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Chunling Huang, Ling Zhang, Ying Shi, Hao Yi, Yongli Zhao, Jason Chen, Carol A Pollock, Xin-Ming Chen
Despite optimal control of hyperglycaemia, hypertension, and dyslipidaemia, the number of patients with diabetic nephropathy (DN) continues to grow. Strategies to target various signaling pathways to prevent DN have been intensively investigated in animal models and many have been proved to be promising. However, targeting these pathways once kidney disease is established, remain unsatisfactory. The clinical scenario is that patients with diabetes mellitus often present with established kidney damage and need effective treatments to repair and reverse the kidney damage...
2018: PloS One
Hui Li, Jun-Ling Zhao, Yuan-Ming Zhang, Su-Xia Han
BACKGROUND AND AIM: Increasing evidence confirms that potassium channels are essential for lymphocyte activation, suggesting an involvement in the development of hypertension. Moreover, chronic inflammation is regarded as a direct or indirect manifestation of hypertension, highlighting the theoretical mechanisms. In this study, we investigated changes in KCa3.1 potassium channel expression in the blood of hypertensive and healthy Kazakh people in north-west China. METHODS: Flow cytometry technology was used for T-lymphocyte subtype analysis...
February 1, 2018: Clinical and Experimental Hypertension: CHE
Yotesawee Srisomboon, Nathan A Zaidman, Peter J Maniak, Chatsri Deachapunya, Scott M O'Grady
The objective of this study was to determine the molecular identity of ion channels involved in K+ secretion by the mammary epithelium and to examine their regulation by purinoceptor agonists. Apical membrane voltage clamp experiments were performed on human mammary epithelial cells where the basolateral membrane was exposed to the pore-forming antibiotic amphotericin B dissolved in a solution with intracellular-like ionic composition. Addition of the Na+ channel inhibitor benzamil reduced the basal current, consistent with inhibition of Na+ uptake across the apical membrane whereas the KCa 3...
January 24, 2018: American Journal of Physiology. Cell Physiology
Etmar Bulk, Nadzeya Kramko, Ivan Liashkovich, Felix Glaser, Hermann Schillers, Hans-Joachim Schnittler, Hans Oberleithner, Albrecht Schwab
Early metastasis leads to poor prognosis of lung cancer patients, whose 5-year survival rate is only 15%. We could recently show that the Ca2+ sensitive K+ channel KCa3.1 promotes aggressive behavior of non-small cell lung cancer (NSCLC) cells and that it can serve as a prognostic marker in NSCLC. Since NSCLC patients die of metastases, we investigated whether KCa3.1 channels contribute to poor patient prognosis by regulating distinct steps of the metastatic cascade. We investigated the extravasation of NSCLC cells and focused on their adhesion to endothelial cells and on transendothelial migration...
December 22, 2017: Oncotarget
Shinkyu Choi, Ji Aee Kim, Hai-Yan Li, Sae-Jin Lee, Ye Seon Seok, Tae Hun Kim, Ki-Hwan Han, Mi Hye Park, Geum Joon Cho, Suk Hyo Suh
AIMS: Altered redox state has been related to the development of normal pregnancy (NP) and preeclampsia (PE). Endothelial KCa2.3 and KCa3.1 (KCas) play an important role in vasodilation, and KCas levels are affected by oxidative stress. We investigated the mechanisms of oxidative stress-mediated KCas expression modulation during NP and PE. RESULTS: Human uterine microvascular endothelial cells were incubated in serum from normal non-pregnant women (n=13) and women with NP (n=24) or PE (n=15), or in VEGF, oxidized low-density lipoprotein (ox-LDL), progesterone, or estradiol-17-containing medium for 24 hours...
January 15, 2018: Antioxidants & Redox Signaling
Katy M Roach, Amanda Sutcliffe, Laura Matthews, Gill Elliott, Chris Newby, Yassine Amrani, Peter Bradding
Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with limited therapeutic options. KCa3.1 ion channels play a critical role in TGFβ1-dependent pro-fibrotic responses in human lung myofibroblasts. We aimed to develop a human lung parenchymal model of fibrogenesis and test the efficacy of the selective KCa3.1 blocker senicapoc. 2 mm3 pieces of human lung parenchyma were cultured for 7 days in DMEM ± TGFβ1 (10 ng/ml) and pro-fibrotic pathways examined by RT-PCR, immunohistochemistry and collagen secretion...
January 10, 2018: Scientific Reports
Eva M Grössinger, Mincheol Kang, Laura Bouchareychas, Ritu Sarin, Dominik R Haudenschild, Laura N Borodinsky, Iannis E Adamopoulos
In inflammatory arthritis, the dysregulation of osteoclast activity by proinflammatory cytokines, including TNF, interferes with bone remodeling during inflammation through Ca2+-dependent mechanisms causing pathological bone loss. Ca2+-dependent CREB/c-fos activation via Ca2+-calmodulin kinase IV (CaMKIV) induces transcriptional regulation of osteoclast-specific genes via NFATc1, which facilitate bone resorption. In leukocytes, Ca2+ regulation of NFAT-dependent gene expression oftentimes involves the activity of the Ca2+-activated K+ channel KCa3...
