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Biochimica et biophysica acta, General subjects 21건

  1. [해외논문]   Editorial Board   SCI SCIE


    Biochimica et biophysica acta, General subjects v.1861 no.3 ,pp. i - i , 2017 , 0304-4165 ,

    초록

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  2. [해외논문]   Much more than you expected: The non-DHFR-mediated effects of methotrexate   SCI SCIE

    Sramek, Martin (Corresponding author.) , Neradil, Jakub , Veselska, Renata
    Biochimica et biophysica acta, General subjects v.1861 no.3 ,pp. 499 - 503 , 2017 , 0304-4165 ,

    초록

    Abstract Background For decades, methotrexate (MTX; amethopterin) has been known as an antifolate inhibitor of dihydrofolate reductase (DHFR), and it is widely used for the treatment of various malignancies and autoimmune diseases. Although the inclusion of MTX in various therapeutic regimens is based on its ability to inhibit DHFR and consequently to suppress the synthesis of pyrimidine and purine precursors, recent studies have shown that MTX is also able to target other intracellular pathways that are independent of folate metabolism. Scope of review The main aim of this review is to summarize the most important, up-to-date findings of studies regarding the non-DHFR-mediated mechanisms of MTX action. Major conclusions The effectiveness of MTX is undoubtedly caused by its capability to affect various intracellular pathways at many levels. Although the most important therapeutic mechanism of MTX is strongly based on the inhibition of DHFR, many other effects of this compound have been described and new studies bring new insights into the pharmacology of MTX every year. General significance Identification of these new targets for MTX is especially important for a better understanding of MTX action in new protocols of combination therapy. Highlights Methotrexate is widely used as an inhibitor of dihydrofolate reductase for decades. Methotrexate affects also pathways that are independent of folate metabolism. The diverse effects of methotrexate are apparently concentration-dependent. Identification of these new targets is important for combination therapy.

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  3. [해외논문]   An attenuated calcium signaling and pre-emptive activation of UPR pathway together contribute to ER and calcium stress resilience of Lepidopteran insect cells   SCI SCIE

    Guleria, Ayushi (Corresponding author.) , Singh, Vijaypal , Chandna, Sudhir
    Biochimica et biophysica acta, General subjects v.1861 no.3 ,pp. 504 - 521 , 2017 , 0304-4165 ,

    초록

    Highlights Lack of cytosolic calcium release by radiation recently shown in Sf9 insect cells. Sf9 cells resist cytosolic/mitochondrial calcium accumulation by ER stress agents. Calcium mediated pro-apoptotic CaMKII-JNK pathway strongly attenuated in Sf9 cells. High basal level of UPR markers indicates preemptive and protective UPR signaling. Synergy of calcium regulation and UPR enhances ER stress resistance of Sf9 cells. Graphical abstract [DISPLAY OMISSION]

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  4. [해외논문]   Study of ferritin self-assembly and heteropolymer formation by the use of Fluorescence Resonance Energy Transfer (FRET) technology   SCI SCIE

    Carmona, Fernando (Molecular Biology Laboratory, Department of Molecular and Translational Medicine (DMMT), University of Brescia, Viale Europa 11, Brescia, Italy ) , Poli, Maura (Molecular Biology Laboratory, Department of Molecular and Translational Medicine (DMMT), University of Brescia, Viale Europa 11, Brescia, Italy ) , Bertuzzi, Michela (Proteomics Platform, Department of Molecular and Translational Medicine (DMMT), University of Brescia, Viale Europa 11, Brescia, Italy ) , Gianoncelli, Alessandra (Proteomics Platform, Department of Molecular and Translational Medicine (DMMT), University of Brescia, Viale Europa 11, Brescia, Italy ) , Gangemi, Fabrizio (Laboratory of Physics, Department of Molecular and Translational Medicine (DMMT), University of Brescia, Viale Europa 11, Brescia, Italy ) , Arosio, Paolo (Molecular Biology Laboratory, Department of Molecular and Translational Medicine (DMMT), University of Brescia, Viale Europa 11, Brescia, Italy)
    Biochimica et biophysica acta, General subjects v.1861 no.3 ,pp. 522 - 532 , 2017 , 0304-4165 ,

