Isolation and Characterization of Activators of ERK/MAPK from Citrus Plants

Extracellular signal-regulated kinases 1/2 (ERK1/2), components of the mitogen-activated protein kinase (MAPK) signaling cascade, have been recently shown to be involved in synaptic plasticity and in the development of long-term memory in the central nervous system (CNS). We therefore examined the ability of Citrus compounds to activate ERK1/2 in cultured rat cortical neurons, whose activation might have a protective effect against neurodegenerative neurological disorders. Among the samples tested, extracts prepared from the peels of Citrus grandis (Kawachi bankan) were found to have the greatest ability to activate ERK1/2. The active substances were isolated by chromatographic separation, and one of them was identified to be 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF). HMF significantly induced the phosphorylation of cAMP response element-binding protein (CREB), a downstream target of activated ERK1/2, which appears to be a critical step in the signaling cascade for the structural changes underlying the development of long-term potentiation (LTP). In addition, the administration of HMF into mice treated with NMDA receptor antagonist MK-801 restored the MK-801-induced deterioration of spatial learning performance in the Morris mater-maze task. Taken together, these results suggest that HMF is a neurotrophic agent for treating patients with memory disorders

KLHDC10 Activates ASK1 by Suppressing PP5

Reactive oxygen species (ROS)-induced activation of Apoptosis signal-regulating kinase 1 (ASK1) plays crucial roles in oxidative stress-mediated cell death through the activation of the JNK and p38 MAPK pathways. However, the regulatory mechanism of ASK1 in the oxidative stress response remains to be elucidated. Here, we identified the kelch repeat protein, Slim, as an activator of ASK1 through a Drosophila misexpression screen. We also performed a proteomics screen and revealed that Kelch domain containing 10 (KLHDC10), a mammalian ortholog of Slim, interacted with Protein phosphatase 5 (PP5), which has been shown to inactivate ASK1 in response to ROS. KLHDC10 bound to the phosphatase domain of PP5 and suppressed its phosphatase activity. Moreover, KLHDC10 was required for H2O2-induced sustained activation of ASK1 and cell death in Neuro2A cells. These findings suggest that Slim/KLHDC10 is an activator of ASK1, contributing to oxidative stress-induced cell death through the suppression of PP5

Probing ultrafast spin-relaxation and precession dynamics in a cuprate Mott insulator with 7-fs optical pulses

A charge excitation in a two-dimensional Mott insulator is strongly coupled with the surrounding spins, which is observed as magnetic-polaron formations of doped carriers and a magnon sideband in the Mott-gap transition spectrum. However, the dynamics related to the spin sector are difficult to measure. Here, we show that pump-probe reflection spectroscopy with 7-fs laser pulses can detect the optically induced spin dynamics in Nd$_2$CuO$_4$, a cuprate Mott insulator. The bleaching signal at the Mott-gap transition is enhanced at $\sim$18 fs, which corresponds to the spin-relaxation time in magnetic-polaron formations and is characterized by the exchange interaction. More importantly, ultrafast coherent oscillations appear in the time evolutions of the reflectivity changes, and their frequencies (1400-2700 cm$^{-1}$) are equal to the probe energy measured from the Mott-gap transition peak. These oscillations originate from interferences between charge excitations with two magnons and provide direct evidence for charge-spin coupling.Comment: 20 pages including 4 figures (Supplementary materials: 11 pages including 4 figures

Neurotrophic Effect of Citrus Auraptene: Neuritogenic Activity in PC12 Cells

The activation of extracellular signal-regulated kinases (ERK) leads to a number of cellular changes associated with the development of long-term memory. Using cultured cortical neurons, we previously showed that the n-hexane extract prepared from the peels of Citrus grandis (Kawachi bankan) induces the activation of ERK1/2 and that one of the compounds with this ability in the extract is 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF), a Citrus polymethoxyflavone. In fact, we found that HMF has the ability to rescue mice from drug-induced learning impairment. This hexane extract contains auraptene (AUR), a coumarin derivative with a monoterpene unit, together with HMF. The present study was designed to investigate the effect of AUR in vitro. Our results show that 1) AUR had the ability to induce the activation of ERK1/2 in not only cortical neurons but also the rat pheochromocytoma cell line (PC12 cells), which is a model system for studies on neuronal proliferation and differentiation; and 2) AUR had the ability to promote neurite outgrowth from PC12 cells

Investigating the roles of T224 and T232 in the oxidation of cinnamaldehyde catalyzed by myxobacterial CYP260B1

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/136018/1/feb212519-sup-0001-Supinfo.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/136018/2/feb212519.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/136018/3/feb212519_am.pd

