, such as integrins, are associated with invasion of oral squamous cell carcinomas (OSCC). The molecular mechanisms underlying dysregulation of integrin expression in OSCC, however, remain unclear. Here, we show that microRNA-124, a small non-coding RNA down-regulated in OSCC, is able to downregulate expression of integrin beta-1 (ITGB1) by interacting with its 3′ untranslated region. Over-expression of miR-124 attenuates endogenous ITGB1 expression and reduces the adherence and motility of OSCC cells, suggesting disruption of miR-124-mediated repression of ITGB1 may be a key factor in OSCC progression. 相似文献
15.
Jeon Y Lee KY Ko MJ Lee YS Kang S Hwang DS 《The Journal of biological chemistry》2007,282(20):14882-14890
Human TopBP1 with eight BRCA1 C terminus domains has been mainly reported to be involved in DNA damage response pathways. Here we show that TopBP1 is also required for G(1) to S progression in a normal cell cycle. TopBP1 deficiency inhibited cells from entering S phase by up-regulating p21 and p27, resulting in down-regulation of cyclin E/CDK2. Although co-depletion of p21 and p27 with TopBP1 restored the cyclin E/CDK2 kinase activity, however, cells remained arrested at the G(1)/S boundary, showing defective chromatin-loading of replication components. Based on these results, we suggest a dual role of TopBP1 necessary for the G(1)/S transition: one for activating cyclin E/CDK2 kinase and the other for loading replication components onto chromatin to initiate DNA synthesis. 相似文献
16.
Boisbouvier J Bryce DL O'neil-Cabello E Nikonowicz EP Bax A 《Journal of biomolecular NMR》2004,30(3):287-301
New methods are described for accurate measurement of multiple residual dipolar couplings in nucleic acid bases. The methods use TROSY-type pulse sequences for optimizing resolution and sensitivity, and rely on the E.COSY principle to measure the relatively small two-bond 2DCH couplings at high precision. Measurements are demonstrated for a 24-nt stem-loop RNA sequence, uniformly enriched in 13C, and aligned in Pf1. The recently described pseudo-3D method is used to provide homonuclear 1H-1H decoupling, which minimizes cross-correlation effects and optimizes resolution. Up to seven 1H-13C and 13C-13C couplings are measured for pyrimidines (U and C), including 1DC5H5, 1DC6H6, 2DC5H6, 2DC6H5, 1DC5C4, 1DC5C6, and 2DC4H5. For adenine, four base couplings (1DC2H2, 1DC8H8, 1DC4C5, and 1DC5C6) are readily measured whereas for guanine only three couplings are accessible at high relative accuracy (1DC8H8, 1DC4C5, and 1DC5C6). Only three dipolar couplings are linearly independent in planar structures such as nucleic acid bases, permitting cross validation of the data and evaluation of their accuracies. For the vast majority of dipolar couplings, the error is found to be less than ±3% of their possible range, indicating that the measurement accuracy is not limiting when using these couplings as restraints in structure calculations. Reported isotropic values of the one- and two-bond J couplings cluster very tightly for each type of nucleotide. 相似文献
17.
Dapeng Wang Fuqin Bao Yugang Teng Qiang Li 《Bioscience, biotechnology, and biochemistry》2019,83(5):836-844
Osteosarcoma (OS) is the most common malignant bone tumor. In cancer cells, autophagy is related to epithelial-to-mesenchymal transition (EMT). Although microRNA (miR)-506-3p has been demonstrated to act as a tumor suppressor in OS, its role in regulating the EMT process and autophagy remains unknown. The results showed that miR-506-3p directly inhibited the expression of sphingosine kinase 1 (SPHK1) in 143B and SaOS-2 cells. The invasive capability of OS cells was reduced following miR-506-3p mimics transfection, and restored when SPHK1 was overexpressed simultaneously. Further, miR-506-3p mimics initiated mesenchymal-to-epithelial transition (MET) – E-cadherin expression was upregulated, whilst vimentin and fibronectin were downregulated. The basal autophagy flux (LC3II/I) was suppressed by miR-506-3p mimics. The alterations induced by miR-506-3p mimics were partly reversed by SPHK1 overexpression or treatment of rapamycin. Meanwhile, treatment of SPHK1-transfected cells with 3-methyladenine inhibited EMT. The data suggest that miR-506-3p initiates MET and suppresses autophagy in OS cells by targeting SPHK1. 相似文献
18.
