ORCID Profile
0000-0002-4716-5158
Current Organisations
Griffith University
,
University of South Australia
,
Harbin Medical University
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Publisher: Elsevier BV
Date: 10-2021
Publisher: Elsevier BV
Date: 10-2022
DOI: 10.1016/J.ECOENV.2022.114056
Abstract: Bacteria possess protective mechanisms against excess Mn(Ⅱ) to reduce its toxicity. Stenotrophomonas sp. MNB17 showed high Mn(Ⅱ) removal capacity (92.24-99.16 %) by forming Mn-precipitates (MnCO
Publisher: Springer Science and Business Media LLC
Date: 29-08-2017
DOI: 10.1038/S41598-017-06371-0
Abstract: Ca 2+ release activated Ca 2+ (CRAC) channels composed of two cellular proteins, Ca 2+ -sensing stromal interaction molecule 1 (STIM1) and pore-forming Orai1, are the main mediators of the Ca 2+ entry pathway activated in response to depletion of intracellular Ca 2+ stores. Previously it has been shown that the litude of CRAC current (I CRAC ) strongly depends on extracellular and intracellular pH. Here we investigate the intracellular pH (pH i ) dependence of I CRAC mediated by Orai1 and STIM1ectopically expressed in HEK293 cells. The results indicate that pH i affects not only the litude of the current, but also Ca 2+ dependent gating of CRAC channels. Intracellular acidification changes the kinetics of I CRAC , introducing prominent re-activation component in the currents recorded in response to voltage steps to strongly negative potentials. I CRAC with similar kinetics can be observed at normal pH i if the expression levels of Orai1 are increased, relative to the expression levels of STIM1. Mutations in the STIM1 inactivation domain significantly diminish the dependence of I CRAC kinetics on pH i , but have no effect on pH i dependence of I CRAC litude, implying that more than one mechanism is involved in CRAC channel regulation by intracellular pH.
Publisher: MDPI AG
Date: 27-07-2021
DOI: 10.3390/NU13082564
Abstract: Astragalus root (Huang Qi) and Shiitake mushrooms (Lentinus edodes) are both considered medicinal foods and are frequently used in traditional Chinese medicine due to their anticancer and immunomodulating properties. Here, the scientific literatures describing evidence for the anticancer and immunogenic properties of Shiitake and Astragalus were reviewed. Based on our experimental data, the potential to develop medicinal food with combined bioactivities was assessed using Shiitake mushrooms grown over Astragalus beds in a proprietary manufacturing process, as a novel cancer prevention approach. Notably, our data suggest that this new manufacturing process can result in transfer and increased bioavailability of Astragalus polysaccharides with therapeutic potential into edible Shiitake. Further research efforts are required to validate the therapeutic potential of this new Hengshan Astragalus Shiitake medicinal food.
Publisher: Medknow
Date: 22-09-2024
Publisher: Elsevier BV
Date: 03-2011
DOI: 10.1016/J.BBAMEM.2010.12.013
Abstract: Physiologically, hormone induced release of Ca²+ from intracellular stores occurs in response to inositol 1,4,5-trisphosphate (IP₃) binding to its receptors expressed on the membranes of intracellular organelles, mainly endoplasmic reticulum. These IP₃ receptors act as channels, releasing Ca²+ into the cytoplasmic space where it is responsible for regulating a host of distinct cellular processes. The depletion of intracellular Ca²+ stores leads to activation of store-operated Ca²+ channels on the plasma membrane which replenishes lost Ca²+ and sustain Ca²+ signalling. There are three isoforms of IP₃ receptor, each exhibiting distinctive properties, however, little is known about the role of each isoform in the activation of store-operated Ca²+ entry. Recent evidence suggest that at least in some cell types the endoplasmic reticulum is not a homogeneous Ca²+ store, and there might be a sub-compartment specifically linked to the activation of store-operated Ca²+ channels, and Ca²+ release activated Ca²+ (CRAC) channel in particular. Furthermore, this sub-compartment might express only certain types of IP₃ receptor but not the others. Here we show that H4IIE liver cells express all three types of IP₃ receptor, but only type 1 and to a lesser extent type 3, but not type 2, participate in the activation of CRAC current (I(CRAC)), while type 1 and type 2, but not type 3, participate in observed Ca²+ release in response to receptor stimulation. Presented results suggest that in H4IIE rat liver cells the sub-compartment of intracellular Ca²+ store linked to the activation of I(CRAC) predominantly expresses type 1 IP₃ receptors.
