Physiological significance of delayed rectifier K+ channels (Kv1.3) expressed in T lymphocytes and their pathological significance in chronic kidney disease

Kazama, Itsuro

doi:10.1007/s12576-014-0331-x

Cited by 28 publications

(51 citation statements)

References 105 publications

(105 reference statements)

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“…Lymphocyte activation is closely associated with K + channels on the lymphocyte membrane. K + channels function in controlling membrane potential, regulating cell volume and activating lymphocytes (31,32); therefore, they have an important role in the process of lymphocyte immunity. The present study investigated the current characteristics of voltage-dependent K + channels (K v ) and Ca 2+ -activated K + channels (K Ca ) in Jurkat T cells.…”

Section: Discussionmentioning

confidence: 99%

Effect of lysophosphatidic acid on the immune inflammatory response and the connexin 43 protein in myocardial infarction

Zhang

Zhao

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Lysophosphatidic acid (LPA) is an intermediate product of membrane phospholipid metabolism. Recently, LPA has gained attention for its involvement in the pathological processes of certain cardiovascular diseases. The aim of the present study was to clarify the association between the effect of LPA and the immune inflammatory response, and to investigate the effects of LPA on the protein expression levels of connexin 43 during myocardial infarction. Surface electrocardiograms of myocardial infarction rats and isolated rat heart tissue samples were obtained in order to determine the effect of LPA on the incidence of arrhythmia in rats that exhibited changes in immune status. The results demonstrated that the incidence of arrhythmia decreased when the rat immune systems were suppressed, and the incidence of arrhythmia increased when the rat immune systems were enhanced. The concentration levels of tumor necrosis factor (TNF)-α were determined by ELISA, and the results demonstrated that LPA induced T lymphocyte synthesis and TNF-α release. Using a patch-clamp technique, LPA was shown to increase the current amplitude of the voltage-dependent potassium channels (K v ) and calcium-activated potassium channels (K Ca ) in Jurkat T cells. The protein expression of connexin 43 (Cx43) was determined by immunohistochemical staining. The results indicated that LPA caused the degradation of Cx43 and decreased the expression of Cx43. This effect was associated with the immune status of the rats. There was a further decrease in Cx43 expression in the rats of the immune-enhanced group. To the best of our knowledge, these results provide the first evidence that LPA causes arrhythmia through the regulation of immune inflammatory cells and the decrease of Cx43 protein expression. The present study provided an experimental basis for the treatment of arrhythmia and may guide clinical care. IntroductionAcute myocardial infarction (AMI) is a disease that severely affects the health and life quality of patients. Arrhythmia is a complication of myocardial infarction, which is one of the most severe cardiovascular diseases, and it is the predominant cause of myocardial infarction-associated mortality (1). Since patients with ischemic heart disease are particularly prone to arrhythmias, they are often admitted for arrhythmia monitoring (2). Lysophosphatidic acid (LPA), which is an intermediate product of membrane phospholipid metabolism, is a lipid mediator with various biological functions that are predominantly mediated by specific G protein-coupled receptors (3). As a water-soluble glycerol phospholipid with a simple structure, LPA is secreted from numerous cell types, including platelets, fibroblasts and ovarian cancer cells (4). The concentration of LPA in regional myocardial tissue and plasma increases during myocardial infarction, and it can also cause arrhythmia (5).During myocardial infarction, both the infarcted area and the non-infarcted area exhibit perivasculitis, and the infiltration of a large number of inflammator...

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Section: Discussionmentioning

confidence: 99%

Effect of lysophosphatidic acid on the immune inflammatory response and the connexin 43 protein in myocardial infarction

Zhang

Zhao

et al. 2016

Experimental and Therapeutic Medicine

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“…concentration stimulate the following Ca 2? signaling pathway necessary to trigger the lymphocyte activation and proliferation, and thus activate cellular immunity [73]. Regarding the molecular mechanisms that mediate the signaling pathway, the rise in the intracellular Ca 2?…”

Section: Lymphocyte Kv13-channels In Cellular Immunitymentioning

confidence: 99%

“…Modified from Ref. [31] Usefulness of targeting lymphocyte Kv1.3-channels in the treatment… activated T cells (NFAT), enabling it to accumulate in the nucleus and bind to the promoter of the gene encoding IL-2 [30,73]. Various kinds of immunosuppressive reagents, which target these signaling molecules, such as cyclosporine and tacrolimus (FK506), have been developed, and most of these are now commonly used in the clinical practice [74].…”

