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1.
Nat Mater ; 23(10): 1370-1378, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39026087

RESUMO

Iron-based 1111-type superconductors display high critical temperatures and relatively high critical current densities Jc. The typical approach to increasing Jc is to introduce defects to control dissipative vortex motion. However, when optimized, this approach is theoretically predicted to be limited to achieving a maximum Jc of only ∼30% of the depairing current density Jd, which depends on the coherence length and the penetration depth. Here we dramatically boost Jc in SmFeAsO1-xHx films using a thermodynamic approach aimed at increasing Jd and incorporating vortex pinning centres. Specifically, we reduce the penetration depth, coherence length and critical field anisotropy by increasing the carrier density through high electron doping using H substitution. Remarkably, the quadrupled Jd reaches 415 MA cm-2, a value comparable to cuprates. Finally, by introducing defects using proton irradiation, we obtain high Jc values in fields up to 25 T. We apply this method to other iron-based superconductors and achieve a similar enhancement of current densities.

2.
Zoolog Sci ; 40(1): 24-31, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36744707

RESUMO

DNA markers that detect differences in the number of microsatellite repeats can be highly effective for genotyping individuals that lack differences in external morphology. However, isolation of sequences with different microsatellite repeat numbers between individuals has been a time-consuming process in the development of DNA markers. Individual identification of Japanese giant flying squirrels (Petaurista leucogenys) has been challenging because this species is arboreal and nocturnal and exhibits little to no morphological variation between individuals. In this study, we developed DNA markers for sex and individual identification of this species by an efficient method using high-throughput DNA sequence data. Paired-end 5 Gb (2 × 250 bp) and 15 Gb (2 × 150 bp) genome sequences were determined from a female and a male Japanese giant flying squirrel, respectively. We searched SRY and XIST genes located on Y and X chromosomes, respectively, from high-throughput sequence data and designed primers to amplify these genes. Using these primer sets, we succeeded to identify the sex of individuals. In addition, we selected 12 loci containing microsatellites with different numbers of repeats between two individuals from the same data set, and designed primers to amplify these sequences. Twenty individuals from nine different locations were discriminated using these primer sets. Furthermore, both sex and microsatellite markers were amplified from DNA extracted non-invasively from single fecal pellet samples. Based on our results for flying squirrels, we expect our efficient method for developing non-invasive high-resolution individual- and sex-specific genotyping to be applicable to a diversity of mammalian species.


Assuntos
Genoma , Animais , Feminino , Humanos , Masculino , DNA , Marcadores Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Repetições de Microssatélites/genética , Sciuridae/genética
3.
J Chem Phys ; 152(12): 124708, 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32241116

RESUMO

X-ray absorption spectroscopy measurements were performed for the C K-edge of Pt nanoparticles on Ar+-irradiated carbon supports in order to elucidate the origin of improved catalyst performance after the introduction of vacancies into the carbon support. We observed a change in the electronic structure at the interface between the Pt nanoparticles and the carbon support after vacancy introduction, which is in good agreement with theoretical results. The results indicated that vacancy introduction resulted in a drastic change in the Pt-C interactions, which likely affected the d-band center of the Pt nanoparticles and led to the enhancement of the oxygen reduction reaction in catalysts.

4.
J Phys Condens Matter ; 32(14): 145501, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-31791023

RESUMO

CsBi4-x Pb x Te6 is synthesized and the superconductivity associated with the structural transition from Pb substitution is studied. Photoemission spectroscopy measurements are performed in order to elucidate the relationship between the electronic structure and the occurrence of the superconductivity. When Bi is substituted with Pb, an electron doping-like change in the electronic structure is directly observed which is contrary to the naive expectation of hole doping. This observation is consistent with band structure calculations and appears to be a unique characteristic of CsBi4-x Pb x Te6 because of the dissociation of Bi dimers upon Pb substitution. These results indicate that it may be possible to control the electron and hole doping via manipulating the Bi dimers through Pb substitution.