    초록

    Abstract The high stability and strong self-assembly properties made ferritins the most used proteins for nanotechnological applications. Human ferritins are made of 24 subunits of the H- and L-type that coassemble in an almost spherical nanocage 12nm across, delimiting a large cavity. The mechanism and kinetics of ferritin self-assembly and why H/L heteropolymers formation is favored over the homopolymers remain unclarified. In order to study this, we used the Fluorescence Resonance Energy Transfer (FRET) tool by binding multiple donor or acceptor Alexa Fluor fluorophores on the outer surface of human H and L ferritins and then denaturing and reassembling them in different proportions and conditions. The FRET efficiency increase from 0.7 in the assembled allowed to study the assembly kinetics. We found that their assembly was complete in about one hour, and that the initial rate of self-assembly of H/L heteropolymers was slightly faster than that of the H/H homopolymers. Then, by adding various proportions of unlabeled H or L-chains to the FRET system we found that the presence of the L-chains displaced the formation of H-H dimers more efficiently than that of the H-chains. This favored formation of H/L heterodimers, which is the initial step in ferritin self-assembly, contributes to explain the preferred formation of H/L heteropolymers over the H or L homopolymers. Moreover, we found that the H-chains arrange at distant positions on the heteropolymeric shell until they reach a number above eight, when they start to co-localize. Highlights A FRET-based approach to characterize human ferritin self-assembly is described. Self-assembly kinetics of H/L heteropolymers are faster than for H/H homopolymers. Heterodimeric (H/L) association is preferred during H/L heteropolymers formation. H-chains arrange preferentially at distant sites on H/L heteropolymeric shells. Graphical abstract [DISPLAY OMISSION]

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  5. [해외논문]   Fyn kinase regulates translation in mammalian mitochondria   SCI SCIE

    Koc, Emine C. (Department of Biochemistry and Microbiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, United States ) , Miller-Lee, Jennifer L. (Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802, United States ) , Koc, Hasan (Department of Pharmaceutical Science and Research, School of Pharmacy, Marshall University, Huntington, WV 25755, United States)
    Biochimica et biophysica acta, General subjects v.1861 no.3 ,pp. 533 - 540 , 2017 , 0304-4165 ,

    초록

    Abstract Background Mitochondrial translation machinery solely exists for the synthesis of 13 mitochondrially-encoded subunits of the oxidative phosphorylation (OXPHOS) complexes in mammals. Therefore, it plays a critical role in mitochondrial energy production. However, regulation of the mitochondrial translation machinery is still poorly understood. In comprehensive proteomics studies with normal and diseased tissues and cell lines, we and others have found the majority of mitochondrial ribosomal proteins (MRPs) to be phosphorylated. Neither the kinases for these phosphorylation events nor their specific roles in mitochondrial translation are known. Methods Mitochondrial kinases are responsible for phosphorylation of MRPs enriched from bovine mitoplasts by strong cation-exchange chromatography and identified by mass spectrometry-based proteomics analyses of kinase rich fractions. Phosphorylation of recombinant MRPs and 55S ribosomes was assessed by in vitro phosphorylation assays using the kinase-rich fractions. The effect of identified kinase on OXPHOS and mitochondrial translation was assessed by various cell biological and immunoblotting approaches. Results Here, we provide the first evidence for the association of Fyn kinase, a Src family kinase, with mitochondrial translation components and its involvement in phosphorylation of 55S ribosomal proteins in vitro . Modulation of Fyn expression in human cell lines has provided a link between mitochondrial translation and energy metabolism, which was evident by the changes in 13 mitochondrially encoded subunits of OXPHOS complexes. Conclusions and general significance Our findings suggest that Fyn kinase is part of a complex mechanism that regulates protein synthesis and OXPHOS possibly by tyrosine phosphorylation of translation components in mammalian mitochondria. Highlights Fyn kinase is associated with mitochondrial translation machinery. Mammalian mitochondrial ribosomal proteins are Tyr-phosphorylated by Fyn kinase in vitro. Fyn regulates protein synthesis and oxidative phosphorylation in mammalian mitochondria.

