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Fei Sun, Lu Xiao, Xin-Xing Jang, Ying Xiong, Qi Li, Xiao-Jing Yue, Yun-Jian Wei, Yan-Xing Wei, Yan-Lin Ma, Yan-Hong Yu
Transient receptor potential vanilloid 6 (TRPV6) has been shown to promote caner proliferation in several solid tumors, leading to unfavorable clinical outcomes. Our study aimed to elucidate the clinical significance of TRPV6 in patients with early-stage cervical squamous cell carcinoma (CSCC). The mRNA expression of TRPV6 was measured in 12 paired early-stage CSCC specimens and six cervical carcinoma cell lines using quantitative real-time PCR (qRT-PCR). Western blotting and immunohistochemistry (IHC) were employed to examine the protein expression level of TRPV6 in four paired specimens, 175 paraffin-embedded early-stage CSCC specimens, and 50 normal cervical tissues (NCTs), respectively...
October 17, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Jae-Hwan Lee, Changhwan Ahn, Hee Young Kang, Eui-Ju Hong, Sang-Hwan Hyun, Kyung-Chul Choi, Eui-Bae Jeung
Octylphenol (OP) and bisphenol A (BPA) are known as endocrine-disrupting chemicals (EDCs). During pregnancy, the expression of steroid hormone receptors is controlled by maternal and fetal nutrition. To evaluate the impact of EDCs during pregnancy, ethinyl estradiol (EE, 0.2 mg/kg/day), OP (50 mg/kg/day), and BPA (50 mg/kg/day) were administered to pregnant mice. The mRNA levels of TRPV6 (transient receptor potential cation channels in subfamily V, member 6) decreased significantly by EE and OP. The PMCA1 (ATPase, Ca(++) transporting, plasma membrane 1) mRNA and protein levels decreased significantly by EE, OP, and BPA...
2016: International Journal of Environmental Research and Public Health
Sara Azarpeykan, Keren E Dittmer, Jonathan C Marshall, Kalyani C Perera, Erica K Gee, Els Acke, Keith G Thompson
The aim of this study was to determine the relative abundance and relationship of vitamin D responsive and calcium transporting transcripts (TRPV5, TRPV6, calD9k, calD28k, PMCA, NCX1, CYP27B1, CYP24A1, and VDR) in ovine, canine and, equine kidney using quantitative real-time PCR (RT-qPCR), and then perform a comparison between the three species. Renal tissue samples were harvested post-mortem from 10 horses, 10 sheep, and five dogs. Primers were designed for each gene. For each sample total RNA was extracted, cDNA synthesised, and RT-qPCR was performed...
2016: PloS One
Susana Cubillos, Johannes Norgauer
Psoriasis is an inflammatory skin disease with or without joint involvement. In this disease, the thickened epidermis and impaired barrier are associated with altered calcium gradients. Calcium and vitamin D are known to play important roles in keratinocyte differentiation and bone metabolism. Intracellular calcium is regulated by calcium-sensing receptor (CASR), calcium release-activated calcium modulator (ORAI) and stromal interaction molecule (STIM). Other proteins modulated by vitamin D play important roles in calcium regulation e...
October 2016: International Journal of Molecular Medicine
Marek Skrzypski, Paweł A Kołodziejski, Stefan Mergler, Noushafarin Khajavi, Krzysztof W Nowak, Mathias Z Strowski
Highly Ca(2+) permeable receptor potential channel vanilloid type 6 (TRPV6) modulates a variety of biological functions including calcium-dependent cell growth and apoptosis. So far, the role of TRPV6 in controlling growth of pancreatic neuroendocrine tumour (NET) cells is unknown. In the present study, we characterize the expression of TRPV6 in pancreatic BON-1 and QGP-1 NET cells. Furthermore, we evaluate the impact of TRPV6 on intracellular calcium, the activity of nuclear factor of activated T-cells (NFAT) and proliferation of BON-1 cells...
August 2016: Bioscience Reports
Yuan Jiang, Hui Gou, Jiang Zhu, Si Tian, Lehua Yu
It is well known that local anesthetics have a broad spectrum of pharmacological actions, acting as nerve blocks, and treating pain and cardiac arrhythmias via blocking of the sodium channel. The use of local anesthetics could reduce the possibility of cancer metastasis and recurrence following surgical tumor excision. The purpose of the present study was to investigate the inhibitory effect of lidocaine upon the invasion and migration of transient receptor potential cation channel subfamily V member 6 (TRPV6)-expressing cancer cells...
August 2016: Oncology Letters
Jinmei Xiang, Rui Guo, Chunyun Wan, Liming Wu, Shijin Yang, Dingzong Guo
Stanniocalcin-1 (STC1) is a calcium and phosphate regulatory hormone. However, the exact molecular mechanisms underlying how STC1 affects Ca(2+) uptake remain unclear. Here, the expression levels of the calcium transport proteins involved in transcellular transport in Caco2 cells were examined following over-expression or inhibition of STC1. These proteins include the transient receptor potential vanilloid members (TRPV) 5 and 6, the plasma membrane calcium ATPase 1b (PMCA1b), the sodium/calcium exchanger (NCX1), and the vitamin D receptor (VDR)...