Carboxypeptidase G2 (CPG2) is a zinc-metalloenzyme employed in a range of cancer chemotherapy strategies by activating selectively nontoxic prodrugs
into cytotoxic drugs in tumor as well as in the treatment of intoxication caused by high-doses of the anticancer drug methotrexate
(MTX). CPG2 catalyzes the hydrolytic cleavage of C-terminal of glutamate moiety from folic acid and analogues. Regardless of its extensive
application, its mechanism of catalysis has not yet been determined and, so far, no co-crystallized complex has been published.
So, in this study, molecular docking and a short molecular dynamics (MD) simulation sampling scheme, as a function of temperature,
were performed to investigate a possible binding mode for MTX, a recognized substrate of CPG2. The findings suggested that MTX interacts possibly in quite specific points of the CPG2 active site, which are probably responsible for the molecular recognition and cleavage procedures. The MTX substrate fits
well in the catalytic site by accommodating the pteridine moiety in an adjacent pocket to the active site whereas a glutamate
moiety is pointed toward the protein surface. Additionally, a glutamate residue can interact with a crystallization water
molecule in the active site, supporting its activation as a nucleophilic group. 相似文献
19.
Genistein induces G<Subscript>2</Subscript>/M cell cycle arrest via stable activation of ERK1/2 pathway in MDA-MB-231 breast cancer cells 总被引:1,自引:0,他引:1
Genistein is an isoflavonoid present in soybeans that exhibits anti-carcinogenic effect. Several studies have shown that genistein can trigger G2/M cell cycle arrest and inhibit cell growth in human breast cancer cells. In the present study, we assessed the role of MEK-ERK cascade in regulation of genistein-mediated G2/M cell cycle arrest in the hormone-independent cell line MDA-MB-231. Flow cytometric analysis showed that treatment of MDA-MB-231 cells with genistein induced a concentration-dependent accumulation of cells in the G2/M phase of the cell cycle, with a parallel depletion of the percentage of cells in G0/G1. Genistein-mediated G2/M arrest was associated with a decrease in the protein levels of Cdk1, cyclinB1, and Cdc25C as determined by Western blot analysis. Genistein induced a slow and stable activation of phosphorylated ERK1/2 in a concentration- and time-dependent manner in MDA-MB-231 cells. MEK1/2-specific inhibitor PD98059 blocked genistein-induced activation of ERK1/2 and markedly attenuated genistein-induced G2/M arrest. Furthermore, genistein induced the expression of Ras and Raf-1 protein. Genistein also up-regulated steady-state levels of both c-Jun and c-Fos. PD98059 did not depress genistein-induced up-regulation of Ras and Raf-1 protein. However, it markedly blocked genistein-induced up-regulation of c-Jun and c-Fos. These results suggest that the Ras/MAPK/AP-1 signal pathway may be involved in genistein-induced G2/M cell cycle arrest in MDA-MB-231 breast cancer cells. 相似文献
20.
THE prostaglandins (PG) are possible mediators of inflammation. Prostaglandins E and F are present in inflammatory exudates1–3 and could be related to the increase of collagen biosynthesis associated with inflammation. Vane and his colleagues4–6 recently observed that indomethacin, aspirin and sodium salicylate potently block the biosynthesis of prostaglandins. These anti-inflammatory drugs are also inhibitors of collagen biosynthesis7,8. Morphological studies9 have revealed increased deposition of collagen or collagen-related elements in organ cultures of chick embryo skin containing prostaglandins E1 and B1. We report here results which indicate stimulation of collagen biosynthesis by prostaglandins E1 and F1α evaluated by hydroxylation of proline and lysine and glycosylation of hydroxylysine in 10 day chick embryo tibiae. 相似文献