Publisher: Springer Science and Business Media LLC
Date: 10-03-2015
DOI: 10.1038/SREP08906
Abstract: Nicotinic acid (NA, a.k.a. vitamin B3 or niacin) can reduce blood cholesterol and low-density lipoproteins whereas increase high-density lipoproteins. However, when NA is used to treat dyslipidemias, it causes a strong side effect of cutaneous vasodilation, commonly called flushing. A recent study showed that NA may cause flushing by lowering activation threshold temperature of the heat-sensitive capsaicin receptor TRPV1 ion channel, leading to its activation at body temperature. The finding calls into question whether NA might also interact with the homologous heat-sensitive TRPV2–4 channels, particularly given that TRPV3 and TRPV4 are abundantly expressed in keratinocytes of the skin where much of the flushing response occurs. We found that NA indeed potentiated TRPV3 while inhibited TRPV2 and TRPV4. Consistent with these gating effects, NA lowered the heat-activation threshold of TRPV3 but elevated that of TRPV4. We further found that activity of TRPV1 was substantially prolonged by extracellular NA, which may further enhance the direct activation effect. Consistent with the broad gating effect on TRPV1–4 channels, evidence from the present study hints that NA may share the same activation pathway as 2-aminoethoxydiphenyl borate (2-APB), a common agonist for these TRPV channels. These findings shed new light on the molecular mechanism underlying NA regulation of TRPV channels.
Publisher: Frontiers Media SA
Date: 21-05-2020
Publisher: Springer Science and Business Media LLC
Date: 26-09-2016
DOI: 10.1038/SREP33827
Abstract: TRPV1 is a polymodal nociceptor for erse physical and chemical stimuli that interact with different parts of the channel protein. Recent cryo-EM studies revealed detailed channel structures, opening the door for mapping structural elements mediating activation by each stimulus. Towards this goal, here we have combined unstructured peptide-insertion screening (UPS) with electrophysiological and fluorescence recordings to explore structural and functional roles of the intracellular regions of TRPV1 in mediating various activation stimuli. We found that most of the tightly packed protein regions did not tolerate structural perturbation by UPS when tested, indicating that structural integrity of the intracellular region is critical. In agreement with previous reports, Ca 2+ -dependent desensitization is strongly dependent on both intracellular N- and C-terminal domains insertions of an unstructured peptide between these domains and the transmembrane core domain nearly eliminated Ca 2+ -dependent desensitization. In contrast, channel activations by capsaicin, low pH, alent cations, and even heat are mostly intact in mutant channels containing the same insertions. These observations suggest that the transmembrane core domain of TRPV1, but not the intracellular domains, is responsible for sensing these stimuli.
Publisher: Elsevier BV
Date: 11-2020
Publisher: Elsevier BV
Date: 06-2009
DOI: 10.1016/J.BIOCEL.2008.12.006
Abstract: The membrane-resident domain of chloride channels and transporters of the CLC family is composed of 18 alpha-helices (designated A to R) connected sequentially by extracellular and intracellular loops, whose functional characteristics are generally unclear. To study the relevance of the intracellular loops linking helices D and E, F and G, H and I and J and K, alanine-exchange mutagenesis, split channel strategy, GST (glutathione transferase)-pull-down methods and whole-cell patch-cl recordings were used. We investigated the possible roles of these loops in binding to the cytoplasmic, carboxyl tail (C-tail) of the protein, as well as their physiological roles in channel function. Although other interacting positions are conceivable, our results indicate that there is unlikely to be significant binding between the C-tail and any one of these in idual cytoplasmic loops. Particular loops might, however, be essential for some channel characteristics. For ex le, alanine-exchange mutation of the loop linking helix D to E eliminated channel currents of the loop linking helix H to I caused a significant shift of the open probability of fast gating (P(o)(f)), towards more positive voltages and of the loop linking helix J to K locked the common gating of hClC-1 open. Therefore, the gating mechanisms of hClC-1 might not only involve the helices and the C-tail, but also involve some of the loops.
