共查询到20条相似文献,搜索用时 31 毫秒
1.
Max Shpak Luciana Girotto Gentil Manuel Miranda 《Journal of molecular evolution》2014,78(3-4):188-193
In the vertebrate central nervous system, glycinergic neurotransmission is regulated by the action of the glycine transporters 1 and 2 (GlyT1 and GlyT2)—members of the solute carrier family 6 (SLC6). Several invertebrate deuterostomes have two paralogous glycine carrier genes, with one gene in the pair having greater sequence identity and higher alignment scores with respect to GlyT1 and the other paralog showing greater similarity to GlyT2. In phylogenetic trees, GlyT2-like sequences from invertebrate deuterostomes form a monophyletic subclade with vertebrate GlyT2, while invertebrate GlyT1-like proteins constitute an outgroup to both the GlyT2-like proteins and to vertebrate GlyT1 sequences. These results are consistent with the hypothesis that vertebrate GlyT1 and GlyT2 are, respectively, derived from GlyT1- and GlyT2-like genes in invertebrate deuterostomes. This implies that the gene duplication which gave rise to these paralogs occurred prior to the origin of vertebrates. GlyT2 subsequently diverged significantly from its invertebrate orthologs (i.e., through the acquisition of a unique N-terminus) as a consequence of functional specialization, being expressed principally in the lower CNS; while GlyT1 has activity in both the lower CNS and several regions of the forebrain. 相似文献
2.
Molecular Evolution and Functional Divergence of the Metallothionein Gene Family in Vertebrates 总被引:1,自引:0,他引:1
Nina Serén Scott Glaberman Miguel A. Carretero Ylenia Chiari 《Journal of molecular evolution》2014,78(3-4):217-233
The metallothionein (MT) gene superfamily consists of metal-binding proteins involved in various metal detoxification and storage mechanisms. The evolution of this gene family in vertebrates has mostly been studied in mammals using sparse taxon or gene sampling. Genomic databases and available data on MT protein function and expression allow a better understanding of the evolution and functional divergence of the different MT types. We recovered 77 MT coding sequences from 20 representative vertebrates with annotated complete genomes. We found multiple MT genes, also in reptiles, which were thought to have only one MT type. Phylogenetic and synteny analyses indicate the existence of a eutherian MT1 and MT2, a tetrapod MT3, an amniote MT4, and fish MT. The optimal gene-tree/species-tree reconciliation analyses identified the best root in the fish clade. Functional analyses reveal variation in hydropathic index among protein domains, likely correlated with their distinct flexibility and metal affinity. Analyses of functional divergence identified amino acid sites correlated with functional divergence among MT types. Uncovering the number of genes and sites possibly correlated with functional divergence will help to design cost-effective MT functional and gene expression studies. This will permit further understanding of the distinct roles and specificity of these proteins and to properly target specific MT for different types of functional studies. Therefore, this work presents a critical background on the molecular evolution and functional divergence of vertebrate MTs to carry out further detailed studies on the relationship between heavy metal metabolism and tolerances among vertebrates. 相似文献
3.
Anke Konrad Jason Lai Zeeshan Mutahir Jure Piškur David A. Liberles 《Journal of molecular evolution》2014,78(3-4):202-216
Deoxyribonucleoside kinases (dNKs) carry out the rate-determining step in the nucleoside salvage pathway within all domains of life where the pathway is present, and, hence, are an indication on whether or not a species/genus retains the ability to salvage deoxyribonucleosides. Here, a phylogenetic tree is constructed for the thymidine kinase 2-like dNK gene family in metazoa. Each enzyme class (deoxycytidine, deoxyguanosine, and deoxythymidine kinases, as well as the multisubstrate dNKs) falls into a monophyletic clade. However, in vertebrates, dCK contains an apparent duplication with one paralog lost in mammals, and a number of crustacean genomes (like Caligus rogercresseyi and Lepeophtheirus salmonis) unexpectedly contain not only the multisubstrate dNKs, related to Drosophila multisubstrate dNK, but also a TK2-like kinase. Additionally, crustaceans (Daphnia, Caligus, and Lepeophtheirus) and some insects (Tribolium, Danaus, Pediculus, and Acyrthosiphon) contain several multisubstrate dNK-like enzymes which group paraphyletically within the arthropod clade. This might suggest that the multisubstrate dNKs underwent multiple rounds of duplications with differential retention of duplicate copies between insect families and more complete retention within some crustaceans and insects. Genomes of several basal animalia contain more than one dNK-like sequence, some of which group outside the remaining eukaryotes (both plants and animals) and/or with bacterial dNKs. Within the vertebrates, the mammalian genomes do not contain the second dCK, while birds, fish, and amphibians do retain it. Phasianidae (chicken and turkey) have lost dGK, while it has been retained in other bird lineages, like zebra finch. Reconstruction of the ancestral sequence between the multisubstrate arthropod dNKs and the TK2 clade of vertebrates followed by homology modeling and discrete molecular dynamics calculations on this sequence were performed to examine the evolutionary path which led to the two different enzyme classes. The structural models showed that the carboxyl terminus of the ancestral sequence is more helical than dNK, in common with TK2, although any implications of this for enzyme specificity will require biochemical validation. Finally, rate-shift and conservation-shift analysis between clades with different specificities uncovered candidate residues outside the active site pocket which may have contributed to differentiation in substrate specificity between enzyme clades. 相似文献
4.