5.
J Synchrotron Radiat ; 25(Pt 5): 1444-1449, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30179184

RESUMO

For the purpose of imaging element- and shell-specific magnetic distributions under high magnetic fields, a scanning soft X-ray microscope has been developed at beamline BL25SU, SPring-8, Japan. The scanning X-ray microscope utilizes total electron yield detection of absorbed circularly polarized soft X-rays in order to observe magnetic domains through the X-ray magnetic circular dichroism effect. Crucially, this system is equipped with an 8 T superconducting magnet. The performance and features of the present system are demonstrated by magnetic domain observations of the fractured surface of a Nd14.0Fe79.7Cu0.1B6.2 sintered magnet.

6.
J Toxicol Sci ; 43(5): 321-327, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29743443

RESUMO

Bisphenol AF (BPAF) is now recognized as one of the replacements for bisphenol A (BPA). Although considerable experimental evidence suggests that BPA is an endocrine-disrupting chemical, the toxicological profile of BPAF has been investigated in less detail than that of BPA, even at the in vitro level. BPAF has been established as an activator of estrogen receptor α (ERα) in many cell lines; however, controversy surrounds its effects on the other isoform, ERß (i.e., whether it functions as a stimulator). Five human ERß isoforms have been cloned and characterized. Of these, we focused on the interactions between BPAF and the two isoforms, ERß1 and ERß2. We demonstrated that i) BPAF functioned as a stimulator of ERß1 (and ERα), which is transiently expressed in the two types of human breast cancer cells (MDA-MB-231 and SK-BR-3 cells) (EC50 values for ERß: 6.87 nM and 2.58 nM, respectively, and EC50 values for ERα: 24.7 nM and 181 nM, respectively), ii) the stimulation of ERß1 by BPAF (1-25 nM) was abrogated by PHTPP (an ERß selective antagonist), and iii) the expression of ERß1 and ERß2 was not modulated by BPAF at nanomolar concentrations up to 25 nM. These results indicate that BPAF activates not only human ERα, but also the ERß1 isoform in breast cancer cells, and exhibits higher activation potency for ERß1.


Assuntos
Compostos Benzidrílicos/toxicidade , Neoplasias da Mama/metabolismo , Disruptores Endócrinos/toxicidade , Receptor beta de Estrogênio/metabolismo , Fenóis/toxicidade , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Receptor beta de Estrogênio/genética , Feminino , Humanos , Isoformas de Proteínas/metabolismo , Transcrição Gênica/efeitos dos fármacos
7.
Biochem Biophys Res Commun ; 498(1): 86-91, 2018 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-29470987

RESUMO

One approach to increasing pharmacotherapy effects is administering drugs at times of day when they are most effective and/or best tolerated. Circadian variation in expression of pharmacokinetics- and pharmacodynamics-related genes was shown to contribute to dosing time-dependent differences in therapeutic effects of small molecule drugs. However, influence of dosing time of day on effects of high molecular weight formulations, such as drugs encapsulated in liposomes, has not been studied in detail. This study demonstrates that blood pressure rhythm affects dosing time-dependent variation in effects of high molecular weight formulations. Systolic blood pressure in sarcoma 180-bearing mice showed significant 24-h oscillation. Intratumoral accumulation of fluorescein isothiocyanate-labeled bovine serum albumin (FITC-BSA), an indicator of tumor vascular permeability, varied with dosing time of day, matching phases of blood pressure circadian rhythm. Furthermore, intratumoral accumulation of liposome-encapsulated oxaliplatin (Lipo-L-OHP) increased with increases in systolic blood pressure. Our findings suggest that circadian blood pressure oscillations may be an important factor to consider in dosing strategies for macromolecular drugs and liposomes in cancer therapy.


Assuntos
Angiotensina II/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Ritmo Circadiano/efeitos dos fármacos , Composição de Medicamentos , Substâncias Macromoleculares/metabolismo , Sarcoma/metabolismo , Animais , Permeabilidade Capilar/efeitos dos fármacos , Relação Dose-Resposta a Droga , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/metabolismo , Lipossomos , Masculino , Camundongos Endogâmicos ICR , Compostos Organoplatínicos/metabolismo , Oxaliplatina , Sarcoma/patologia , Soroalbumina Bovina/metabolismo , Sístole/efeitos dos fármacos , Fatores de Tempo
8.
Biol Pharm Bull ; 40(11): 1909-1916, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29093337