Publisher: Open Exploration Publishing
Date: 23-04-2023
Abstract: Aim: Evaluation of asthma control is the first step in the management of pediatric patient symptoms. The aim of this study was to a) validate the accuracy of the Greek version of the Asthma Control Questionnaire (ACQ) in quantifying asthma status in Greek pediatric patients b) compare the 6-item with the 7-item ACQ and c) explore the discriminatory power of the ACQ in relation to medication use. Methods: Cross-sectional analysis of pulmonary data from 64 primary school children with mild asthma (51% boys). At baseline and 6 months, pulmonary function was recorded using spirometry and asthma control using the Greek version of the ACQ. Validity was assessed using Cronbach’s alpha. Results: Cronbach’s alpha showed good internal consistency for both the 7-item and 6-item ACQ (alpha = 0.67, 0.74 respectively). No differences in scores were observed in the presence/or absence of medication therapy. Conclusions: The findings of this study showed good precision and internal consistency of the 6-item ACQ in measuring recent asthma control in Greek children of the mild-asthma phenotype, independent of forced expiratory volume in 1 second (FEV1) and medication use. This suggests that the 6-item questionnaire alone is potentially a robust tool in assessing asthma symptom control in children when pulmonary function tests (PFTs) are not feasible.
Publisher: Springer Science and Business Media LLC
Date: 02-2002
Abstract: Human Y-chromosomal binary polymorphisms have been considered to preserve the paternal genetic legacy and provide evidence on human evolution and the genetic relationships among and demographic history of different populations. To reveal the genetic origin and immigration of the Fujian Han, 13 binary markers on the Y chromosome were used to screen Fujian Han by allele-specific polymerase chain reaction. The results indicated that the M9G marker was highly prevalent (96.20%), suggesting a significant genetic drift. In addition, M122C frequency was only 22.78%, and M45A and M103T were default. The distinctive haplogroup frequencies (H1, H5, and H6/7/8) imply that the haplogroup pattern is a relatively ancestral and interim type.
Publisher: Wiley
Date: 25-12-2022
DOI: 10.1113/JP282502
Abstract: Three Orai (Orai1, Orai2, and Orai3) and two stromal interaction molecule (STIM1 and STIM2) mammalian protein homologues constitute major components of the store‐operated Ca 2+ entry mechanism. When co‐expressed with STIM1, Orai1, Orai2 and Orai3 form highly selective Ca 2+ channels with properties of Ca 2+ release‐activated Ca 2+ (CRAC) channels. Despite the high level of homology between Orai proteins, CRAC channels formed by different Orai isoforms have distinctive properties, particularly with regards to Ca 2+ ‐dependent inactivation, inhibition otentiation by 2‐aminoethyl diphenylborinate and sensitivity to reactive oxygen species. This study characterises and compares the regulation of Orai1, Orai2‐ and Orai3‐mediated CRAC current ( I CRAC ) by intracellular pH (pH i ). Using whole‐cell patch cl ing of HEK293T cells heterologously expressing Orai and STIM1, we show that I CRAC formed by each Orai homologue has a unique sensitivity to changes in pH i . Orai1‐mediated I CRAC exhibits a strong dependence on pH i of both current litude and the kinetics of Ca 2+ ‐dependent inactivation. In contrast, Orai2 litude, but not kinetics, depends on pH i , whereas Orai3 shows no dependence on pH i at all. Investigation of different Orai1–Orai3 chimeras suggests that pH i dependence of Orai1 resides in both the N‐terminus and intracellular loop 2, and may also involve pH‐dependent interactions with STIM1. image It has been shown previously that Orai1/stromal interaction molecule 1 (STIM1)‐mediated Ca 2+ release‐activated Ca 2+ current ( I CRAC ) is inhibited by intracellular acidification and potentiated by intracellular alkalinisation. The present study reveals that CRAC channels formed by each of the Orai homologues Orai1, Orai2 and Orai3 has a unique sensitivity to changes in intracellular pH (pH i ). The litude of Orai2 current is affected by the changes in pH i similarly to the litude of Orai1. However, unlike Orai1, fast Ca 2+ ‐dependent inactivation of Orai2 is unaffected by acidic pH i . In contrast to both Orai1 and Orai2, Orai3 is not sensitive to pH i changes. Domain swapping between Orai1 and Orai3 identified the N‐terminus and intracellular loop 2 as the molecular structures responsible for Orai1 regulation by pH i . Reduction of I CRAC dependence on pH i seen in a STIM1‐independent Orai1 mutant suggested that some parts of STIM1 are also involved in I CRAC modulation by pH i .