2016: International Journal of Molecular Sciences
Kei Saotome, Appu K Singh, Maria V Yelshanskaya, Alexander I Sobolevsky
Precise regulation of calcium homeostasis is essential for many physiological functions. The Ca(2+)-selective transient receptor potential (TRP) channels TRPV5 and TRPV6 play vital roles in calcium homeostasis as Ca(2+) uptake channels in epithelial tissues. Detailed structural bases for their assembly and Ca(2+) permeation remain obscure. Here we report the crystal structure of rat TRPV6 at 3.25 Å resolution. The overall architecture of TRPV6 reveals shared and unique features compared with other TRP channels...
June 23, 2016: Nature
Phanindra Velisetty, Istvan Borbiro, Marina A Kasimova, Luyu Liu, Doreen Badheka, Vincenzo Carnevale, Tibor Rohacs
Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] is an important cofactor for ion channels. Affinity for this lipid is a major determinant of channel inhibition by depletion of PI(4,5)P2 upon phospholipase C (PLC) activation. Little is known about what determines PI(4,5)P2 affinity in mammalian ion channels. Here we report that two members of the Transient Receptor Potential Vanilloid (TRPV) ion channel family, TRPV5 and TRPV6 lack a positively charged residue in the TM4-TM5 loop that was shown to interact with PI(4,5)P2 in TRPV1, which shows high affinity for this lipid...
2016: Scientific Reports
Yan Zhang, Jin Shao, Zhi Wang, Tieyi Yang, Shuyi Liu, Yue Liu, Xinbing Fan, Weiguang Ye
The present study was performed in order to examine bone loss and calcium homeostasis in mice with glucocorticoid (GC)-induced osteoporosis (GIOP) following treatment with the aqueous extract of pomegranate seed (AE-PS). In addition, a comparative study with alendronate was performed. Biomarkers in the serum and the urine were measured. The tibias, kidney and duodenum were removed in order to measure the levels of bone calcium, protein expression as well as to perform histomorphological analysis of the bone...
August 2016: International Journal of Molecular Medicine
Julia Rosendahl, Hannah S Braun, Katharina T Schrapers, Holger Martens, Friederike Stumpff
Large quantities of protein are degraded in the fermentative parts of the gut to ammonia, which is absorbed, detoxified to urea, and excreted, leading to formation of nitrogenous compounds such as N2O that are associated with global warming. In ruminants, channel-mediated uptake of NH4 (+) from the rumen predominates. The molecular identity of these channels remains to be clarified. Ruminal cells and epithelia from cows and sheep were investigated using patch clamp, Ussing chamber, microelectrode techniques, and qPCR...
August 2016: Pflügers Archiv: European Journal of Physiology
Gladys O Latunde-Dada
Heme is of significant importance in iron nutrition and in systemic iron metabolism. The crux of the matter is that while much is known about non-heme metabolism, the vectorial import of exogenous porphyrin macromolecules into the enterocyte and possibly into blood circulation is still speculative. The inhibitory effect of calcium on heme iron absorption has been previously reported in the literature. This paper postulates that the gastrointestinal Ca transporter, TRPV6, might be a putative transporter of heme and might account for reduced heme absorption in the presence of Ca...
June 2016: Medical Hypotheses
Tatiana Claro da Silva, Christian Hiller, Zhibo Gai, Gerd A Kullak-Ublick
Vitamin D3 regulates genes critical for human health and its deficiency is associated with an increased risk for osteoporosis, cancer, diabetes, multiple sclerosis, hypertension, inflammatory and immunological diseases. To study the impact of vitamin D3 on genes relevant for the transport and metabolism of nutrients and drugs, we employed next-generation sequencing (NGS) and analyzed global gene expression of the human-derived Caco-2 cell line treated with 500nM vitamin D3. Genes involved in neuropeptide signaling, inflammation, cell adhesion and morphogenesis were differentially expressed...
October 2016: Journal of Steroid Biochemistry and Molecular Biology
Ellen P M van Loon, Robert Little, Sukhpal Prehar, René J M Bindels, Elizabeth J Cartwright, Joost G J Hoenderop
Calcium (Ca2+) is vital for multiple processes in the body, and maintenance of the electrolyte concentration is required for everyday physiological function. In the kidney, and more specifically, in the late distal convoluted tubule and connecting tubule, the fine-tuning of Ca2+ reabsorption from the pro-urine takes place. Here, Ca2+ enters the epithelial cell via the transient receptor potential vanilloid receptor type 5 (TRPV5) channel, diffuses to the basolateral side bound to calbindin-D28k and is extruded to the blood compartment via the Na+/Ca2+ exchanger 1 (NCX1) and the plasma membrane Ca2+ ATPase (PMCA)...