The Evolution of Reproduction-Related NLRP Genes 总被引:1,自引:0,他引:1
NLRP proteins are important components of inflammasomes with a major role in innate immunity. A subset of NLRP genes, with unknown functions, are expressed in oocytes and early embryos. Mutations of Nlrp5 in mice are associated with maternal-effect embryonic lethality and mutations of NLRP7 in women are associated with conception of biparental complete hydatidiform moles (biCHMs), suggesting perturbed processes of genomic imprinting. Recessive mutations on NLRP2/7 in humans are associated with reproductive disorders and appear to be induced by a demethylation of the maternal pronucleus. In this study, we find that radiation of NLRP genes occurred before the common ancestor of Afrotheria and Boreoeutheria, with the clade of oocyte-expressed genes originating before the divergence of marsupial and eutherian mammals. There have been multiple independent duplications of NLRP2 genes one of which produced the NLRP7 gene associated with biCHMs. 相似文献
5.
Abdullah Akpinar Abdülhadi Cihangir Uğuz Mustafa Nazıroğlu 《The Journal of membrane biology》2014,247(5):451-459
Calcium ion (Ca2+) is one of the universal second messengers, which acts in a wide range of cellular processes. Results of recent studies indicated that ROS generated by depression leads to loss of endoplasmic reticulum-Ca2+ homeostasis, oxidative stress, and apoptosis. Agomelatine and duloxetine are novel antidepressant and antioxidant drugs and may reduce oxidative stress, apoptosis, and Ca2+ entry through TRPM2 and voltage-gated calcium channels. We tested the effects of agomelatine, duloxetine, and their combination on oxidative stress, Ca2+ influx, mitochondrial depolarization, apoptosis, and caspase values in the PC-12 neuronal cells. PC-12 neuronal cells were exposed in cell culture and exposed to appropriate non-toxic concentrations and incubation times for agomelatine were determined in the neurons by assessing cell viability. Then PC-12 cells were incubated with agomelatine and duloxetine for 24 h. Treatment of cultured PC-12 cells with agomelatine, duloxetine, and their combination results in a protection on apoptosis, caspase-3, caspase-9, mitochondrial membrane depolarization, cytosolic ROS production, glutathione peroxidase, reduced glutathione, and lipid peroxidation, values. Ca2+ entry through non-specific TRPM2 channel blocker (2-APB) and voltage-gated Ca2+ channel blockers (verapamil and diltiazem) was modulated by agomelatine and duloxetine. However, effects of duloxetine on the Ca2+ entry through TRPM2 channels were higher than in agomelatine. Results of current study suggest that the agomelatine and duloxetine are useful against apoptotic cell death and oxidative stress in PC-12 cells, which seem to be dependent on mitochondrial damage and increased levels of intracellular Ca2+ through activation of TRPM2 and voltage-gated Ca2+ channels. 相似文献
6.
Yuan Zhou Xuewei Chen Xiao Liu Hujie Lu Ying Li Hui Zhu Gaihong An Na Zhang Jianning Zhang Qiang Ma Yanjun Zhang 《The Journal of membrane biology》2014,247(6):461-468
Involvement of phosphoinositide 3-kinases (PI3Ks) in early aldosterone action on epithelial sodium channel (ENaC) in mammalian renal epithelia was investigated by hopping probe ion conductance microscopy combined with patch-clamping in this study. Aldosterone treatment enlarged the cell volume and elevated the apical membrane of renal mpkCCDc14 epithelia, which resulted in enhancing the open probability of ENaC. Inhibition of PI3K pathway by LY294002 obviously suppressed these aldosterone-induced changes in both cell morphology and ENaC activity. These results indicated the important role of PI3K pathway in early aldosterone action and the close relationship between cell morphology and ENaC activity in mammalian renal epithelia. 相似文献
7.
