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Action Mechanisms (action + mechanism)
Selected AbstractsProtective Effect of Total Flavones of Abelmoschus manihot L. Medic Against Poststroke Depression Injury in Mice and Its Action MechanismTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 3 2009Mei Liu Abstract Total flavones of Abelmoschus manihot L. Medic (TFA) is the major active component isolated from the traditional Chinese herb Abelmoschus manihot L. Medic. We investigated the protective effect of TFA against poststroke depression (PSD) injury in mice and its action mechanism. A mouse model of PSD was induced by middle cerebral artery occlusion (MACO) 30 min/reperfusion, followed by isolation feeding and chronic unpredictable mild stress for 2 weeks. Treatment groups received TFA at three different doses (160, 80, and 40 mg/kg, p.o.) or fluoxetine (Flu, 2.5 mg/kg, p.o.) daily for 24 days. Change in behavior, brain tissue malondialdehyde (MDA) levels, and the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured. The expression of brain-derived neurotrophic factor (BDNF) was detected by immunohistochemistry, and mRNA expression of BDNF and cAMP response element-binding protein (CREB) analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Treatment with TFA (160, 80, and 40 mg/kg) significantly ameliorated mice escape-directed behavioral impairment induced by PSD, markedly reduced MDA levels, and increased the activity of SOD, GSH-Px close to normal levels. TFA administration also attenuated PSD-induced neuronal death/losses, upregulated expression of BDNF both at mRNA and protein levels, as well as CREB mRNA levels. TFA had a protective effect against PSD injury in mice. Cardioprotection involves the inhibition of lipid peroxidation and upregulation of BDNF-CREB levels in the hippocampus, which may also be important mechanism of its antidepressants. This potential protection makes TFA a promising therapeutic agent for the PSD. Anat Rec, 292:412,422, 2009. © 2009 Wiley-Liss, Inc. [source] Action Mechanism of Insulin-Mimetic Vanadyl,Allixin ComplexCHEMISTRY & BIODIVERSITY, Issue 8 2008Makoto Hiromura Abstract In the 21st century, there has been a dramatic worldwide increase in the prevalence of metabolic syndromes, including diabetes mellitus (DM). Several synthetic pharmaceutical agents have been developed and used for the treatment of type-2 DM; however, these compounds have several problems such as side effects, hypoglycemia, and weight gain. Therefore, new drugs are required for DM therapy. We have proposed that some vanadyl complexes function as potent insulin-mimetic and antidiabetic agents in type-1 and type-2 DM animal models. In this article, we review the possible action mechanism of insulin-mimetic and antidiabetic vanadyl complexes, focusing on a recently proposed complex, bis(allixinato)oxovanadium(IV), with respect to the insulin-signaling pathway in cultured adipocytes. [source] Action Mechanisms of the Secondary Metabolite Euplotin C: Signaling and Functional Role in EuplotesTHE JOURNAL OF EUKARYOTIC MICROBIOLOGY, Issue 5 2008FRANCESCA TRIELLI ABSTRACT. Among secondary metabolites, the acetylated hemiacetal sesquiterpene euplotin C has been isolated from the marine, ciliated protist Euplotes crassus, and provides an effective mechanism for reducing populations of potential competitors through its cytotoxic properties. However, intracellular signaling mechanisms and their functional correlates mediating the ecological role of euplotin C are largely unknown. We report here that, in E. vannus (an Euplotes morphospecies that does not produce euplotin C and shares with E. crasssus the same interstitial habitat), euplotin C rapidly increases the intracellular concentration of both Ca2+ and Na+, suggesting a generalized effect of this metabolite on cation transport systems. In addition, euplotin C does not induce oxidative stress, but modulates the electrical properties of E. vannus through an increase of the amplitude of graded action potentials. These events parallel the disassembling of the ciliary structures, the inhibition of cell motility, the occurrence of aberrant cytoplasmic vacuoles, and the rapid inhibition of phagocytic activity. Euplotin C also increases lysosomal pH and decreases lysosomal membrane stability of E. vannus. These results suggest that euplotin C exerts a marked disruption of those homeostatic mechanisms whose efficiency represents the essential prerequisite to face the challenges of the interstitial environment. [source] Mitochondrial copper metabolism and delivery to cytochrome c oxidaseIUBMB LIFE, Issue 7 2008Darryl Horn Abstract Metals are essential elements