RESUMO

Bisphenols are endocrine disruptors that are widely found in the environment. Accumulating experimental evidence suggests an adverse interaction between bisphenols and estrogen signaling. Most studies have performed experiments that focused on estrogen receptor (ER) engagement by bisphenols. Therefore, the effects of bisphenols on the expression of ERα (ESR1) and ERß (ESR2) remain largely unknown. In the present study, we examined the effects of four bisphenols: bisphenol A (BPA), bisphenol B (BPB), bisphenol S (BPS), and bisphenol AF (BPAF), on estrogen signaling in two human breast cancer cell lines (MCF-7 and SK-BR-3). Among these bisphenols, BPAF up-regulated the expression of ERß, and this was coupled with the abrogation of estrogen response element (ERE)-mediated transcriptional activities as well as the down-regulation of Cdc2 expression in MCF-7 cells, without influencing the expression of ERα. BPAF functioned as an agonist of ERα at lower concentrations (nanomolar order), but did not exhibit any modulatory action on ERα transiently expressed in SK-BR-3 cells in the presence or absence of 17ß-estradiol (E2) at higher concentrations (micromolar order). The introduction of ERß cDNA resulted in greater reductions in MCF-7 cell viability than with BPAF alone. Since ERß is a suppressive molecule of ERα function, these results provide rational evidence for BPAF functioning as an anti-estrogenic compound via the induction of ERß at higher concentrations.


Assuntos
Compostos Benzidrílicos/farmacologia , Antagonistas de Estrogênios/farmacologia , Receptor beta de Estrogênio/metabolismo , Estrogênios/metabolismo , Fenóis/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteína Quinase CDC2/metabolismo , Relação Dose-Resposta a Droga , Regulação para Baixo , Disruptores Endócrinos/farmacologia , Estradiol/metabolismo , Receptor alfa de Estrogênio/agonistas , Receptor alfa de Estrogênio/metabolismo , Feminino , Humanos , Células MCF-7 , Elementos de Resposta/efeitos dos fármacos , Transcrição Gênica/efeitos dos fármacos , Regulação para Cima
9.
Cancer Res ; 77(23): 6603-6613, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29038345

RESUMO

Clock genes encoding transcription factors that regulate circadian rhythms may inform chronomodulated chemotherapy, where time-dependent dose alterations might affect drug efficacy and reduce side effects. For example, inhibiting the essential cystine transporter xCT with sulfasalazine induces growth arrest in cancer cells. Although the anticancer effects of sulfasalazine have been studied extensively, its effects on transcriptional control of xCT expression have not been studied. Here, we show that sulfasalazine administration during the period of increased xCT expression improves its anticancer effects and that the Clock gene itself induces xCT expression and regulates its circadian rhythm. Our findings highlight the clinical potential of chronomodulated chemotherapy and the importance of xCT-mediated transcriptional regulation in the utility of such strategies. Cancer Res; 77(23); 6603-13. ©2017 AACR.


Assuntos
Fatores de Transcrição ARNTL/genética , Sistema y+ de Transporte de Aminoácidos/antagonistas & inibidores , Antineoplásicos/farmacologia , Relógios Circadianos/fisiologia , Cronofarmacoterapia , Sulfassalazina/farmacologia , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação da Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Compostos Organoplatínicos/farmacologia , Oxaliplatina , Interferência de RNA , RNA Interferente Pequeno/genética , Transcrição Gênica/genética
10.
Biol Pharm Bull ; 40(8): 1192-1198, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28769000

RESUMO

Thiazolidinediones (TZDs) are known as peroxisome proliferator-activated receptor γ (PPARγ) activators, and are used in the treatment of diabetes. Although the usefulness of TZDs has been demonstrated, some of their side effects are becoming an obstacle to their clinical applicability; edema is known to be evoked by the "structural characteristics" of TZD, but not by the PPARγ activation. Thus, novel therapeutic modalities (i.e., non-TZD-type PPARγ activators) having different structures to those of TZDs are desired. We previously identified bongkrekic acid (BKA) as a PPARγ activator using the human breast cancer MCF-7 cell line as a model system. In the present study, we newly synthesized BKA analogs and examined the usefulness of BKA and its analogs as PPARγ activators in differentiated adipocyte cells. Among the chemicals investigated, one of the BKA analogs (BKA-#2) strongly stimulated PPARγ and the differentiation of 3T3-L1 cells similar to pioglitazone, a positive control. Furthermore, BKA-#2 reduced the size of lipid droplets in the mature adipocyte cells. The possible modulation mechanism by BKA-#2 is discussed.