Section: Lymphocyte Kv13-channels In Cellular Immunitymentioning

confidence: 99%

“…Additionally, infectious diseases and autoimmune disorders, including a number of diseases such as cancer, neuroinflammatory diseases, metabolic disorders, and chronic kidney disease (CKD), nowadays fall into this category [73,77]. In previous studies, the overexpression of Kv1.3-channels was demonstrated in cells under such pathologic conditions, including cancer [78,79], ischemic heart disease [80], and autoimmune disorders [81,82].…”

Section: Targeting Lymphocyte Kv13 In ''Chronic Inflammatory Diseases''mentioning

confidence: 99%

“…Therefore, the membrane surface area (A) of thymocytes was not likely to change by the application of azithromycin. In this context, assuming that e and A are relatively constant before and after the drug application, the increase in d is considered to be responsible for the decrease in Cm [73,116]. Since azithromycin is much more lipophilic than clarithromycin [117,118], it would disperse more easily into the lipid bilayers of the plasma membrane.…”

Section: Immunomodulation By Clarithromycin As a Potent Kv13-channelmentioning

confidence: 99%

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Usefulness of targeting lymphocyte Kv1.3-channels in the treatment of respiratory diseases

2015

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T lymphocytes predominantly express delayed rectifier K(+)-channels (Kv1.3) in their plasma membranes. Patch-clamp studies revealed that the channels play crucial roles in facilitating the calcium influx necessary to trigger lymphocyte activation and proliferation. Using selective channel inhibitors in experimental animal models, in vivo studies further revealed the clinically relevant relationship between the channel expression and the development of chronic respiratory diseases, in which chronic inflammation or the overstimulation of cellular immunity in the airways is responsible for the pathogenesis. In chronic respiratory diseases, such as chronic obstructive pulmonary disease, asthma, diffuse panbronchiolitis and cystic fibrosis, in addition to the supportive management for the symptoms, the anti-inflammatory effects of macrolide antibiotics were shown to be effective against the over-activation or proliferation of T lymphocytes. Recently, we provided physiological and pharmacological evidence that macrolide antibiotics, together with calcium channel blockers, HMG-CoA reductase inhibitors, and nonsteroidal anti-inflammatory drugs, effectively suppress the Kv1.3-channel currents in lymphocytes, and thus exert anti-inflammatory or immunomodulatory effects. In this review article, based on the findings obtained from recent in vivo and in vitro studies, we address the novel therapeutic implications of targeting the lymphocyte Kv1.3-channels for the treatment of chronic or acute respiratory diseases.

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9,9-Diaryl-4,5-diazafluorene-based Cardo polymer; Synthesis and characteristic properties

Okuda

Koyama

Kojima

et al. 2013

J. Polym. Sci. Part A: Polym. Chem.

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To open out new aspects of 9,9-diarylfluorene (DAF)-based polymers with high performances, 9,9-(4-hydroxyphenyl)-4,5-diazafluorene (N-BPF) was designed as a new cardo structure and the properties of poly(ether ketone)s (N-PEKs) containing N-BPF skeletons were examined in detail. N-PEKs were synthesized in high yields via polycondensation of N-BPF with difluoroarenes. N-PEKs showed cardo polymer-specific properties such as high thermal stability and high solubility in organic solvents. The addition of p-toluenesulfonic acid (TsOH) to N-PEK resulted in the formation of network polymer based on interchain hydrogen bonds. It turned out that the films of network polymer are flexible and transparent and exhibit high refractive index and low birefringence. The effects of feed ratio of TsOH to N-PEK were also evaluated on the mechanical properties of network polymer.

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Physiological significance of delayed rectifier K+ channels (Kv1.3) expressed in T lymphocytes and their pathological significance in chronic kidney disease

Cited by 28 publications

References 105 publications

Effect of lysophosphatidic acid on the immune inflammatory response and the connexin 43 protein in myocardial infarction

Effect of lysophosphatidic acid on the immune inflammatory response and the connexin 43 protein in myocardial infarction

Usefulness of targeting lymphocyte Kv1.3-channels in the treatment of respiratory diseases

9,9-Diaryl-4,5-diazafluorene-based Cardo polymer; Synthesis and characteristic properties

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