of all living organisms. Among them, copper is required for a multiplicity of functions including mitochondrial oxidative phosphorylation and protection against oxidative stress. Here we will focus on describing the pathways involved in the delivery of copper to cytochrome c oxidase (COX), a mitochondrial metalloenzyme acting as the terminal enzyme of the mitochondrial respiratory chain. The catalytic core of COX is formed by three mitochondrially-encoded subunits and contains three copper atoms. Two copper atoms bound to subunit 2 constitute the CuA site, the primary acceptor of electrons from ferrocytochrome c. The third copper, CuB, is associated with the high-spin heme a3 group of subunit 1. Recent studies, mostly performed in the yeast Saccharomyces cerevisiae, have provided new clues about 1) the source of the copper used for COX metallation; 2) the roles of Sco1p and Cox11p, the proteins involved in the direct delivery of copper to the CuA and CuB sites, respectively; 3) the action mechanism of Cox17p, a copper chaperone that provides copper to Sco1p and Cox11p; 4) the existence of at least four Cox17p homologues carrying a similar twin CX9C domain suggestive of metal binding, Cox19p, Cox23p, Pet191p and Cmc1p, that could be part of the same pathway; and 5) the presence of a disulfide relay system in the intermembrane space of mitochondria that mediates import of proteins with conserved cysteines motifs such as the CX9C characteristic of Cox17p and its homologues. The different pathways are reviewed and discussed in the context of both mitochondrial COX assembly and copper homeostasis. © 2008 IUBMB IUBMB Life, 60(7): 421,429, 2008 [source] Study on the Kinetics for Enzymatic Degradation of a Natural Polysaccharide, Konjac GlucomannanMACROMOLECULAR SYMPOSIA, Issue 1 2004Guangji Li Abstract The enzymatic degradation of konjac glucomannan (KGM) was conducted using ,-mannanase from an alkalophilic Bacillus sp. in the aqueous medium (pH 9.0) at 30°C. The intrinsic viscosity ([,]), molecular weight (Mw) and molecular weight distribution (MWD) of the degraded KGM were measured. The mathematical relation between [,] and Mw, [,] = 5.06 × 10,4Mw0.754, was established. The kinetic analysis reveals a dependence of the rate constant (k) on the period of reaction and the initial substrate concentration (c0) over the range of substrate concentration (1.0,2.0%) used in this work. The results indicate that the enzymatic degradation of KGM is a complex reaction combining two reaction processes with different orders. In the initial phase of degradation k is inversely proportional to c0, which is characteristic of a zeroth-order reaction; while in the following phase k is independent of c0, implying the degradation follows a first-order reaction. The reactivity difference in breakable linkages of KGM, the action mechanism of an enzyme on KGM macromolecules, and the theory concerning the formation of an enzyme-substrate complex and ,substrate saturation' can be used to explain such a kinetic behavior. In addition, the enzymatic degradation of KGM was also carried out using the other enzymes like ,-mannanase from a Norcardioform actinomycetes, ,-glucanase Finizym and a compound enzyme Hemicell as a biocatalyst. By comparing and analyzing the degradation processes of KGM catalyzed by four different enzymes, it can be observed that there is a two-stage reaction with two distinct kinetic regimes over a certain range of degradation time for each of the degradation processes. These results are useful to realize controllable degradation of polysaccharides via an environmental benign process. [source] Protective Effect of Total Flavones of Abelmoschus manihot L. Medic Against Poststroke Depression Injury in Mice and Its Action MechanismTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 3 2009Mei Liu Abstract Total flavones of Abelmoschus manihot L. Medic (TFA) is the major active component isolated from the traditional Chinese herb Abelmoschus manihot L. Medic. We investigated the protective effect of TFA against poststroke depression (PSD) injury in mice and its action mechanism. A mouse model of PSD was induced by middle cerebral artery occlusion (MACO) 30 min/reperfusion, followed by isolation feeding and chronic unpredictable mild stress for 2 weeks. Treatment groups received TFA at three different doses (160, 80, and 40 mg/kg, p.o.) or fluoxetine (Flu, 2.5 mg/kg, p.o.) daily for 24 days. Change in behavior, brain tissue malondialdehyde (MDA) levels, and the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured. The expression of brain-derived neurotrophic factor (BDNF) was detected by immunohistochemistry, and mRNA expression of