日本古来の素材や伝統技法・工芸を世界に通じる先染織物のデザインに活用するための基礎研究

　本研究は日本古来の素材や伝統技法・工芸、とりわけ播磨藍、杉原和紙など、兵庫県に古くから育まれてきた素材や技法を調査し、世界に通じる先染綿織物のデザインに活用することを目的とする。兵庫県北播磨の地場産業である播州織は、安価な海外産地との価格競争の中で生産高を激減させている。これは一地場産業の衰退だけに留まらず、北播磨の地域経済や人口の流出に直結する深刻な問題である。　今日、ラグジュアリーファッションの市場では、高感度で高品質なテキスタイルに関心が高まっている。一方、播州織においては、ジャガード織を高度に進歩させたフォトジャガードやカットジャガードなどポテンシャルの高い技術を持ってはいるが、独自の製品開発には至っていない。播州織がラグジュアリー市場の需要に応えるためには、播州織でしか生み出すことができないオリジナル性の高い製品開発が不可欠である。そのためには播州織におけるジャガード織の高度な技術を用い、日本独自の美的価値観「ジャパンクオリティ」をキーワードにオリジナル性の高い、高付加価値な先染綿織物の開発が必要である。兵庫県の伝統的な染色技法や加工技術、日本古来の素材などの調査・研究・実験を行い、播州織産元商社の株式会社丸萬の協力を得て、新たな播州織の開発を試みる基礎研究を行った。This research investigates traditional Japanese materials, techniques, and crafts, especially those of Hyogo Prefecture, such as Harima indigo and Sugihara Washi paper, and the use of those for world-class designs of yarn-dyed cotton fabric. The production of Banshu weaving, which is a local industry of Kita Harima, Hyogo Prefecture, has drastically reduced due to price competition with inexpensive overseas areas of production. This reduction isn’t just a decline in one local industry, but is a serious problem directly linked to the regional economy and the population outflow of North Harima. The interest in stylishness as well as top quality textiles is rising in today’s luxury fashion market. Banshu weaving has considerably technological potential such as photo jacquard and cut jacquard, which are greatly advanced forms of jacquard weaves, but has not developed its own unique products. In order to meet the demands of the luxury market, it is indispensable to develop highly original products that can only be produced in the area. Consequently, we have focused on the development of unique and high value-added yarn-dyed cotton fabric using the advanced technology of Banshu jacquard, in the name of "Japan Quality", which symbolizes Japan\u27s unique aesthetic values. We have conducted research and experiments on traditional dyeing techniques and processing technology in Hyogo, and the ancient materials of Japanese origin, and then conducted basic research with the cooperation of Maruman Co. Ltd., a former trading company of Banshu weaving to develop new Banshu weaves

Recent developments in bisintercalator natural products

The bisintercalator natural products are a family of nonribosomal peptides possessing a range of biological properties that include antiviral, antibiotic, and anticancer activities. The name bisintercalator is derived from the ability to directly bind to duplex DNA through two planar intercalating moieties. Although 19 members of this family of compounds have been identified over the past 50 years, the biosynthetic genes responsible for the formation of four of these molecules (thiocoraline, SW-163, triostin A, and echinomycin) were identified only recently. This recent progress opens an avenue towards understanding how Nature produces these bisintercalating products and provides the potential to develop and identify novel potent analogous lead compounds for clinical applications. This review discusses the mode of action of bisintercalators and summarizes recent genetic and biochemical insights into their biosynthetic production, analog formation, and possible mechanisms by which resistance to these compounds is achieved by their producing organisms. © 2010 Wiley Periodicals, Inc. Biopolymers 93: 777–790, 2010.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77426/1/21489_ftp.pd

Hydrogen atom versus hydride transfer in cytochrome P450 oxidations: A combined mass spectrometry and computational study

Biomimetic models of short-lived enzymatic reaction intermediates can give useful insight into the properties and coordination chemistry of transition metal complexes. In this work we investigate a high-valent iron(IV)-oxo porphyrin cation radical complex, namely [FeIV(O)(TPFPP+•)]+ where TPFPP is the dianion of 5,10,15,20-tetrakis(pentafluorophenyl) porphyrin. The [FeIV(O)(TPFPP+•)]+ ion was studied by ion-molecule reactions in a Fourier transform-ion cyclotron resonance mass spectrometer through reactivities with 1,3,5-cycloheptatriene, 1,3-cyclohexadiene and toluene. The different substrates give dramatic changes in reaction mechanism and efficiencies, whereby cycloheptatriene leads to hydride transfer, while cyclohexadiene and toluene react via hydrogen atom abstraction. Detailed computational studies point to major differences in ionization energy as well as C–H bond energies of the substrates that influence the hydrogen atom abstraction versus electron transfer pathways. The various variables that determine the pathways for hydride transfer versus hydrogen atom transfer are elucidated and discussed

Proton-coupled electron transfer reactivities of electronically divergent heme superoxide intermediates: a kinetic, thermodynamic, and theoretical study.

From Europe PMC via Jisc Publications RouterHistory: epub 2021-05-27, ppub 2021-07-01Publication status: PublishedFunder: Biotechnology and Biological Sciences Research Council; Grant(s): BB/J014478/1Heme superoxides are one of the most versatile metallo-intermediates in biology, and they mediate a vast variety of oxidation and oxygenation reactions involving O2(g). Overall proton-coupled electron transfer (PCET) processes they facilitate may proceed via several different mechanistic pathways, attributes of which are not yet fully understood. Herein we present a detailed investigation into concerted PCET events of a series of geometrically similar, but electronically disparate synthetic heme superoxide mimics, where unprecedented, PCET feasibility-determining electronic effects of the heme center have been identified. These electronic factors firmly modulate both thermodynamic and kinetic parameters that are central to PCET, as supported by our experimental and theoretical observations. Consistently, the most electron-deficient superoxide adduct shows the strongest driving force for PCET, whereas the most electron-rich system remains unreactive. The pivotal role of these findings in understanding significant heme systems in biology, as well as in alternative energy applications is also discussed