December 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
Govindaraj Anumanthan, Philip J Wilson, Ratnakar Tripathi, Nathan P Hesemann, Rajiv R Mohan
Postoperative conjunctival fibrosis is common in patients after glaucoma filtration surgery. The calcium activated potassium (KCa3.1) channel has been shown to inhibit fibrosis in many non-ocular tissues. However, its potential in treating ocular fibrosis remains unknown. We tested the anti-fibrotic potential of TRAM34, a selective blocker of KCa3.1 channel, in treating conjunctival fibrosis. Primary human conjunctival fibroblast (HCF) cultures derived from donor tissues. Myofibroblasts causing conjunctival fibrosis were generated by growing HCFs in the presence of TGFβ1 for 72 h...
December 11, 2017: Experimental Eye Research
Yoshihiro Ishida, Atsushi Otsuka, Kenji Kabashima
PURPOSE OF REVIEW: The present review aims to provide readers with the latest updates on the biology and clinical management of cutaneous angiosarcoma (cAS). RECENT FINDINGS: The genomic alteration of cAS is heterogeneous. Mutations are enriched in the mitosis-activated kinase (MAPK) pathway. Functional analysis has identified molecules that may serve as potential markers and therapeutic targets of angiosarcoma. These molecules include survivin, HSP90, FOXM1, miR-497-5p, KCa3...
March 2018: Current Opinion in Oncology
Peng Dong, Minglong Liu, Chaofeng Liu
Background: KCa 3.1 ion channels play an important role during atherosclerosis. We aimed to investigate the effect of exenatide on KCa 3.1 expression in aortic vascular smooth muscle cells (VSMCs) of diabetic rats. Methods: Sprague-Dawley rats were randomly divided into normal control (NC), diabetes model (DM), and exenatide treatment (ET) groups. Hematoxylin and eosin and α-actin immunohistochemical staining were used to detect changes in rat aortic vascular smooth muscle...
November 2017: Acta Cardiologica Sinica
Serena Pillozzi, Massimo D'Amico, Gianluca Bartoli, Luca Gasparoli, Giulia Petroni, Olivia Crociani, Tiziano Marzo, Angela Guerriero, Luigi Messori, Mirko Severi, Roberto Udisti, Heike Wulff, K George Chandy, Andrea Becchetti, Annarosa Arcangeli
BACKGROUND: Platinum-based drugs such as Cisplatin are commonly employed for cancer treatment. Despite an initial therapeutic response, Cisplatin treatment often results in the development of chemoresistance. To identify novel approaches to overcome Cisplatin resistance, we tested Cisplatin in combination with K(+) channel modulators on colorectal cancer (CRC) cells. METHODS: The functional expression of Ca(2+)-activated (KCa3.1, also known as KCNN4) and voltage-dependent (Kv11...
November 21, 2017: British Journal of Cancer
Olga Karpińska, Marta Baranowska-Kuczko, Barbara Malinowska, Monika Kloza, Magdalena Kusaczuk, Agnieszka Gęgotek, Paweł Golec, Irena Kasacka, Hanna Kozłowska
AIMS: l-Alpha-lysophosphatidylinositol (LPI) is an endogenous agonist of G protein-coupled receptor 55 (GPR55) which relaxes mesenteric arteries on activation. The aim of the present study was to determine the influence and underlying mechanisms of LPI-induced relaxation in human pulmonary arteries (hPAs). MAIN METHODS: Functional studies were performed in isolated hPAs using organ bath technique. The expression of GPR55 in hPAs and bronchioles was determined by real-time qPCR, Western blot analysis, and immunohistochemistry...
November 16, 2017: Life Sciences
Zuheng Ma, Anneli Björklund, Md Shahidul Islam
Pancreatic β-cells express several ion channels of the transient receptor potential family, which play important roles in mediating the stimulus-secretion coupling. One of these channels, the TRPM4 is a Ca(2+)-activated monovalent cation channel. This channel is inhibited by 9-phenanthrol, which also inhibits the TMEM16a Cl(-) channel, and activates the Ca(2+)-activated K(+) channel, Kca3.1. The net effects of ion-channel modulation by 9-phenantherol on the insulin secretion remain unclear. We tested the effects of 9-phenanthrol on glucose- and GLP-1-induced insulin secretion from isolated rat islets in static incubations...