BDNF and cAMP response element-binding protein (CREB) analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Treatment with TFA (160, 80, and 40 mg/kg) significantly ameliorated mice escape-directed behavioral impairment induced by PSD, markedly reduced MDA levels, and increased the activity of SOD, GSH-Px close to normal levels. TFA administration also attenuated PSD-induced neuronal death/losses, upregulated expression of BDNF both at mRNA and protein levels, as well as CREB mRNA levels. TFA had a protective effect against PSD injury in mice. Cardioprotection involves the inhibition of lipid peroxidation and upregulation of BDNF-CREB levels in the hippocampus, which may also be important mechanism of its antidepressants. This potential protection makes TFA a promising therapeutic agent for the PSD. Anat Rec, 292:412,422, 2009. © 2009 Wiley-Liss, Inc. [source] Action Mechanism of Insulin-Mimetic Vanadyl,Allixin ComplexCHEMISTRY & BIODIVERSITY, Issue 8 2008Makoto Hiromura Abstract In the 21st century, there has been a dramatic worldwide increase in the prevalence of metabolic syndromes, including diabetes mellitus (DM). Several synthetic pharmaceutical agents have been developed and used for the treatment of type-2 DM; however, these compounds have several problems such as side effects, hypoglycemia, and weight gain. Therefore, new drugs are required for DM therapy. We have proposed that some vanadyl complexes function as potent insulin-mimetic and antidiabetic agents in type-1 and type-2 DM animal models. In this article, we review the possible action mechanism of insulin-mimetic and antidiabetic vanadyl complexes, focusing on a recently proposed complex, bis(allixinato)oxovanadium(IV), with respect to the insulin-signaling pathway in cultured adipocytes. [source] In vitro evaluation of the chemoprotective action mechanisms of leontopodic acid against aflatoxin B1 and deoxynivalenol-induced cell damageJOURNAL OF APPLIED TOXICOLOGY, Issue 1 2009Stefano Costa Abstract Several in vitro studies showed that free radical scavengers possess chemopreventive properties against mycotoxin-induced cell damage which are at least partially associated with the induction of phase II detoxifying enzymes and antioxidant enzymes like glutathione S -transferase (GST) and glutathione peroxidase (GPx). The aim of this project was to study the chemopreventive effects of leontopodic acid (LA), a potent natural occurring free radical scavenger isolated from the aerial parts of Leontopodium alpinum. Different mycotoxins were evaluated in two different cell lines on the basis of their specific toxicity: aflatoxin B1 (AFB1) on HepG2 cells and deoxynivalenol (DON) on U937 cells. Cell viability and reactive oxygen species concentration were determined, and the effects of pre-treatment with LA on these parameters were investigated together with the GST and GPx activity as well as the concentration of reduced glutathione. The results show that LA protects U937 cells from DON-induced cell damage but not HepG2 cells from AFB1. Moreover LA is able to enhance GPx activity in U937, but not GST activity in HepG2. We hypothesize that the increase in detoxifying enzymes is probably the main mechanism of antioxidant mediated chemoprevention. Copyright © 2008 John Wiley & Sons, Ltd. [source] Survivin as a target for new anticancer interventionsJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 2 2005Nadia Zaffaroni Abstract Survivin is a member of the inhibitor of apoptosis protein (IAP) family, that has been implicated in both control of cell division and inhibition of apoptosis. Specifically, its anti-apoptosis function seems to be related to the ability to directly or indirectly inhibit caspases. Survivin is selectively expressed in the most common human neoplasms and appears to be involved in tumour cell resistance to some anticancer agents and ionizing radiation. On the basis of these findings survivin has been proposed and and attractive target for new anticancer interventions. Several preclinical studies have demonstrated that down-regulation of survivin expression/function, accomplished through the use of antisense oligonucleotides, dominant negative mutants, ribozymes, small interfering RNAs and cyclin-dependent kinase inhibitors, increased the apoptotic rate, reduced tumor-growth potential and sensitized tumor cells to chemotherapeutic drugs with different action mechanisms and ,-irradiation in in vitro and in vivo models of different human tumor types. [source] 2-(4-methylphenyl)-1,3-selenazol-4-one induces apoptosis by different mechanisms in SKOV3 and HL 60 cellsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2006Hak Jun Ahn Abstract