Assuntos
Ácido Bongcréquico/análogos & derivados , Ácido Bongcréquico/farmacologia , PPAR gama/metabolismo , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Gotículas Lipídicas/efeitos dos fármacos , Camundongos
11.
J Toxicol Sci ; 42(4): 417-425, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28717100

RESUMO

Phthalate esters (PAEs) are man-made compounds that are used widely in industry, and the ubiquitous exposure of humans to PAEs has been reported. Although some PAEs have been suggested to function as xenoestrogens in in vitro systems, such as human estrogen receptors (ERs) expressed in Chinese hamster ovary (CHO)-K1 cells, few studies have attempted to elucidate whether PAEs affect human ERα/ERß-mediated signaling in human breast cancer cells (i.e., combination between human ERs and human cells). Thus, further experiments are needed in order to clarify the activities of PAEs. Among the 9 PAEs (carbon# in the side chains: 2-8) investigated, dibutyl phthalate (DBP), dipentyl phthalate (DPENP), and dicyclohexyl phthalate (DCHP) were found to exhibit strong anti-estrogenic activities in MCF-7 cells (ER-positive) in the presence of 1 nM 17ß-estradiol (E2). Since limited information is currently available on DPENP and DCHP, we herein focused on these two PAEs. Experiments using MDA-MB-231 cells (ER-negative) transfected with human ERα or ERß expression plasmids revealed that DCHP was a markedly stronger anti-estrogenic PAE than DPENP; DCHP inhibited ERα and ERß activities stimulated by 1 nM E2 with IC50 values of ~5 and 11.2 µM, respectively. Furthermore, DCHP abrogated diarylpropionitrile (DPN)-stimulated ERß activity with an IC50 value of 5.17 µM, which was approximately 2-fold stronger than that of DPENP (IC50 = 10 µM). The results of the present study suggest that PAEs (DCHP) function not only as an anti-estrogen for ERα, but also for ERß, at least in human breast cancer cell lines.


Assuntos
Neoplasias da Mama/metabolismo , Disruptores Endócrinos/toxicidade , Moduladores de Receptor Estrogênico , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Ácidos Ftálicos/toxicidade , Animais , Células CHO , Linhagem Celular Tumoral , Cricetinae , Cricetulus , Relação Dose-Resposta a Droga , Estradiol/farmacologia , Receptor alfa de Estrogênio/fisiologia , Receptor beta de Estrogênio/fisiologia , Feminino , Humanos , Células MCF-7 , Nitrilas/antagonistas & inibidores , Ácidos Ftálicos/química , Propionatos/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos
12.
J Nat Med ; 71(1): 286-291, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27530354

RESUMO

The physiological activities of cannabidiolic acid (CBDA), a component of fiber-type cannabis plants, have been demonstrated and include its function as a protector against external invasion by inducing cannabinoid-mediated necrosis (Shoyama et al., Plant Signal Behav 3:1111-1112, 2008). The biological activities of CBDA have been attracting increasing attention. We previously identified CBDA as an inhibitor of the migration of MDA-MB-231 cells, a widely used human breast cancer cell line in cancer biology, due to its highly aggressive nature. The chemical inhibition and down-regulation of cyclooxygenase-2 (COX-2), the expression of which has been detected in ~40 % of human invasive breast cancers, are suggested to be involved in the CBDA-mediated abrogation of cell migration. However, the molecular mechanism(s) responsible for the CBDA-induced down-regulation of COX-2 in MDA-MB-231 cells have not yet been elucidated. In the present study, we describe a possible mechanism by which CBDA abrogates the expression of COX-2 via the selective down-regulation of c-fos, one component of the activator protein-1 (AP-1) dimer complex, a transcription factor for the positive regulation of the COX-2 gene.