2017: Journal of Diabetes Research
Zhihua Yu, Mengni Yi, Tianjiao Wei, Xiaoling Gao, Hongzhuan Chen
Ischemic stroke is a devastating neurological disease that can initiate a phenotype switch in astrocytes. Reactive astrogliosis is a significant pathological feature of ischemic stroke and is accompanied by changes in gene expression, hypertrophied processes and proliferation. The intermediate-conductance Ca(2+)-activated potassium channel KCa3.1 has been shown to contribute to astrogliosis-induced neuroinflammation in Alzheimer's disease (AD). We here present evidence, from both astrocytes subjected to oxygen-glucose deprivation (OGD) and from the brains of mice subjected to permanent middle cerebral artery occlusion (pMCAO), that KCa3...
2017: Frontiers in Cellular Neuroscience
Giriraj Sahu, Hadhimulya Asmara, Fang-Xiong Zhang, Gerald W Zamponi, Ray W Turner
CaV 1 L-type calcium channels are key to regulating neuronal excitability, with the range of functional roles enhanced by interactions with calmodulin, accessory proteins, or CaMKII that modulate channel activity. In hippocampal pyramidal cells, a prominent elevation of CaV 1 activity is apparent in late channel openings that can last for seconds following a depolarizing stimulus train. The current study tested the hypothesis that a reported interaction among CaV 1.3 channels, the scaffolding protein densin, and CaMKII could generate a facilitation of channel activity that outlasts a depolarizing stimulus...
November 15, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Monika Kloza, Marta Baranowska-Kuczko, Barbara Malinowska, Olga Karpińska, Ewa Harasim-Symbor, Irena Kasacka, Hanna Kozłowska
The aim of this study was to examine the influence of deoxycorticosterone acetate-salt (DOCA-salt) hypertension and chronic treatment with the fatty acid amide hydrolase inhibitor, URB597, on small and intermediate conductance calcium-activated potassium channels and endothelium-dependent hyperpolarization (KCa 2.3/KCa 3.1-EDH) in rat small mesenteric arteries (sMAs). The EDH-type response was investigated, in endothelium-intact sMAs using a wire myograph, by examining acetylcholine-evoked vasorelaxation in the presence of Nω -nitro-L-arginine methyl ester and indomethacin (inhibitors of nitric oxide synthase and cyclooxygenase, respectively)...
December 2017: Vascular Pharmacology
Mengni Yi, Tianjiao Wei, Yanxia Wang, Qin Lu, Gaoxian Chen, Xiaoling Gao, Herbert M Geller, Hongzhuan Chen, Zhihua Yu
BACKGROUND: Reactive astrogliosis is one of the significantly pathological features in ischemic stroke accompanied with changes in gene expression, morphology, and proliferation. KCa3.1 was involved in TGF-β-induced astrogliosis in vitro and also contributed to astrogliosis-mediated neuroinflammation in neurodegeneration disease. METHODS: Wild type mice and KCa3.1-/- mice were subjected to permanent middle cerebral artery occlusion (pMCAO) to evaluate the infarct areas by 2,3,5-triphenyltetrazolium hydrochloride staining and neurological deficit...
October 16, 2017: Journal of Neuroinflammation
Simon G Comerma-Steffensen, Ingrid Carvacho, Elise R Hedegaard, Ulf Simonsen
Modulation of endothelial calcium-activated potassium (KCa) channels has been proposed as an approach to restore endothelial function. The present study investigated whether novel openers of KCa channels with small (KCa2.x) and intermediate (KCa3.1) conductance, NS309 and NS4591, improve endothelium-dependent relaxation and erectile function. Rat corpus cavernosum (CC) strips were mounted for isometric tension recording and processed for immunoblotting. Mean arterial pressure (MAP), intracavernosal pressure (ICP), and electrocardiographic (ECG) measurements were conducted in anesthetized rats...
2017: Frontiers in Pharmacology
Maj Rabjerg
Kidney cancer (Renal Cell Carcinoma (RCC)) is one of the most deadly malignancies due to frequent late diagnosis and poor treatment options. Histologically, RCC embraces a wide variety of different subtypes with the clear cell variant (ccRCC) being the most common, accounting for 75-90% of all RCCs. At present, the surveillance protocols for follow-up of RCC patients after radical nephrectomy are based on the American Joint Committee on Cancers (AJCC) pathological tumor-node-metastasis (TNM) classification system...
October 2017: Danish Medical Journal
Zhihua Yu, Yanxia Wang, Lu Qin, Hongzhuan Chen
Airway smooth muscle cells (SMC) proliferation contributes to the airways remodeling and irreversible airway obstruction during severe asthma, but the mechanisms of airway SMC proliferation are poorly understood. Intracellular Ca(2)(+) levels play an important role in regulating cell proliferation. We have previously reported KCa3.1 channels regulated human bronchial smooth muscle (HBSM) cells proliferation via the Ca(2+) influx as a consequence of membrane hyperpolarization. However, the role of potassium channels KCa3...
2017: Frontiers in Pharmacology
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