Calcium-sensing receptor-mediated TNF production in medullary thick ascending limb cells
| العنوان: | Calcium-sensing receptor-mediated TNF production in medullary thick ascending limb cells |
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| المؤلفون: | Dairong Wang, John C. McGiff, Huda Ismail Abdullah, Paulina L. Pedraza, Nicholas R. Ferreri |
| المصدر: | American Journal of Physiology-Renal Physiology. 283:F963-F970 |
| بيانات النشر: | American Physiological Society, 2002. |
| سنة النشر: | 2002 |
| مصطلحات موضوعية: | Male, Transcriptional Activation, medicine.medical_specialty, Medullary cavity, Physiology, chemistry.chemical_element, Receptors, Cell Surface, Calcium, Biology, Dinoprostone, Gene Expression Regulation, Enzymologic, Rats, Sprague-Dawley, Calcium Chloride, Internal medicine, medicine, Renal medulla, Extracellular, Animals, Promoter Regions, Genetic, Receptor, Cells, Cultured, Protein Kinase C, Protein kinase C, Tumor Necrosis Factor-alpha, Rats, Cell biology, Isoenzymes, Endocrinology, medicine.anatomical_structure, chemistry, Cyclooxygenase 2, Prostaglandin-Endoperoxide Synthases, Loop of Henle, Tumor necrosis factor alpha, Calcium-sensing receptor, Peptides, Receptors, Calcium-Sensing |
| الوصف: | Medullary thick ascending limb (mTAL) cells in primary culture express the Ca2+-sensing receptor (CaR), a G protein-coupled receptor that senses changes in extracellular Ca2+(Ca[Formula: see text]) concentration, resulting in increases of intracellular Ca2+concentration and PKC activity. Exposure of mTAL cells to either Ca[Formula: see text] or the CaR-selective agonist poly-l-arginine increased TNF-α synthesis. Moreover, the response to Ca[Formula: see text] was enhanced in mTAL cells transfected with a CaR overexpression vector. Transfection of mTAL cells with a TNF promoter construct revealed an increase in reporter gene activity after exposure of the cells to Ca[Formula: see text], suggesting that intracellular signaling pathways initiated by means of activation of a CaR contribute to TNF synthesis by a mechanism that involves transcription of the TNF gene. Neutralization of TNF activity with an anti-TNF antibody attenuated Ca2+-mediated increases in cyclooxygenase-2 (COX-2) protein expression and PGE2synthesis, suggesting that TNF exerts an autocrine effect in the mTAL, which contributes to COX-2-mediated PGE2production. Preincubation with the PKC inhibitor bisindolylmaleimide I inhibited Ca2+-mediated TNF production. Significant inhibition of COX-2 protein expression and PGE2synthesis also was observed when cells were challenged with Ca[Formula: see text] in the presence of bisindolylmaleimide I. The data suggest that increases in TNF production subsequent to activation of the CaR may be the basis of an important renal mechanism that regulates salt and water excretion. |
| تدمد: | 1522-1466 1931-857X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cb1e18a948e1337dc94b202c818eeb4eTest https://doi.org/10.1152/ajprenal.00108.2002Test |
| رقم الانضمام: | edsair.doi.dedup.....cb1e18a948e1337dc94b202c818eeb4e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221466 1931857X |
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