Assuntos
Neoplasias da Mama/genética , Canabinoides/química , Proteínas Proto-Oncogênicas c-fos/genética , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Movimento Celular , Regulação para Baixo , Feminino , Humanos , Invasividade Neoplásica
13.
Nat Prod Commun ; 12(5): 759-761, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-30496661

RESUMO

We reported that cannabidiolic acid (CBDA), a non-psychotropic constituent of fiber-type cannabis plants, down-regulates the mRNA expression of cyclooxygenase-2 (COX-2) in highly aggressive MDA-MB-231 human breast cancer cells. However, the molecular mechanism(s) underlying the CBDA suppression of COX-2 have not yet been elucidated in detail. In MDA-MB-231 cells, COX-2 expression is known to be tightly regulated by the transcriptional activity of activator protein-I (AP-1), which is composed of a heterodimer of c-Fos and c-Jun. AP-1-mediated transcriptional activity was inhibited by CBDA in a dose-dependent manner. The expression of c-fos was maintained at markedly lower levels (0.035) than basal c-jun expression levels (1.0), implicating c- fos as a limiting factor in the regulation of COX-2. Analyses indicated that CBDA abrogated the expression of c-fos mRNA without affecting c-jun. Collectively, these results suggest that CBDA abolishes the expression of COX-2 by interfering with AP-I activity in MDA-MB3-231 cells.


Assuntos
Neoplasias da Mama/metabolismo , Canabinoides/química , Canabinoides/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Fator de Transcrição AP-1/metabolismo , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Cannabis/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Estrutura Molecular , Folhas de Planta/química , Fator de Transcrição AP-1/genética
14.
Anticancer Res ; 36(10): 5171-5182, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27798877

RESUMO

BACKGROUND/AIM: An in vitro cell model of long-term estrogen-deprived MCF-7 (LTED) cells has been utilized to analyze the re-growth mechanisms of breast cancers treated with blockers for estrogen receptor α (ERα) signaling. Bongkrekic acid (BKA) is a natural toxin isolated from coconut tempeh contaminated with the bacterium Burkholderia cocovenans. MATERIALS AND METHODS: LTED cells, MCF-7 cells and MDA-MB-231 cells were employed in the study. After treatment with BKA (chemically synthesized; purity: >98%), several biochemical analyses were carried out. RESULTS: LTED cells were categorized into an oxidative phenotype. When LTED cells were treated with BKA, lactate dehydrogenase A (LDH-A)/pyruvate dehydrogenase kinase 4 (PDK4) were down-regulated, thereby prompting the aggressive use of glucose via mitochondrial oxidative phosphorylation and induction of cell death responses. These effects of BKA were not observed in the other breast cancer cells analyzed. CONCLUSION: We suggest the potential of BKA as an experimental tool for the analysis of cancer biology in LTED cells.


Assuntos
Ácido Bongcréquico/farmacologia , Neoplasias da Mama/metabolismo , Antígenos de Neoplasias/genética , Carnitina O-Palmitoiltransferase/genética , Linhagem Celular Tumoral , DNA Topoisomerases Tipo II/genética , Proteínas de Ligação a DNA/genética , Regulação para Baixo , Estradiol , Feminino , Glucose/metabolismo , Humanos , Isoenzimas/genética , Antígeno Ki-67/genética , L-Lactato Desidrogenase/genética , Lactato Desidrogenase 5 , Mitocôndrias/metabolismo , PPAR gama/metabolismo , Proteínas Serina-Treonina Quinases/genética , Piruvato Desidrogenase Quinase de Transferência de Acetil
15.
Phys Chem Chem Phys ; 18(36): 25136-25142, 2016 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-27711527