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  6. [해외논문]   Acetylcholinesterase inhibitory activity of stigmasterol & hexacosanol is responsible for larvicidal and repellent properties of Chromolaena odorata   SCI SCIE

    Gade, Sriramya (Biology Division, Council for Scientific and Industrial Research - Indian Institute of Chemical Technology (Ministry of Science and Technology), Uppal Road, Tarnaka, Hyderabad 500607, India ) , Rajamanikyam, Maheshwari (Biology Division, Council for Scientific and Industrial Research - Indian Institute of Chemical Technology (Ministry of Science and Technology), Uppal Road, Tarnaka, Hyderabad 500607, India ) , Vadlapudi, Varahalarao (Biology Division, Council for Scientific and Industrial Research - Indian Institute of Chemical Technology (Ministry of Science and Technology), Uppal Road, Tarnaka, Hyderabad 500607, India ) , Nukala, Krishna Madhav (Biology Division, Council for Scientific and Industrial Research - Indian Institute of Chemical Technology (Ministry of Science and Technology), Uppal Road, Tarnaka, Hyderabad 500607, India ) , Aluvala, Rajendar (Natural Products Chemistry, Council for Scientific and Industrial Research - Indian Institute of Chemical Technology (Ministry of Science and Technology), Uppal Road, Tarnaka, Hyderabad 500607, India ) , Giddigari, Chandrasekhar (Natural Products Chemistry, Co) , Karanam, Naga Jyothi , Barua, Nabin C. , Pandey, Richa , Upadhyayula, Vijaya Saradhi V. , Sripadi, Prabhakar , Amanchy, Ramars , Upadhyayula, Suryanarayana Murty
    Biochimica et biophysica acta, General subjects v.1861 no.3 ,pp. 541 - 550 , 2017 , 0304-4165 ,

    초록

    Abstract Background Chromolaena odorata , has been traditionally known for its insect repellent property. Aim of this study was to determine larvicidal tendency of C. odorata on Culex quinquefasciatus and isolate compounds responsible for this activity and to determine the mechanism of action of these compounds. Methods C. odorata plant extract was screened for mosquito larvicidal activity. The extract was fractionated using chromatography and the bioactive fraction showing larvicidal activity was identified. The chemical nature of the compounds in the bioactive fraction was determined using NMR and Mass spectrometry. Results We identified phytosterols and alkanols to be the compounds regulating larvicidal activity in the bioactive fraction of the plant extract. Stigmasterol and 1-hexacosanol were identified to be the chief orchestrators of larvicidal activity and their mode of action has been observed to be neurotoxicity. At a molecular level both stigmasterol and 1-hexacosanol were found to be inhibiting acetylcholinesterase activity in C. quinquefasciatus & A. aegypti. The acetylcholinesterase inhibitory effect was validated in vitro using recombinant acetylcholinesterase and ex vivo in larval homogenates of Culex and Aedes . Electrophysiological studies using electroantennography have shown enhanced neural response to these compounds. Conclusions Neurotoxic effect of C. odorata derived stigmasterol and 1-hexacosanol, exerted through acetylcholinesterase inhibition was responsible for the mortality of C. quinquefasciatus , A. aegypti & Chironomus riparius . EAG studies pointed out hyper-excitability of the olfactory system by these compounds. General significance These compounds are natural agents for mosquito control that can be used in vector control as larvicidal compounds, pending further investigations. Highlights Chromolaena odorata an insect repellent plant exhibited mosquito larvicidal activity. Active compounds responsible for larvicidal activity were identified as hexacosanol and stigmasterol. Larvicidal activity was shown in Culex, Aedes and a non-mosquito dipteran Chironomus. Stigmasterol & hexacosanol cause uncoordinated neurological movements in mosquito larvae and adults. Acetylcholinesterase inhibition and neurophysiology studies confirmed neurotoxic effect of stigmasterol & hexacosanol. Graphical Abstract [DISPLAY OMISSION]

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  7. [해외논문]   Transcription factor E74A affects the ecdysone titer by regulating the expression of the EO gene in the silkworm, Bomby mori   SCI SCIE