Yuchan Zhou Xiaoping Pan Hongxia Qu Steven J. R. Underhill 《The Journal of membrane biology》2014,247(5):429-439
Vacuole represents a major storage organelle playing vital roles in pH homoeostasis and cellular detoxification. The chemical and functional properties of tonoplast in response to chilling temperature and their roles in chilling injury are largely unknown. In the current study, lipid composition of tonoplast and the activities of two vacuolar proton pumps, H+-ATPase (V-ATPase) and H+-pyrophosphatase (V-PPase), were investigated in accordance with the development of blackheart, a form of chilling injury in pineapple fruit (Ananas comosus). Chilling temperature at 10 °C for 1 week induced irreversible blackheart injury in concurrence with a substantial decrease in V-ATPase activity. By contrast, the activity was increased after 1 week at 25 °C. The activity of V-PPase was not changed under both temperatures. Level of total phospholipids of tonoplast decreased at 10 °C, but increased at 25 °C. There was no change at the level of total glycolipids under both temperatures. Thus, low temperature increased the ratio of total glycolipids vs. total phospholipids of tonoplast. Phosphatidylcholine and phosphatidylethanolamine were the predominant phospholipids of tonoplast. Low temperature increased the relative level of phosphatidic acid but decreased the percentage of both phosphatidylcholine and phosphatidylethanolamine. Unsaturated fatty acids accounted for over 60 % of the total tonoplast fatty acids, with C18:1 and C18:2 being predominant. Low temperature significantly decreased the percentage of C18:3. Modification of membrane lipid composition and its effect on the functional property of tonoplast at low temperature were discussed in correlation with their roles in the development of chilling injury in pineapple fruit. 相似文献
8.
David E. Nix 《Current fungal infection reports》2014,8(2):129-138
This review addresses the potential of antifungal drugs to cause cardiac toxicity. Many antifungal drugs, especially antifungal azoles, rarely cause torsades de pointes (TdP) and carry the risk of sudden death. Interventions to avoid TdP should include cautious use of azoles in combination with other drugs that cause QTc prolongation, and elimination of risk factors for TdP whenever possible. These risk factors include: hypokalemia, hypomagnesemia, severe bradycardia, and preexisting long QT syndrome. ECG monitoring should be considered when the use of multiple QT-prolonging drugs is unavoidable and TdP risk factors cannot be resolved. Itraconazole exhibits negative inotropic activity which may present as worsening heart failure in patients with preexisting heart failure. A few cases of severe bradycardia have also been described with voriconazole. Most cases of cardiac toxicity associated with amphotericin B are due to severe electrolyte abnormalities, rapid administration or overdose. Although cardiac toxicity is not common with the use of antifungal drugs, recognition of the potential to cause serious cardiac-related outcomes, evaluation of risk factors, and monitoring is warranted. 相似文献
9.
The total curative dose of amphotericin B for any given fungal infection or specific patient is not precisely known. Prior to the availability of lipid formulations of amphotericin B (LFAB), dosing of amphotericin B was dictated by its associated toxicity. The unique pharmacokinetic features of each LFAB have led to differences in their recommended doses. Most published data have evaluated doses of 3–5 mg/kg/day, although niches exist for both higher and lower doses. Low-dose LFAB allows for intravenous broad-spectrum antifungal coverage without drug-drug interactions and with reduced toxicity. High-dose LFAB demonstrates increased fungal clearance in animal models, although this has not translated to improved clinical outcomes for most invasive fungal infections. Although available data do not demonstrate significant benefit associated with high-dose therapy, for liposomal amphotericin B, the data also demonstrate no significant harm. As such, the use of high-dose liposomal amphotericin B for salvage therapy may be a consideration. 相似文献
10.