RESUMO

We have studied the local structure and valence electronic unoccupied states of thermoelectric CsBi4Te6 and superconducting CsBi3.5Pb0.5Te6 (Tc ∼ 3 K) by extended X-ray absorption fine structure (EXAFS) and X-ray absorption near edge structure (XANES) measurements. The Bi-L3 edge EXAFS reveals wide Bi-Te distance distribution for both compounds indicating complex atomic arrangements in the studied system. The mean square relative displacements (MSRDs) of the Bi-Te bond distances appear largely increased in Pb substituted system due to larger overall local disorder, however, one of the Bi-Te bonds shows a reduced disorder. On the other hand, the Bi-L3 edge XANES is hardly affected by Pb substitution while the Te-L1 edge XANES reveals increased density of unoccupied Te 5p states. This suggests that the carriers introduced by the Pb substitution in CsBi4-xPbxTe6 preferentially goes on Te sites. Similarly, the Cs-L3 edge XANES also shows small changes due to Pb-substitution and reduced local disorder indicated by the reduced width of the Cs-L3 edge white line. We have also shown that the X-ray photoemission spectroscopy (XPS) measurements on various electronic core levels are in a qualitative agreement with the XANES results. These findings are consistent with carrier doping and a reduced disorder in one direction to be likely factors to drive the thermoelectric CsBi4Te6 into a bulk superconductor by Pb-substitution in CsBi4-xPbxTe6.

16.
Sci Rep ; 6: 30946, 2016 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-27499373

RESUMO

Pressure dependence of the electronic and crystal structures of KxFe2-ySe2, which has pressure-induced two superconducting domes of SC I and SC II, was investigated by x-ray emission spectroscopy and diffraction. X-ray diffraction data show that compressibility along the c-axis changes around 12 GPa, where a new superconducting phase of SC II appears. This suggests a possible tetragonal to collapsed tetragonal phase transition. X-ray emission spectroscopy data also shows the change in the electronic structure around 12 GPa. These results can be explained by the scenario that the two SC domes under pressure originate from the change of Fermi surface topology. Our results here show the pronounced increase of the density of states near the Fermi surface under pressure with a structural phase transition, which can help address our fundamental understanding for the appearance of the SC II phase.

17.
J Biol Chem ; 291(13): 7017-28, 2016 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-26797126

RESUMO

Iron is an important biological catalyst and is critical for DNA synthesis during cell proliferation. Cellular iron uptake is enhanced in tumor cells to support increased DNA synthesis. Circadian variations in DNA synthesis and proliferation have been identified in tumor cells, but their relationship with intracellular iron levels is unclear. In this study, we identified a 24-h rhythm in iron regulatory protein 2 (IRP2) levels in colon-26 tumors implanted in mice. Our findings suggest that IRP2 regulates the 24-h rhythm of transferrin receptor 1 (Tfr1) mRNA expression post-transcriptionally, by binding to RNA stem-loop structures known as iron-response elements. We also found thatIrp2mRNA transcription is promoted by circadian clock genes, including brain and muscle Arnt-like 1 (BMAL1) and the circadian locomotor output cycles kaput (CLOCK) heterodimer. Moreover, growth in colon-26(Δ19) tumors expressing the clock-mutant protein (CLOCK(Δ19)) was low compared with that in wild-type colon-26 tumor. The time-dependent variation of cellular iron levels, and the proliferation rate in wild-type colon-26 tumor was decreased by CLOCK(Δ19)expression. Our findings suggest that circadian organization contributes to tumor cell proliferation by regulating iron metabolism in the tumor.


Assuntos
Relógios Circadianos/genética , Neoplasias do Colo/genética , Regulação Neoplásica da Expressão Gênica , Proteína 2 Reguladora do Ferro/genética , Ferro/metabolismo , Receptores da Transferrina/genética , Fatores de Transcrição ARNTL/genética , Fatores de Transcrição ARNTL/metabolismo , Animais , Proteínas CLOCK/deficiência , Proteínas CLOCK/genética , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Linhagem Celular Tumoral , Colo/metabolismo , Colo/patologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Deleção de Genes , Humanos , Proteína 1 Reguladora do Ferro/genética , Proteína 1 Reguladora do Ferro/metabolismo , Proteína 2 Reguladora do Ferro/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Transplante de Neoplasias , Proteínas Circadianas Period/genética , Proteínas Circadianas Period/metabolismo , Multimerização Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores da Transferrina/metabolismo , Elementos de Resposta , Transdução de Sinais
18.
J Toxicol Sci ; 40(2): 223-33, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25786526