    Sun, Wei (Corresponding author.) , Wang, Cheng-Fang , Zhang, Ze
    Biochimica et biophysica acta, General subjects v.1861 no.3 ,pp. 551 - 558 , 2017 , 0304-4165 ,

    초록

    Abstract The formation of ecdysone pulse in insects is synergistically controlled by its biosynthesis and degradation. Previous studies have revealed the feedback regulation of the prothoracic gland (PG) activity to affect the hormone synthesis. However, the molecular regulatory mechanism of the ecdysone degradation is still unclear. In this study, we showed that ecdysone oxidase (EO) gene encoding a hormone metabolism enzyme was also induced by hormone itself in the domestic silkworm, Bombyx mori . Furthermore, luciferase reporter, chromatin immunoprecipitation and electrophoretic mobility shift assays showed that ecdysone inducible transcription factor E74A could bind to the cis -regulatory elements of the EO gene. Then, down-regulating the expression of the E74A by RNA interference (RNAi) decreased the expression of the EO gene and caused a higher ecdysone titer compared with the control. Thus, our results demonstrated a new feedback regulation degradation (EO) pathway controlled by ecdysone itself through transcription factor E74A, expanding the knowledge about the regulatory system that determines the formation of ecdysone pulse. Highlights Ecdysone induce the expression of EO gene in the domesticated silkworm; Ecdysone inducible transcription factor E74A could bind to the cis-regulatory elements of the EO gene; A new feedback regulation degradation (EO) pathway is controlled by ecdysone itself through transcription factor E74A

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  8. [해외논문]   Fructose suppresses uric acid excretion to the intestinal lumen as a result of the induction of oxidative stress by NADPH oxidase activation   SCI SCIE

    Kaneko, Chihiro (Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan ) , Ogura, Jiro (Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan ) , Sasaki, Shunichi (Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan ) , Okamoto, Keisuke (Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan ) , Kobayashi, Masaki (Department of Pharmacy, Hokkaido University Hospital, Kita-14-jo, Nishi-5-chome, Kita-ku, Sapporo 060-8648, Japan ) , Kuwayama, Kaori (Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Fac) , Narumi, Katsuya , Iseki, Ken
    Biochimica et biophysica acta, General subjects v.1861 no.3 ,pp. 559 - 566 , 2017 , 0304-4165 ,

    초록

    Abstract Background A high intake of fructose increases the risk for hyperuricemia. It has been reported that long-term fructose consumption suppressed renal uric acid excretion and increased serum uric acid level. However, the effect of single administration of fructose on excretion of uric acid has not been clarified. Methods We used male Wistar rats, which were orally administered fructose (5g/kg). Those rats were used in each experiment at 12h after administration. Results Single administration of fructose suppressed the function of ileal uric acid excretion and had no effect on the function of renal uric acid excretion. Breast cancer resistance protein (BCRP) predominantly contributes to intestinal excretion of uric acid as an active homodimer. Single administration of fructose decreased BCRP homodimer level in the ileum. Moreover, diphenyleneiodonium (DPI), an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox), recovered the suppression of the function of ileal uric acid excretion and the Bcrp homodimer level in the ileum of rats that received single administration of fructose. Conclusions Single administration of fructose decreases in BCRP homodimer level, resulting in the suppression the function of ileal uric acid excretion. The suppression of the function of ileal uric acid excretion by single administration of fructose is caused by the activation of Nox. The results of our study provide a new insight into the mechanism of fructose-induced hyperuricemia. Highlights The single administration of fructose suppresses the function of uric acid excretion in the ileum. The single administration of fructose decreases in BCRP homodimer level. The activation of Nox is associated with the effects of fructose on uric acid excretion. Graphical abstract [DISPLAY OMISSION]

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  9. [해외논문]   In vivo effects of metal ions on conformation and mechanical performance of silkworm silks   SCI SCIE

    Wang, Xin (State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716, PR China ) , Li, Yi (State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716, PR China ) , Liu, Qingsong (State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716, PR China ) , Chen, Quanmei (Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016, PR China ) , Xia, Qingyou (State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716, PR China ) , Zhao, Ping (State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716, PR China)
    Biochimica et biophysica acta, General subjects v.1861 no.3 ,pp. 567 - 576 , 2017 , 0304-4165 ,