Masa Bosnjak Beatriz Canals Lorente Ziva Pogacar Vesna Makovsek Maja Cemazar 《The Journal of membrane biology》2014,247(5):421-428
Electroporation as a delivery method is increasingly important in gene therapy, not only in vivo but also in in vitro experimental systems. Different applications of gene electrotransfer require high viability of cells and high transfection efficiency of gene electrotransfer. It was already demonstrated that the addition of fetal bovine serum (FBS) immediately after gene electrotransfer leads to improved cell survival and transfection efficiency. Therefore, the aim of the study was to determine whether prolonged incubation of cells in FBS, for more than standard 5 min, can lead to increased transfection efficiency and improved cell survival. Different murine melanoma and murine and human endothelial cell lines were transfected with plasmid encoding green fluorescent protein and then incubated for different periods of time in FBS (5–30 min). Transfection efficiency was determined by flow cytometry and fluorescence microscopy and cell survival by cell viability assay. Prolonged incubation of cells in FBS after gene electrotransfer had varying effect on cell survival, which was decreased in melanoma cell lines B16F1 and B16F10, minimally affected in SVEC4-10 and HUVEC cells and increased in 2H11 cell at 30 min of incubation time in FBS. On the other hand, transfection efficiency of gene electrotransfer was not affected by long incubation of cell in FBS, regardless of the cell line used. The results of our study emphasize the importance of optimization of gene electrotransfer protocol for particular cells and specific purposes of gene electrotransfer, taking into account the importance of transfection efficiency and cell survival. 相似文献
11.
Anja Forche 《Current fungal infection reports》2014,8(2):163-170
Pathogenic fungi encounter many different host environments to which they must adapt rapidly to ensure growth and survival. They also must be able to cope with alterations in established niches during long-term persistence in the host. Many eukaryotic pathogens have evolved a highly plastic genome, and large-scale chromosomal changes including aneuploidy, and loss of heterozygosity (LOH) can arise under various in vitro and in vivo stresses. Both aneuploidy and LOH can arise quickly during a single cell cycle, and it is hypothesized that they provide a rapid, albeit imprecise, solution to adaptation to stress until better and more refined solutions can be acquired by the organism. While LOH, with the extreme case of haploidization in Candida albicans, can purge the genome from recessive lethal alleles and/or generate recombinant progeny with increased fitness, aneuploidy, in the absence or rarity of meiosis, can serve as a non-Mendelian mechanism for generating genomic variation. 相似文献
12.
Supercritical CO2 Induces Marked Changes in Membrane Phospholipids Composition in Escherichia coli K12 总被引:1,自引:0,他引:1
Sabrina Tamburini Andrea Anesi Giovanna Ferrentino Sara Spilimbergo Graziano Guella Olivier Jousson 《The Journal of membrane biology》2014,247(6):469-477
Supercritical carbon dioxide (SC-CO2) treatment is one of the most promising alternative techniques for pasteurization of both liquid and solid food products. The inhibitory effect of SC-CO2 on bacterial growth has been investigated in different species, but the precise mechanism of action remains unknown. Membrane permeabilization has been proposed to be the first event in SC-CO2-mediated inactivation. Flow cytometry, high performance liquid chromatography–electrospray ionization–mass spectrometry and NMR analyses were performed to investigate the effect of SC-CO2 treatment on membrane lipid profile and membrane permeability in Escherichia coli K12. After 15 min of SC-CO2 treatment at 120 bar and 35 °C, the majority of bacterial cells dissipated their membrane potential (95 %) and lost membrane integrity, as 81 % become partially permeabilized and 18 % fully permeabilized. Membrane permeabilization was associated with a 20 % decrease in bacterial biovolume and to a strong (>50 %) reduction in phosphatidylglycerol (PG) membrane lipids, without altering the fatty acid composition and the degree of unsaturation of acyl chains. PGs are thought to play an important role in membrane stability, by reducing motion of phosphatidylethanolamine (PE) along the membrane bilayer, therefore promoting the formation of inter-lipid hydrogen bonds. In addition, the decrease in intracellular pH induced by SC-CO2 likely alters the chemical properties of phospholipids and the PE/PG ratio. Biophysical effects of SC-CO2 thus cause a strong perturbation of membrane architecture in E. coli, and such alterations are likely associated with its strong inactivation effect. 相似文献
13.