Publisher: Elsevier BV
Date: 07-1986
DOI: 10.1016/0376-8716(86)90087-6
Abstract: Acute morphine tolerance was induced in mice by subcutaneous (s.c.) injection of a high dose (30 or 100 mg/kg) of morphine. The degree of tolerance was estimated 5 h later. Intracerebroventricular (i.c.v.) injection of graded doses of oxytocin (OXT) dose-dependently attenuated the development of tolerance. i.c.v. injection of a specific anti-OXT serum, on the other hand, facilitated the development of tolerance. Neither OXT nor anti-OXT serum had any effect on the pain sensitivity in morphine-naive mice nor did these treatments modify the antinociceptive action of a single morphine treatment. It is concluded that the endogenous OXT of the mouse brain is normally involved in the adaptive response of the organism, leading to the development of morphine tolerance.
Publisher: Springer Science and Business Media LLC
Date: 24-11-2015
DOI: 10.1038/NG.3153
Abstract: Temple-Baraitser syndrome (TBS) is a multisystem developmental disorder characterized by intellectual disability, epilepsy, and hypoplasia or aplasia of the nails of the thumb and great toe. Here we report damaging de novo mutations in KCNH1 (encoding a protein called ether à go-go, EAG1 or KV10.1), a voltage-gated potassium channel that is predominantly expressed in the central nervous system (CNS), in six in iduals with TBS. Characterization of the mutant channels in both Xenopus laevis oocytes and human HEK293T cells showed a decreased threshold of activation and delayed deactivation, demonstrating that TBS-associated KCNH1 mutations lead to deleterious gain of function. Consistent with this result, we find that two mothers of children with TBS, who have epilepsy but are otherwise healthy, are low-level (10% and 27%) mosaic carriers of pathogenic KCNH1 mutations. Consistent with recent reports, this finding demonstrates that the etiology of many unresolved CNS disorders, including epilepsies, might be explained by pathogenic mosaic mutations.
Publisher: Portland Press Ltd.
Date: 12-06-2008
DOI: 10.1042/BJ20071489
Abstract: Human ClC-1 (skeletal muscle Cl− channel) has a long cytoplasmic C-tail (carboxyl tail), containing two CBS (cystathionine β-synthase) domains, which is very important for channel function. We have now investigated its significance further, using deletion and alanine-scanning mutagenesis, split channels, GST (glutathione transferase)-pull-down and whole-cell patch-cl ing. In tagged split-channel experiments, we have demonstrated strong binding between an N-terminal membrane-resident fragment (terminating mid-C-tail at Ser720 and containing CBS1) and its complement (containing CBS2). This interaction is not affected by deletion of some sequences, suggested previously to be important, particularly in channel gating. Contact between CBS1 and CBS2, however, may make a major contribution to assembly of functional channels from such co-expressed complements, although the possibility that C-tail fragments could, in addition, bind to other parts of the membrane-resident component has not been eliminated. We now show such an interaction between a membrane-resident component terminating at Ser720 (but with CBS1 deleted) and a complete C-tail beginning at Leu598. Channel function is rescued in patch-cl ed HEK-293T (human embryonic kidney) cells co-expressing these same fragments. From our own results and those of others, we conclude that the CBS1–CBS2 interaction is not sufficient, in itself, for channel assembly, but rather that this might normally assist in bringing some part of the CBS2/C-tail region into appropriate proximity with the membrane-resident portion of the protein. Previously conflicting and anomalous results can now be explained by an hypothesis that, for split channels to be functional, at least one membrane-resident component must include a plasma membrane trafficking signal between Leu665 and Lys680.
