ESIPT-AIE active Schiff base based on 2-(2'-hydroxyphenyl)benzo-thiazole applied as multi-functional fluorescent chemosensors.

Three AIE (aggregation-induced emission)-ESIPT (excited-state intramolecular proton transfer) active 2-(2-hydroxyphenyl)benzothiazole derivatives, HL, HL and HL with one, two and three rotatable phenyl groups, were obtained and characterized. Their AIE properties in THF/HEPES solution were investigated in detail. HL shows the best AIE performance with 71-fold fluorescence enhancement, while HL only shows a 9-fold enhancement.

The glycine hinge of transmembrane segment 2 modulates the subcellular localization and gating properties in TREK channels.

TWIK-Related K channels (TREK), including TREK-1 and TREK-2, belong to the TREK/TRAAK subclass of two-pore domain K (K2P) family. The important functions of transmembrane segment 4 (M4)-glycine hinge in TREK channel gating have been characterized, but the roles of M2-hinge (the equivalent residue of M4-hinge) remain unclear. Here, by characterizing the macroscopic currents, subcellular localization and gating properties of their M2-hinge mutants (G166A for TREK-1 and G196A for TREK-2), we investigated the functions of M2-hinge.

Coordination-Directed Stacking and Aggregation-Induced Emission Enhancement of the Zn(II) Schiff Base Complex.

2-(Trityliminomethyl)-quinolin-8-ol (HL) and its Zn(II) complex were synthesized and characterized by single-crystal X-ray diffraction. HL is an unsymmetrical molecule and coordinated with Zn(II) ion to form ZnL in the antiparallel-mode arrangement via Zn-O (hydroxyl group) and Zn-N (quinoline ring) of HL. A high degree of ZnL molecules ordering stacking is formed by the coordination bonds and intermolecular π-π interactions, in which head-to-tail arrangement (J-mode stacking) for L is found.

Four new taraxastane-type triterpenoic acids from Cirsium setosum.

Four new taraxastane-type triterpenoids acids 3β,22α-dihydroxy-20-taraxasten-30-oic acid (1), 3β-hydroxy-22-oxo-20-taraxasten-30-oic acid (2), 3-oxo-22α-hydroxy-20- taraxasten-30-oic acid (3), and 3β,19β-dihydroxy-20-taraxasten-30-oic acid (4) were isolated and characterized from Cirsium setosum (Willd.) MB. Their structures were determined by the combination of 1D and 2D NMR experiments ((1)H-(1)HCOSY, HSQC, HMBC and ROESY) and mass spectrometry.

Intersubunit Concerted Cooperative and cis-Type Mechanisms Modulate Allosteric Gating in Two-Pore-Domain Potassium Channel TREK-2.

In response to diverse stimuli, two-pore-domain potassium channel TREK-2 regulates cellular excitability, and hence plays a key role in mediating neuropathic pain, mood disorders and ischemia through. Although more and more input modalities are found to achieve their modulations via acting on the channel, the potential role of subunit interaction in these modulations remains to be explored. In the current study, the deletion (lack of proximal C-terminus, ΔpCt) or point mutation (G312A) was introduced into TREK-2 subunits to limit K(+) conductance and used to report subunit stoichiometry.

Allosteric coupling between proximal C-terminus and selectivity filter is facilitated by the movement of transmembrane segment 4 in TREK-2 channel.

TREK-2, a member of two-pore-domain potassium channel family, regulates cellular excitability in response to diverse stimuli. However, how such stimuli control channel function remains unclear. Here, by characterizing the responses of cytosolic proximal C-terminus deletant (ΔpCt) and transmembrane segment 4 (M4)-glycine hinge mutant (G312A) to 2-Aminoethoxydiphenyl borate (2-APB), an activator of TREK-2, we show that the transduction initiated from pCt domain is allosterically coupled with the conformation of selectivity filter (SF) via the movements of M4, without depending on the original status of SF.

The isoforms generated by alternative translation initiation adopt similar conformation in the selectivity filter in TREK-2.

TREK-2 (TWIK-related K(+) channel-2), a member of two-pore domain potassium (K2P) channel family, tunes cellular excitability via conducting leak or background currents. In TREK-2, the isoforms generated by alternative translation initiation (ATI) mechanism exhibit large divergence in unitary conductance, but similar in selectivity to K(+). Up to now, the structural basis for this similarity in ion selectivity is unknown.

Mas-related G protein-coupled receptor D is coupled to endogenous calcium-activated chloride channel in Xenopus oocytes.