Naomi R. Latorraca Keith M. Callenberg Jon P. Boyle Michael Grabe 《The Journal of membrane biology》2014,247(5):395-408
Experimental and computational studies have shown that cellular membranes deform to stabilize the inclusion of transmembrane (TM) proteins harboring charge. Recent analysis suggests that membrane bending helps to expose charged and polar residues to the aqueous environment and polar head groups. We previously used elasticity theory to identify membrane distortions that minimize the insertion of charged TM peptides into the membrane. Here, we extend our work by showing that it also provides a novel, computationally efficient method for exploring the energetics of ion and small peptide penetration into membranes. First, we show that the continuum method accurately reproduces energy profiles and membrane shapes generated from molecular simulations of bare ion permeation at a fraction of the computational cost. Next, we demonstrate that the dependence of the ion insertion energy on the membrane thickness arises primarily from the elastic properties of the membrane. Moreover, the continuum model readily provides a free energy decomposition into components not easily determined from molecular dynamics. Finally, we show that the energetics of membrane deformation strongly depend on membrane patch size both for ions and peptides. This dependence is particularly strong for peptides based on simulations of a known amphipathic, membrane binding peptide from the human pathogen Toxoplasma gondii. In total, we address shortcomings and advantages that arise from using a variety of computational methods in distinct biological contexts. 相似文献
14.
Varalakshmi Durairaj Garima Shakya Sankar Pajaniradje Rukkumani Rajagopalan 《The Journal of membrane biology》2014,247(6):515-521
Alcoholism is a broad term used for problems related to alcohol, medically considered as disease, specifically an addictive illness, abuse, and dependence. It is the major cause of liver disease in western countries. Alcoholic liver disease encompasses the hepatic alterations leading to fatty liver, hepatitis, and fibrosis or cirrhosis. Fried food items prepared with repeatedly heated polyunsaturated fatty acid (PUFA) exacerbate the disturbances induced by alcohol. The use of herbs to treat diseases is almost universal. Wheatgrass (WG) is used as a supplemental nutrition because of its unique curative properties. As it has antioxidant property, it prevents cancer, diabetes, and acts as liver cleanser. The present study was undertaken to evaluate the efficacy of WG on preserving membrane integrity in liver damage induced by alcohol and heated PUFA (ΔPUFA).The rats were divided into four groups. The animals in group 1 served as normal (standard diet), group 2 served as hepatotoxic (alcohol + ΔPUFA), group 3 served as treated (alcohol + ΔPUFA + WG), and group 4 served as WG control. The compositions of membrane fatty acid, total phospholipids, phospholipase A, C (PLA and PLC) were analyzed in liver to evaluate the effects of WG. Changes in fatty acid composition, decrease in phospholipids levels, and increase in PLA, PLC were observed in the diseased group. Restoration effect was seen in WG-treated rats. Histopathological observations were in correlation with the biochemical parameters. From the results obtained, we conclude that WG effectively protects the liver against alcohol and ΔPUFA-induced changes in fatty acid composition and preserves membrane integrity. 相似文献
15.
Elizabeth Erickson Levendoski M. Preeti Sivasankar 《The Journal of membrane biology》2014,247(5):441-450
The vocal fold epithelium is exposed to inhaled particulates including pollutants during breathing in everyday environments. Yet, our understanding of the effects of pollutants on vocal fold epithelial function is extremely limited. The objective of this study was to investigate the effect of the pollutant acrolein on two vocal fold epithelial mechanisms: ion transport and mucin (MUC) synthesis. These mechanisms were chosen as each plays a critical role in vocal defense and in maintaining surface hydration which is necessary for optimal voice production. Healthy, native porcine vocal folds (N = 85) were excised and exposed to an acrolein or sham challenge. A 60-min acrolein, but not sham challenge significantly reduced ion transport and inhibited cyclic adenosine monophosphate-dependent, increases in ion transport. Decreases in ion transport were associated with reduced sodium absorption. Within the same timeline, no significant acrolein-induced changes in MUC gene or protein expression were observed. These results improve our understanding of the effects of acrolein on key vocal fold epithelial functions and inform the development of future investigations that seek to elucidate the impact of a wide range of pollutant exposures on vocal fold health. 相似文献
16.
Carlos Manlio Diaz-Garcia Sara L. Morales-Lázaro Carmen Sánchez-Soto Myrian Velasco Tamara Rosenbaum Marcia Hiriart 《The Journal of membrane biology》2014,247(6):479-491
Transient receptor potential channels have been put forward as regulators of insulin secretion. A role for the TRPV1 ion channel in insulin secretion has been suggested in pancreatic beta cell lines. We explored whether TRPV1 is functionally expressed in RINm5F and primary beta cells from neonate and adult rats. We examined if capsaicin could activate cationic non-selective currents. Our results show that TRPV1 channels are not functional in insulin-secreting cells, since capsaicin did not produce current activation, not even under culture conditions known to induce the expression of other ion channels in these cells. Although TRPV1 channels seem to be irrelevant for the physiology of isolated beta cells, they may play a role in glucose homeostasis acting through the nerve fibers that regulate islet function. At the physiological level, we observed that Trpv1 ?/? mice presented lower fasting insulin levels than their wild-type littermates, however, we did not find differences between these experimental groups nor in the glucose tolerance test or in the insulin secretion. However, we did find that the Trpv1 ?/? mice exhibited a higher insulin sensitivity compared to their wild-type counterparts. Our results demonstrate that TRPV1 does not contribute to glucose-induced insulin secretion in beta cells as was previously thought, but it is possible that it may control insulin sensitivity. 相似文献
17.