Publisher: Elsevier BV
Date: 12-2014
Publisher: Elsevier BV
Date: 11-2020
Publisher: MDPI AG
Date: 24-01-2023
DOI: 10.3390/BIOM13020226
Abstract: Mitochondria are widely considered the “power hub” of the cell because of their pivotal roles in energy metabolism and oxidative phosphorylation. However, beyond the production of ATP, which is the major source of chemical energy supply in eukaryotes, mitochondria are also central to calcium homeostasis, reactive oxygen species (ROS) balance, and cell apoptosis. The mitochondria also perform crucial multifaceted roles in biosynthetic pathways, serving as an important source of building blocks for the biosynthesis of fatty acid, cholesterol, amino acid, glucose, and heme. Since mitochondria play multiple vital roles in the cell, it is not surprising that disruption of mitochondrial function has been linked to a myriad of diseases, including neurodegenerative diseases, cancer, and metabolic disorders. In this review, we discuss the key physiological and pathological functions of mitochondria and present bioactive compounds with protective effects on the mitochondria and their mechanisms of action. We highlight promising compounds and existing difficulties limiting the therapeutic use of these compounds and potential solutions. We also provide insights and perspectives into future research windows on mitochondrial modulators.
Publisher: CRC Press
Date: 25-02-2015
DOI: 10.1201/B18027-51
Publisher: MDPI AG
Date: 22-12-2022
Abstract: Fuzhuan brick tea (FBT), a type of black tea, is a traditional beverage in China, especially popular among frontier ethnic groups. FBT is well-known for its health benefits, such as hypoglycemic, anti-hypertensive, anti-inflammatory, diuretic, and detoxification effects. Nevertheless, the underlying mechanisms on the molecular level are still elusive and the key compounds responsible for the health benefits are unidentified. Previous studies have mainly focused on functional studies of the water extract. However, FBT is typically cooked with butter or milk. Therefore, we hypothesized that some lipophilic components in FBT, which can be absorbed through the co-consumption of butter or milk, may play an important role in the health benefits. The present study aimed to investigate whether the liposoluble extract of FBT alleviates symptoms related to metabolic diseases and to identify the active compounds involved. By comparing the high-performance liquid chromatography (HPLC) profiles of water, milk and hexane extract, some low polarity peaks were observed in the milk and hexane extracts. Furthermore, the hexane extract treatment alleviated body weight gain, serum total cholesterol and triglyceride levels, and inhibited the accumulation of hepatic fat granules in a high-fat diet (HFD)-induced C57BL/6N mouse model. In order to identify the key functional lipophilic compounds in FBT, the hexane extract of FBT was subjected to chemical characterization. Four phenol analogs were characterized, namely, isodihydroauroglaucin (1), dihydroauroglaucin (2), tetrahydroauroglaucin (3), and flavoglaucin (4). Compounds 1 and 4 reduced the levels of total cholesterol and triglyceride in vivo. Both compounds also inhibited the high-fat diet-induced body weight gain and accumulation of fat granules in the liver of C57BL/6N mice. Isodihydroauroglaucin and flavoglaucin have therefore been identified as bioactive ingredients that contribute to the health benefits of FBT.
Publisher: Schweizerbart
Date: 13-03-2007
Publisher: Springer Science and Business Media LLC
Date: 09-03-2006
DOI: 10.1111/J.1601-5223.2005.01910.X
Abstract: It has been shown that the variants of alcohol dehydrogenase (ADH) genes exhibit great ersities among various populations and are associated with susceptibility to alcoholism. To investigate the distribution of SNPs at ADH genes in Chinese populations and the genetic relationship of these groups, we collected 467 in iduals from 15 groups distributing widely from north to south in China and genotyped 7 SNPs at ADH genes respectively. The statistic analyses of allele frequencies, estimated haplotype frequencies, pairwise linkage disequilibrium, AMOVA (analysis of molecular variance), pairwise Fst', and cluster analysis indicated (1) that six of these seven SNPs showed great variations in the 15 Chinese populations, and three of them (RsaI, SspI, EcoRI), were confirmed to be informative SNPs. However, the causative SNP ADH1B Arg47His confirmed in case-control studies could not act as significant indicator to distinguish bibulous groups from non-bibulous groups in healthy in iduals (2) haplotypes constructed with ADH SNPs could be used as markers to discern different populations in China, and six-allele haplotype "221211" was the most common one defined in present study (3) on the basis of SNPs analysis of ADH genes, the 15 populations were grouped into northern groups and southern groups. Moreover, the origin relationship among the populations was indicated according to the results of cluster analysis.