Mas-related G protein-coupled receptor D (MrgD) is expressed almost exclusively in nociceptive primary sensory neurons and the neurons located in stratum granulosum of skin. More and more evidence suggest that MrgD plays an important role in pain sensation and/or transduction. Recent studies have demonstrated that the receptor is also involved in itch sensation in both mouse and human.

Aquaporin-4 deficiency attenuates opioid dependence through suppressing glutamate transporter-1 down-regulation and maintaining glutamate homeostasis.

Background: Glutamate homeostasis plays a critical role in mediating the addiction-related behaviors. Therefore, preventing the disruption or reestablishing of it is a novel strategy for the treatment of addiction. Glutamate transporters are responsible for clearing extracellular glutamate and maintaining glutamate homeostasis.

Antidepressant-like effects of 071031B, a novel serotonin and norepinephrine reuptake inhibitor.

SNRIs (serotonin and norepinephrine reuptake inhibitors) have been proposed to exert increased therapeutic efficacy or be faster acting compared to commonly used antidepressants. In this study, we performed in vitro binding and uptake assays and in vivo behavioral tests to assess the pharmacological properties and antidepressant-like efficacy of the compound 071031B; we also performed cytotoxicity tests using HepG2 cells and SH-SY5Y cells to predict the toxicity of 071031B. In vitro, 071031B had high affinity for both serotonin transporters and norepinephrine transporters prepared from rat cortex tissue (Ki=2.

External Ba2+ block of the two-pore domain potassium channel TREK-1 defines conformational transition in its selectivity filter.

TREK-1 is a member of the two-pore domain potassium channel family that is known as a leak channel and plays a key role in many physiological and pathological processes. The conformational transition of the selectivity filter is considered as an effective strategy for potassium channels to control the course of potassium efflux. It is well known that TREK-1 is regulated by a large volume of extracellular and intracellular signals.

Knockdown of ASIC2a subunit aggravates injury of rat C6 glioma cells in acidosis.

Acid-sensing ion channel 1a (ASIC1a) and 2a (ASIC2a) subunits are widely expressed throughout mammalian central nervous system. Activation of Ca²⁺-permeable ASIC1a homomultimers is largely responsible for acidosis-mediated, glutamate receptorindependent, ischemic neuronal injury. The function of ASIC2a in brain ischemia is less known except that transient global ischemia induces ASIC2a protein expression up-regulation in neurons that survived ischemia.

New cytotoxic azaphilones from Monascus purpureus-fermented rice (red yeast rice).

Using a cell-based cytotoxicity assay three new cytotoxic azaphilones, including two stereoisomers and designated monapurones A-C (1-3), were isolated from the extract of Monascus purpureus-fermented rice (red yeast rice). Their structures were elucidated by detailed interpretation of spectroscopic and chemical data. The relative configurations were assigned on the basis of analysis of NOE data, and the absolute configurations were determined by direct comparison of their CD spectra with those of known azaphilones and chemical correlations.

Involvement of tissue transglutaminase in endothelin 1-induced hypertrophy in cultured neonatal rat cardiomyocytes.

A potential link between tissue-type transglutaminase (tTG) and cardiac hypertrophy was suggested recently. However, whether tTG is implicated in hypertrophic agonist-induced cardiac hypertrophy is not yet known. The purpose of this study was to investigate the effects of tTG on cardiomyocyte hypertrophy induced by endothelin (ET) 1.

[Yin-yang relationship between oncogene and antioncogene].

Oncogene and antioncogene play contrary effects on the cell growth and proliferation controlling process, and cancer occurs when the presence of imbalance expression between them. That means there is yin-yang relationship between oncogene (yang) and antioncogene (yin), and also inside both of them. Taking the oncogene myc and antioncogene p53 for example, the yin gene p53 acts, in the yin side, to promote cell apoptosis and inhibit cell growth, while in the yang side, it facilitates for repairing the injured DNA to keep cell survival; the yang gene myc, promoting cell growth and proliferation in the yang side and inducing cell apoptosis in the yin side.

[Effects of melatonin on the voltage-gated delayed rectifier potassium channels of cultured hippocampal neurons of new-born rats].

Objective: To investigate the effects of melatonin on voltage-gated delayed rectifier potassium channels.

Methods: Hippocampus neurons were obtained from newborn Wistar rat and cultured. Primary cultured for 7 to 12 days of new-born Wistar rat were selected as objectives.

Pharmacological characterization of 3-azabicyclo[3,2,1] octane-1-yl-l-leucyl-d-tryptophanyl-d-4-Cl-phenylalanine: A novel ET(A) receptor-selective antagonist.