2016: PloS One
Zongtao Lin, Srinivasa R Marepally, Tae-Kang Kim, Zorica Janjetovic, Allen Sw Oak, Arnold E Postlethwaite, Linda K Myers, Robert C Tuckey, Andrzej T Slominski, Duane D Miller, Wei Li
Vitamin D3 (D3) can be metabolized by cytochrome P450scc (CYP11A1) into 20S-hydroxyvitamin D3 (20D3) as a major metabolite. This bioactive metabolite has shown strong antiproliferative, antifibrotic, pro-differentiation and anti-inflammatory effects while being non-toxic (non-calcemic) at high concentrations. Since D3 analogs with two symmetric side chains (Gemini analogs) result in potent activation of the vitamin D receptor (VDR), we hypothesized that the chain length and composition of these types of analogs also containing a 20-hydroxyl group would affect their biological activities...
March 2016: Anticancer Research
Shui-Shen Zhang, Xuan Xie, Jing Wen, Kong-Jia Luo, Qian-Wen Liu, Hong Yang, Yi Hu, Jian-Hua Fu
BACKGROUND: TRPV6 is over-expressed and promotes the proliferation and invasion in many cancers. The association between the expression of TRPV6 and clinical outcome in esophageal squamous cell carcinoma (ESCC) has not been studied yet. We aim to elucidate the role of TRPV6 in predicting prognosis of patients with ESCC. METHODS: In the retrospective study, mRNA level of TRPV6 was examined in patients (N = 174) from Sun Yat-sen University Cancer Center (mRNA cohort) and protein level of TRPV6 was examined in patients (N = 218) from Linzhou Cancer Hospital (protein cohort)...
2016: Diagnostic Pathology
Kannikar Wongdee, Jarinthorn Teerapornpuntakit, Chanakarn Sripong, Asma Longkunan, Wasutorn Chankamngoen, Chutiya Keadsai, Kamonshanok Kraidith, Nateetip Krishnamra, Narattaphol Charoenphandhu
As the principal lactogenic hormone, prolactin (PRL) not only induces lactogenesis but also enhances intestinal calcium absorption to supply calcium for milk production. How the intestinal epithelium res-ponses to PRL is poorly understood, but it is hypothesized to increase mucosal absorptive surface area and calcium transporter expression. Herein, lactating rats were found to have greater duodenal, jejunal and ileal villous heights as well as cecal crypt depths than age-matched nulliparous rats. Morphometric analyses in the duodenum and cecum showed that their mucosal adaptations were diminished by bromocriptine, an inhibitor of pituitary PRL release...
January 15, 2016: Archives of Biochemistry and Biophysics
Chien-Te Lee, Hwee-Yeong Ng, Yueh-Ting Lee, Li-Wen Lai, Yeong-Hau H Lien
Calbindin-D28k (CBD-28k) is a calcium binding protein located in the distal convoluted tubule (DCT) and plays an important role in active calcium transport in the kidney. Loop and thiazide diuretics affect renal Ca and Mg handling: both cause Mg wasting, but have opposite effects on Ca excretion as loop diuretics increase, but thiazides decrease, Ca excretion. To understand the role of CBD-28k in renal Ca and Mg handling in response to diuretics treatment, we investigated renal Ca and Mg excretion and gene expression of DCT Ca and Mg transport molecules in wild-type (WT) and CBD-28k knockout (KO) mice...
February 1, 2016: American Journal of Physiology. Renal Physiology
Bernd Schröder, Mirja R Wilkens, Gundula E Ricken, Sabine Leonhard-Marek, David R Fraser, Gerhard Breves
The quantitative role of different segments of the gastrointestinal tract for Ca absorption, the respective mechanisms, and their regulation are not fully identified for ruminants, that is, cattle. In different in vitro experiments the forestomach wall has been demonstrated to be a major site for active Ca absorption in sheep and goats. In order to further clarify the role of the bovine rumen for Ca transport with special attention to luminal Ca concentrations, its ionic form, and pH, electrophysiological and unidirectional flux rate measurements were performed with isolated bovine rumen epithelial tissues...
November 2015: Physiological Reports
Céline Simonin, Mahendra Awale, Michael Brand, Ruud van Deursen, Julian Schwartz, Michael Fine, Gergely Kovacs, Pascal Häfliger, Gergely Gyimesi, Abilashan Sithampari, Roch-Philippe Charles, Matthias A Hediger, Jean-Louis Reymond
Herein, we report the discovery of the first potent and selective inhibitor of TRPV6, a calcium channel overexpressed in breast and prostate cancer, and its use to test the effect of blocking TRPV6-mediated Ca(2+)-influx on cell growth. The inhibitor was discovered through a computational method, xLOS, a 3D-shape and pharmacophore similarity algorithm, a type of ligand-based virtual screening (LBVS) method described briefly here. Starting with a single weakly active seed molecule, two successive rounds of LBVS followed by optimization by chemical synthesis led to a selective molecule with 0...
December 1, 2015: Angewandte Chemie
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