Publisher: Schweizerbart
Date: 13-09-2002
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-1990
DOI: 10.1097/00001756-199011000-00006
Abstract: The effects of pimozide, a dopamine-receptor blocker and oxytocin, a neurohypophyseal neuropeptide were investigated in mice on the cocaine-induced exploratory hyperactivity. The action of oxytocin on changes of dopaminergic neurotransmission induced by cocaine was also measured. Cocaine-induced exploratory hyperactivity could be blocked by pimozide (1 mg kg-1, s.c.). Oxytocin (0.05-1.0 micrograms) inhibited the cocaine-induced hyperactivity in an U-shaped dose-response manner. In the nucleus accumbens, oxytocin antagonized the increased dopamine disappearance, elicited by cocaine, but not in the nucleus caudatus. The data suggest that oxytocin may influence the behavioural effect of cocaine by modulating dopaminergic neurotransmission in mesolimbic dopaminergic terminal region of the brain.
Publisher: CRC Press
Date: 06-06-2023
Publisher: Informa UK Limited
Date: 25-10-2018
Publisher: Elsevier BV
Date: 11-2021
Publisher: Proceedings of the National Academy of Sciences
Date: 03-02-2014
Abstract: Acetaminophen overdose is the most common cause of acute liver failure and the leading cause of chronic liver damage requiring liver transplantation in developed countries. There are limited options for early treatment. Acetaminophen liver toxicity leads to the formation of reactive oxygen and nitrogen species which cause an increase in intracellular Ca 2+ and hepatocellular death. We show that acetaminophen-induced liver toxicity depends on Transient Receptor Potential Melanostatine 2 (TRPM2) cation channels in hepatocytes, which are activated in response to oxidative stress and are responsible for Ca 2+ overload. Lack of TRPM2 channels in hepatocytes or their pharmacological inhibition protects liver from acetaminophen toxicity. This provides evidence that TRPM2 may present a potential therapeutic target for treatment of oxidative-stress related liver diseases.
Publisher: Rockefeller University Press
Date: 16-12-2013
Abstract: Transient receptor potential vanilloid type 1 (TRPV1) channel responds to a wide spectrum of physical and chemical stimuli. In doing so, it serves as a polymodal cellular sensor for temperature change and pain. Many chemicals are known to strongly potentiate TRPV1 activation, though how this is achieved remains unclear. In this study we investigated the molecular mechanism underlying the gating effects of alent cations Mg2+ and Ba2+. Using a combination of fluorescence imaging and patch-cl analysis, we found that these cations potentiate TRPV1 gating by most likely promoting the heat activation process. Mg2+ substantially lowers the activation threshold temperature as a result, a significant fraction of channels are heat-activated at room temperature. Although Mg2+ also potentiates capsaicin- and voltage-dependent activation, these processes were found either to be not required (in the case of capsaicin) or insufficient (in the case of voltage) to mediate the activating effect. In support of a selective effect on heat activation, Mg2+ and Ba2+ cause a Ca2+-independent desensitization that specifically prevents heat-induced channel activation but does not prevent capsaicin-induced activation. These results can be satisfactorily explained within an allosteric gating framework in which alent cations strongly promote the heat-dependent conformational change or its coupling to channel activation, which is further coupled to the voltage- and capsaicin-dependent processes.
Publisher: Rockefeller University Press
Date: 16-12-2013
Abstract: Divalent cations Mg2+ and Ba2+ selectively and directly potentiate transient receptor potential vanilloid type 1 heat activation by lowering the activation threshold into the room temperature range. We found that Mg2+ potentiates channel activation only from the extracellular side on the intracellular side, Mg2+ inhibits channel current. By iding the extracellularly accessible region of the channel protein into small segments and perturbing the structure of each segment with sequence replacement mutations, we observed that the S1–S2 linker, the S3–S4 linker, and the pore turret are all required for Mg2+ potentiation. Sequence replacements at these regions substantially reduced or eliminated Mg2+-induced activation at room temperature while sparing capsaicin activation. Heat activation was affected by many, but not all, of these structural alternations. These observations indicate that extracellular linkers and the turret may interact with each other. Site-directed fluorescence resonance energy transfer measurements further revealed that, like heat, Mg2+ also induces structural changes in the pore turret. Interestingly, turret movement induced by Mg2+ precedes channel activation, suggesting that Mg2+-induced conformational change in the extracellular region most likely serves as the cause of channel activation instead of a coincidental or accommodating structural adjustment.