Background And Objectives: Pulmonary hypertension is a kind of disease associated with a very high rate of mortality. There are not many effective drugs for the treatment of pulmonary hypertension. Treatment with ET-1 receptor antagonists was proved to be effective in the treatment of pulmonary hypertension.

Analgesic activity of ZC88, a novel N-type voltage-dependent calcium channel blocker, and its modulation of morphine analgesia, tolerance and dependence.

ZC88 is a novel non-peptide N-type voltage-sensitive calcium channel blocker synthesized by our institute. In the present study, the oral analgesic activity of ZC88 in animal models of acute and neuropathic pain, and functional interactions between ZC88 and morphine in terms of analgesia, tolerance and dependence were investigated. In mice acetic acid writhing tests, ZC88 (10-80 mg/kg) administered by oral route showed significant antinociceptive effects in a dose-dependent manner.

Silencing of herg gene by shRNA inhibits SH-SY5Y cell growth in vitro and in vivo.

Overexpression of human ether-à-go-go (eag) related gene (herg) contributes to the progression and metastasis of a variety of tumors of different histogenesis, which implies that the herg gene could provide a promising target on tumor therapy. In the present study, plasmid-mediated expression of shRNA-herg1 and shRNA-herg1/1b was employed to silence the herg gene expression in human neuroblastoma SH-SY5Y cell lines. The inhibition of the target gene expression was confirmed by RT-PCR and Western blot.

Underlying mechanism of ASIC1a involved in acidosis-induced cytotoxicity in rat C6 glioma cells.

Aim: To investigate the underlying mechanism of acid-sensing ion channel (ASIC) 1a involved in the acidosis-induced cytotoxicity of rat C6 glioma cells.

Methods: The stable ASIC1a-silenced C6 cells built with the RNA interference technology were confirmed by RT-PCR and Western blot analysis. Intracellular calcium ([Ca2+]i) in both the wild-type rat C6 glioma cells and the ASIC1a-silenced C6 cells were analyzed before and after acid application/exposure with the calcium imaging experiment.

Inhibition of acid-induced apoptosis by targeting ASIC1a mRNA with short hairpin RNA.

Aim: To study the role of acid-sensing ion channel (ASIC) 1a in the cell death and apoptosis induced by extracellular acid in C6 glioma cells.

Methods: The stable ASIC1a-silenced C6 cell line, built with RNA interference technology, were confirmed by RT-PCR and Western blot analysis. The cell viability following acid exposure was analyzed with lactate dehydrogenase (LDH) and 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay.

[Ion channels and tumor].

This review illuminates the current approaches of ion channels and tumor. Potassium, calcium, chloride channnels and others are abnormally expressed in the membrane of tumor cells. They are crucial for tumor development and growth.

Agmatine inhibits morphine-induced locomotion sensitization and morphine-induced changes in striatal dopamine and metabolites in rats.

The effects of agmatine on morphine-induced locomotion sensitization and morphine-induced changes in extracellular striatal dopamine (DA) and DA metabolites were studied. The locomotor response to morphine challenge (3 mg/kg, s.c.

Modulation of agmatine on calcium signal in morphine-dependent CHO cells by activation of IRAS, a candidate for imidazoline I1 receptor.

The present study investigated the effects of agmatine action on imidazoline I1 receptor antisera-selected protein (IRAS), a candidate for imidazoline I1 receptor, on prolonged morphine-induced adaptations of calcium signal and long-lasting alterations in gene expression to further elucidate the role of IRAS in opioid dependence. Two cell lines, Chinese hamster ovary cells expressing mu opioid receptor alone (CHO-mu) and expressing mu opioid receptor and IRAS together (CHO-mu/IRAS), were used. After chronic treatment with morphine for 48 h, naloxone induced a significant elevation of intracellular calcium concentration ([Ca2+]i) in CHO-mu and CHO-mu/IRAS cells.

Involvement of phosphatidylcholine-selective phospholipase C in activation of mitogen-activated protein kinase pathways in imidazoline receptor antisera-selected protein.

Imidazoline receptor antisera-selected protein (IRAS) is considered as a candidate for the I1-imidazoline receptor (I1R), but the signaling pathway mediated by IRAS remains unknown. In our study, the signal transduction pathways of IRAS were investigated in CHO cells stably expressing IRAS (CHO-IRAS), and compared to the native I1R signaling pathways. Rilmenidine or moxonidine (10 nM-100 microM), I1R agonists, failed to stimulate [35S]-GTPgammaS binding in CHO-IRAS cell membrane preparations, suggesting that G protein may not be involved in IRAS signaling pathway.