RESUMO

Bongkrekic acid (BKA), an antibiotic isolated from Pseudomonas cocovenans, is an inhibitory molecule of adenine nucleotide translocase. Since this translocase is a core component of the mitochondrial permeability transition pore (MPTP) formed by apoptotic stimuli, BKA has been used as a tool to abrogate apoptosis. However, the other biochemical properties of BKA have not yet been resolved. Although the definition of a fatty acid is a carboxylic acid (-COOH) with a long hydrocarbon chain (tail), when focused on the chemical structure of BKA, the molecule was revealed to be a branched unsaturated tricarboxylic acid that resembled the structure of polyunsaturated fatty acids (PUFAs). Peroxisome proliferator-activated receptors (PPARs) consist of a subfamily of three isoforms: α, ß, and γ, the ligands of which include PUFAs. Using completely synthesized BKA together with simplified BKA derivatives (purity: > 98%), we herein demonstrated the utility of BKA as a selective activator of the human PPARγ isoform, which may not be associated with the anti-apoptotic nature of BKA. We also discussed the possible usefulness of BKA.


Assuntos
Antibacterianos/farmacologia , Ácido Bongcréquico/química , Ácido Bongcréquico/farmacologia , PPAR gama/metabolismo , Apoptose , Araquidonato 15-Lipoxigenase , Ácido Bongcréquico/análogos & derivados , Ácido Bongcréquico/síntese química , Humanos , Células MCF-7 , Translocases Mitocondriais de ADP e ATP/antagonistas & inibidores , Isoformas de Proteínas/metabolismo
19.
Appl Phys Lett ; 106(5): 052601, 2015 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-25713469

RESUMO

We have observed zero resistivity above 10 K and an onset of resistivity reduction at 25.2 K in a heavily B-doped diamond film. However, the effective carrier concentration is similar to that of superconducting diamond with a lower Tc. We found that the carrier has a longer mean free path and lifetime than in the previous report, indicating that this highest Tc diamond has better crystallinity compared to that of other superconducting diamond films. In addition, the susceptibility shows a small transition above 20 K in the high quality diamond, suggesting a signature of superconductivity above 20 K. These results strongly suggest that heavier carrier doped defect-free crystalline diamond could give rise to high Tc diamond.

20.
Toxicology ; 326: 18-24, 2014 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-25291031

RESUMO

We recently reported that Δ(9)-tetrahydrocannabinol (Δ(9)-THC), a major cannabinoid component in Cannabis Sativa (marijuana), significantly stimulated the expression of fatty acid 2-hydroxylase (FA2H) in human breast cancer MDA-MB-231 cells. Peroxisome proliferator-activated receptor α (PPARα) was previously implicated in this induction. However, the mechanisms mediating this induction have not been elucidated in detail. We performed a DNA microarray analysis of Δ(9)-THC-treated samples and showed the selective up-regulation of the PPARα isoform coupled with the induction of FA2H over the other isoforms (ß and γ). Δ(9)-THC itself had no binding/activation potential to/on PPARα, and palmitic acid (PA), a PPARα ligand, exhibited no stimulatory effects on FA2H in MDA-MB-231 cells; thus, we hypothesized that the levels of PPARα induced were involved in the Δ(9)-THC-mediated increase in FA2H. In support of this hypothesis, we herein demonstrated that; (i) Δ(9)-THC activated the basal transcriptional activity of PPARα in a concentration-dependent manner, (ii) the concomitant up-regulation of PPARα/FA2H was caused by Δ(9)-THC, (iii) PA could activate PPARα after the PPARα expression plasmid was introduced, and (iv) the Δ(9)-THC-induced up-regulation of FA2H was further stimulated by the co-treatment with L-663,536 (a known PPARα inducer). Taken together, these results support the concept that the induced levels of PPARα may be involved in the Δ(9)-THC up-regulation of FA2H in MDA-MB-231 cells.


Assuntos
Neoplasias da Mama/enzimologia , Dronabinol/farmacologia , Oxigenases de Função Mista/biossíntese , PPAR alfa/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Citocromo P-450 CYP1A1/biossíntese , Citocromo P-450 CYP1A1/genética , Relação Dose-Resposta a Droga , Indução Enzimática , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Indóis/farmacologia , Oxigenases de Função Mista/genética , PPAR alfa/genética , PPAR alfa/metabolismo , Fatores de Tempo , Transcrição Gênica , Transfecção , Regulação para Cima
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