Publisher: Elsevier
Date: 2014
Publisher: American Chemical Society (ACS)
Date: 26-08-2022
DOI: 10.1021/ACSCHEMNEURO.1C00820
Abstract: Traditional Chinese medicine (TCM) has been around for thousands of years and is increasingly gaining popularity in the Western world to treat various complex disorders including the incurable neurodegenerative condition, Parkinson's Disease (PD). One of the many directions in recent studies of PD is utilizing the phenotypic assay, or cytological profiling, to evaluate the phenotypic changes of PD-implicated cellular components in patient-derived olfactory neuroepithelial (hONS) cells, upon treating the cells with extracts or pure compounds. To obtain small molecules for studies utilizing PD phenotyping assays,
Publisher: Elsevier BV
Date: 06-1988
DOI: 10.1016/0014-2999(88)90018-0
Abstract: The ability of the selective cyclic mu-opioid receptor antagonist, D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), to inhibit the acute and chronic effects of morphine in vivo was studied in mice. Intracerebroventricular (i.c.v.) administration of CTOP antagonized the analgesic effect of morphine in a dose-dependent manner, as measured by the heat-irradiant (tail-flick) method. CTOP was more effective than naloxone in inhibiting analgesia on a molar basis. CTOP also antagonized the acute morphine-induced hypermotility. CTOP caused withdrawal hypothermia and a loss of body weight in morphine-dependent animals. After the development of morphine-induced chronic dependence, CTOP administered i.c.v. caused a dose-dependent loss of body weight and hypothermia, and was about 10-400 times more potent than naloxone. CTOP administered alone to drugnaive mice did not cause antinociception, changes in body weight or body temperature.
Publisher: Wiley
Date: 12-06-2009
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1016/J.BCP.2018.08.038
Abstract: Recently, we and other groups revealed that gain-of-function mutations in the human ether à go-go voltage-gated potassium channel hEAG1 (K
Publisher: Frontiers Media SA
Date: 22-12-2022
Publisher: Elsevier BV
Date: 05-1985
DOI: 10.1016/0028-3908(85)90026-7
Abstract: The effects of oxytocin (OXT) and of dipeptides derived from the C-terminal portion of oxytocin (Z-prolyl-leucine and Z-prolyl-D-leucine) on the development of acute and chronic tolerance to, and dependence on morphine were tested in the mouse. Oxytocin and the dipeptides attenuated the development of acute and chronic tolerance to the antinociceptive effect of morphine and delayed the onset of the naloxone-precipitated withdrawal syndrome. Both oxytocin and Z-prolyl-D-leucine affected drug-induced behavioural responses related to dopamine (DA) in the brain. Thus, oxytocin potentiated the hypermotility induced by a large dose of apomorphine and decreased the supersensitivity of the DA receptors. Small doses of Z-prolyl-D-leucine inhibited the hypomotility elicited by a small dose of apomorphine and potentiated the hyperactivity induced by hetamine. The data indicate that both oxytocin and Z-prolyl-D-leucine affect tolerance to and dependence on morphine. While oxytocin interacts mainly with postsynaptic DA-ergic neuronal elements, the dipeptide primarily affects DA-ergic neurotransmission at the presynaptic level.
Publisher: Elsevier BV
Date: 10-2011
Publisher: Portland Press Ltd.
Date: 13-05-2011
DOI: 10.1042/BJ20102153
Abstract: Functionally, the dimeric human skeletal muscle chloride channel hClC-1 is characterized by two distinctive gating processes, fast (protopore) gating and slow (common) gating. Of these, common gating is poorly understood, but extensive conformational rearrangement is suspected. To examine this possibility, we used FRET (fluorescence resonance energy transfer) and assessed the effects of manipulating the common-gating process. Closure of the common gate was accompanied by a separation of the C-termini, whereas, with opening, the C-termini approached each other more closely. These movements were considerably smaller than those seen in ClC-0. To estimate the C-terminus depth within the cytoplasm we constructed a pair of split hClC-1 fragments tagged extracellularly and intracellularly respectively. These not only combined appropriately to rescue channel function, but we detected positive FRET between them. This restricts the C-termini of hClC-1 to a position close to its membrane-resident domain. From mutants in which fast or common gating were affected, FRET revealed a close linkage between the two gating processes with the carboxyl group of Glu232 apparently acting as the final effector for both.