We examined the ability of the synthetic selenium compound, 2-(4-methylphenyl)-1,3-selenazol-4-one (hereafter designated 3a), to induce apoptosis in a human ovarian cancer cell line (SKOV3) and a human leukemia cell line (HL-60). Flow cytometry showed that 3a treatment induced apoptosis in both cell lines to degrees comparable to that of the positive control, paclitaxel. Apoptosis was measured by PS externalization, DNA fragmentation and decreased mitochondrial membrane potential (MMP). However, analysis of the mechanism of action revealed differences between the responses of the two cell lines. Treatment with 3a arrested the cell cycle and induced caspase-3 activation in HL-60 cells, but not in SKOV3 cells. In contrast, 3a treatment induced apoptosis through translocation of AIF, a novel pro-apoptotic protein, in SKOV3 cells, but not in HL-60 cells. Collectively, our data demonstrated that 3a induced apoptosis in both cell lines, but via different action mechanisms. J. Cell. Biochem. 99: 807,815, 2006. © 2006 Wiley-Liss, Inc. [source] Flooding and grazing promote germination and seedling establishment in the perennial grass Paspalum dilatatumAUSTRAL ECOLOGY, Issue 3 2009PATRICIA S. CORNAGLIA Abstract Seed germination and seedling emergence are key processes for population recruitment. Flooding and grazing are disturbances forming gaps that may strongly influence recruitment patterns in space and time, but their combined effects and action mechanisms have rarely been addressed. In this study we analysed the effects of microhabitat conditions associated with winter flooding and spring-summer defoliation on seed germination and seedling establishment of Paspalum dilatatum, a dominant perennial C4 grass in native grasslands of the Flooding Pampa, Argentina. The dynamics of seedling emergence from natural seed banks and buried seeds was studied in a factorial experiment with flooding and defoliation treatments applied to soil monoliths (mesocosms) collected from natural grassland. Additional laboratory experiments were applied to investigate seed germination under different combinations of temperature, light quality and simulated flooding. Seed germination and seedling emergence of P. dilatatum were promoted by flooding and high intensity defoliation. Gaps generated by flooding were maintained by high intensity defoliation exercising a synergistic effect on survival seedlings. Flooding resulted in the breaking of seed dormancy and higher germination rates associated with alternating temperature and the activation of the phytochrome system. Our results indicate that microhabitat conditions associated with the disturbances forming gaps, such as flooding and heavy grazing, synergistically promote the recruitment process of this dominant grass species. [source] Sodium butyrate induces P53-independent, Fas-mediated apoptosis in MCF-7 human breast cancer cellsBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2002Valérie Chopin This study was performed to determine the effect and action mechanisms of sodium butyrate (NaB) on the growth of breast cancer cells. Butyrate inhibited the growth of all breast cancer cell lines analysed. It induced cell cycle arrest in G1 and apoptosis in MCF-7, MCF-7ras, T47-D, and BT-20 cells, as well as arrest in G2/M in MDA-MB-231 cells. Transient transfection of MCF-7 and T47-D cells with wild-type and antisense p53 did not modify butyrate-induced apoptosis. Pifithrin-,, which inhibits the transcriptional activity of P53, did not modify cell growth or apoptosis of MCF-7 and T47-D cells treated with butyrate. These results indicate that P53 was not involved in butyrate-induced growth inhibition of breast cancer cells. Treatment of MCF-7 cells with anti-Fas agonist antibody induced cell death, indicating that Fas was functional in these cells. Moreover, butyrate potentiated Fas-induced apoptosis, as massive apoptosis was observed rapidly when MCF-7 cells were treated with butyrate and anti-Fas agonist antibody. In addition, butyrate-induced apoptosis in MCF-7 cells was considerably reduced by anti-Fas antagonist antibody. Western blot analysis showed that butyrate increased Fas and Fas ligand levels (Fas L), indicating that butyrate-induced apoptosis may be mediated by Fas signalling. These results demonstrate that butyrate inhibited the growth of breast cancer cells in a P53-independent manner. Moreover, it induced apoptosis via the Fas/Fas L system and potentiated Fas-triggered apoptosis in MCF-7 cells. These findings may open interesting perspectives in human breast cancer treatment strategy. British Journal of Pharmacology (2002) 135, 79,86; doi:10.1038/sj.bjp.0704456 [source] | ||||||||||||||||