18.
Ch. Sultan J. M. Lobaccaro S. Lumbroso S. Missov Ch. Belon M. Bost R. Dumas 《Andrologie》1994,4(3):283-287
Klinfelter syndrome was first described in adult males with gynecomastia, azoospermia and hypergonadotropic hypogonadism. Children with the 47, XXY karyotype demonstrate few clinical findings so Klinefelter syndrome is rarely diagnosed until adult life. Besides children who have been diagnosed during prenatal genetic testing, in infancy a male with 47, XXY (or variants: 46, XY-47, XXY; 48, XXXY; 48, XXYY, 49, XXXXY) may be found while undergoing evaluation of micropenis, hypospadias, cryptorchidism or facial anomalies. The older child may present with learning disabilities, behavior disorders or tall stature. At the time of puberty, the clinical picture includes small testes, gynecomastia and an eunuchoid habitus. Early diagnosis of Klinefelter syndrome must be performed since it has been demonstrated that early treatment with androgens may ameliorate many aspects of the clinical symptoms and attenuate or prevent behavioral and psychiatric disorders associated with 47, XXY males. 相似文献
19.
Craig A. Cooney 《Molecular biotechnology》1994,2(2):119-127
High resolution DNA size markers are described for pulsed field gel electrophoresis (PFGE). These markers provide resolution of 10–20 kbp over a size range from 10 kbp to more than 400 kbp and are produced by partial restriction digestion of lambda phage DNA concatemers (λ ladder). High resolution markers extending to over 400 kbp are made by partial restriction digestion of λ ladder embedded in agarose. Detailed methods are described for marker production and for DNA separation by contour-clamped homogeneous electric field (CHEF) electrophoresis. These markers and methods are useful for a variety of high resolution DNA mapping by PFGE. 相似文献
20.
Jamshed Warsi Bernat Elvira Zohreh Hosseinzadeh Ekaterina Shumilina Florian Lang 《The Journal of membrane biology》2014,247(5):387-393
Janus kinase-3 (JAK3) fosters proliferation and counteracts apoptosis of lymphocytes and tumor cells. The gain of function mutation A572VJAK3 has been discovered in acute megakaryoplastic leukemia. JAK3 is inactivated by replacement of lysine by alanine in the catalytic subunit (K855AJAK3). Regulation of cell proliferation and apoptosis involves altered activity of Cl? channels. The present study, thus, explored whether JAK3 modifies the function of the small conductance Cl? channel ClC-2. To this end, ClC-2 was expressed in Xenopus oocytes with or without wild-type JAK3, A568VJAK3 or K851AJAK3, and the Cl? channel activity determined by dual-electrode voltage clamp. Channel protein abundance in the cell membrane was determined utilizing chemiluminescence. As a result, expression of ClC-2 was followed by a marked increase of cell membrane conductance. The conductance was significantly decreased following coexpression of JAK3 or A568VJAK3, but not by coexpression of K851AJAK3. Exposure of the oocytes expressing ClC-2 together with A568VJAK3 to the JAK3 inhibitor WHI-P154 (4-[(3’-bromo-4’-hydroxyphenyl)amino]-6,7-dimethoxyquinazoline, 22 μM) increased the conductance. Coexpression of A568VJAK3 decreased the ClC-2 protein abundance in the cell membrane of ClC-2 expressing oocytes. The decline of conductance in ClC-2 and A568VJAK3 coexpressing oocytes following inhibition of channel protein insertion by brefeldin A (5 μM) was similar in oocytes expressing ClC-2 with A568VJAK3 and oocytes expressing ClC-2 alone, indicating that A568VJAK3 might slow channel protein insertion into rather than accelerating channel protein retrieval from the cell membrane. In conclusion, JAK3 downregulates ClC-2 activity and thus counteracts Cl? exit—an effect possibly influencing cell proliferation and apoptosis. 相似文献