Publisher: American Society for Pharmacology & Experimental Therapeutics (ASPET)
Date: 14-03-2023
Publisher: Springer Science and Business Media LLC
Date: 17-04-2008
DOI: 10.1007/S11033-008-9256-X
Abstract: Oral squamous cell carcinoma (OSCC) is a world-wide health problem and its incidence accounts for 1.9-3.5% of all malignant tumors. Transforming growth factor beta/Smads (TGF-beta/Smads) signaling pathway plays an important role in oncogenesis, but its function and molecular mechanisms in OSCC remain unclear. Expression of transforming growth factor-beta receptor type II (TbetaRII) and Smad4 was studied by immunohistochemistry in 108 OSCC patients and 10 normal controls. Function and molecular mechanisms of TGF-beta/Smads signaling pathway was then investigated in two human tongue squamous carcinoma cell lines with high and low metastasis (Tb and Tca8113) by RT-PCR, Western Blot, immunofluorescence, cell growth curve and flow cytometry (FCM), respectively. TbetaRII and Smad4 were significantly down-regulated in tumor tissues (with or without lymph node metastasis) compared to normal oral epithelium tissues (P < 0.05). TGF-beta1 induced arrest of the cell cycle rather than cell death in Tca8113 and Tb cells, and this influence was mediated by the increasing the expression and changing the location of its downstream components of TGF-beta1/Smads signaling pathway. TGF-beta1 rapidly increased the expression of p15 and p21 in both Tca8113 and Tb cells. TGF-beta1 did not increase p27 expression in Tca8113 cells, but p27 expression was increased in Tb cells. These indicated that TGF-beta1 induced G(1) arrest of cell cycle through a different regulating pathway in Tb cells compared with Tca8113 cells. Thus, we conclude that TGF-beta/Smads signaling pathway play a important role on cell growth and metastasis potential in OSCC.
Publisher: Elsevier BV
Date: 05-2021
Publisher: MDPI AG
Date: 21-02-2022
DOI: 10.3390/IJMS23042378
Abstract: A major hallmark of Parkinson’s disease (PD) is the fatal destruction of dopaminergic neurons within the substantia nigra pars compacta. This event is preceded by the formation of Lewy bodies, which are cytoplasmic inclusions composed of α-synuclein protein aggregates. A triad contribution of α-synuclein aggregation, iron accumulation, and mitochondrial dysfunction plague nigral neurons, yet the events underlying iron accumulation are poorly understood. Elevated intracellular iron concentrations up-regulate ferritin expression, an iron storage protein that provides cytoprotection against redox stress. The lysosomal degradation pathway, autophagy, can release iron from ferritin stores to facilitate its trafficking in a process termed ferritinophagy. Aggregated α-synuclein inhibits SNARE protein complexes and destabilizes microtubules to halt vesicular trafficking systems, including that of autophagy effectively. The scope of this review is to describe the physiological and pathological relationship between iron regulation and α-synuclein, providing a detailed understanding of iron metabolism within nigral neurons. The underlying mechanisms of autophagy and ferritinophagy are explored in the context of PD, identifying potential therapeutic targets for future investigation.
Start Date: 2019
End Date: 2019
Funder: Griffith University
View Funded ActivityStart Date: 2022
End Date: 2024
Funder: Michael J. Fox Foundation for Parkinson's Research
View Funded ActivityStart Date: 2017
End Date: 2018
Funder: Flinders University
View Funded ActivityStart Date: 2019
End Date: 2019
Funder: Flinders University & Yulongxiang Agricultural Development Co Ltd
View Funded ActivityStart Date: 2014
End Date: 2016
Funder: University of Queensland
View Funded ActivityStart Date: 2004
End Date: 2006
Funder: Natural Science Foundation of Heilongjiang Province
View Funded ActivityStart Date: 2003
End Date: 2005
Funder: Natural Science Foundation of Harbin
View Funded Activity