    초록

    Abstract Background The mechanism of silk fiber formation is of particular interest. Although in vitro evidence has shown that metal ions affect conformational transitions of silks, the in vivo effects of metal ions on silk conformations and mechanical performance are still unclear. Methods This study explored the effects of metal ions on silk conformations and mechanical properties of silk fibers by adding K + and Cu 2+ into the silk fibroin solutions or injecting them into the silkworms. Aimed by CD analysis, FTIR analysis, and mechanical testing, the conformational and mechanical changes of the silks were estimated. By using BION Web Server, the interactions of K + and N-terminal of silk fibroin were also simulated. Results We presented that K + and Cu 2+ induced the conformational transitions of silk fibroin by forming β-sheet structures. Moreover, the mechanical parameters of silk fibers, such as strength, toughness and Young's modulus, were also improved after K + or Cu 2+ injection. Using BION Web Server, we found that potassium ions may have strong electrostatic interactions with the negatively charged residues. Conclusion We suggest that K + and Cu 2+ play crucial roles in the conformation and mechanical performances of silks and they are involved in the silk fiber formation in vivo. General significance Our results are helpful for clarifying the mechanism of silk fiber formation, and provide insights for modifying the mechanical properties of silk fibers. Highlights Metal ions are essential for silk fiber formation in silkworm. K + and Cu 2+ participate in fiber formation by forming β-sheet structures in silks. K + and Cu 2+ can be used for improving the silk fibers mechanical properties. Graphical abstract [DISPLAY OMISSION]

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  10. [해외논문]   Protection against fine particle-induced pulmonary and systemic inflammation by omega-3 polyunsaturated fatty acids   SCI SCIE

    Li, Xiang-Yong (Laboratory for Lipid Medicine and Technology (LLMT), Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA ) , Hao, Lei (Laboratory for Lipid Medicine and Technology (LLMT), Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA ) , Liu, Ying-Hua (Laboratory for Lipid Medicine and Technology (LLMT), Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA ) , Chen, Chih-Yu (Laboratory for Lipid Medicine and Technology (LLMT), Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA ) , Pai, Victor J. (Laboratory for Lipid Medicine and Technology (LLMT), Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA ) , Kang, Jing X. (Laboratory for Lipid Medicine and Technology (LLMT), Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA)
    Biochimica et biophysica acta, General subjects v.1861 no.3 ,pp. 577 - 584 , 2017 , 0304-4165 ,

    초록

    Abstract Background Exposure to fine particulate matter, such as through air pollution, has been linked to the increased incidence of chronic diseases. However, few measures have been taken to reduce the health risks associated with fine particle exposure. The identification of safe and effective methods to protect against fine particle exposure-related damage is urgently needed. Methods We used synthetic, non-toxic, fluorescent fine particles to investigate the physical distribution of inhaled fine particles and their effects on pulmonary and systemic inflammation in mice. Tissue levels of omega-3 fatty acids were elevated via dietary supplementation or the fat-1 transgenic mouse model. Markers of pulmonary and systemic inflammation were assessed. Results We discovered that fine particulate matter not only accumulates in the lungs but can also penetrate the pulmonary barrier and travel into other organs, including the brain, liver, spleen, kidney, and testis. These particles induced both pulmonary and systemic inflammation and increased oxidative stress. We also show that elevating tissue levels of omega-3 fatty acids was effective in reducing fine particle-induced inflammation, whether as a preventive method (prior to exposure) or as an intervention (after exposure). Conclusions These results advance our understanding of how fine particles contribute to disease development and suggest that increasing tissue omega-3 levels may be a promising nutritional means for reducing the risk of diseases induced by particle exposure. General significance Our findings demonstrate that elevating tissue omega-3 levels can prevent and treat fine particle-induced health problems and thereby present an immediate, practical solution for reducing the disease burden of air pollution. Highlights Inhaled fine particles are visibly shown to penetrate into multiple organs. Fine particle exposure induces pulmonary and systemic inflammation. Enriched tissue omega-3 levels prevent against particle-induced inflammation. Dietary omega-3 supplementation ameliorates particle-induced inflammation. Increasing omega-3 intake could help manage pollution-related health problems.

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