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المؤلفون: Mark M. Mutawe, Richard W. Mitchell, Behzad Yeganeh, Min Hyung Ryu, Pawan K. Sharma, Sarah A. Maltby, Sujata Basu, Andrew J. Halayko
المصدر: British Journal of Pharmacology. 167:548-560
مصطلحات موضوعية: medicine.medical_specialty, Bronchoconstriction, Indomethacin, Caveolin 1, Prostaglandin, Mice, chemistry.chemical_compound, Internal medicine, medicine, Animals, Immunoprecipitation, Cyclooxygenase Inhibitors, Pharmacology & Pharmacy, Methacholine Chloride, Mice, Knockout, Pharmacology, Arachidonate 5-Lipoxygenase, Arachidonic Acid, biology, Muscle, Smooth, Epithelial Cells, Zileuton, Research Papers, Trachea, Endocrinology, Gene Expression Regulation, chemistry, Cyclooxygenase 2, Immunology, Arachidonate 5-lipoxygenase, Knockout mouse, cardiovascular system, biology.protein, Female, Arachidonic acid, Methacholine, Cyclooxygenase, Bronchial Hyperreactivity, medicine.symptom, medicine.drug
الوصف: Background And Purpose Acute silencing of caveolin-1 (Cav-1) modulates receptor-mediated contraction of airway smooth muscle. Moreover, COX-2- and 5-lipoxygenase (5-LO)-derived prostaglandin and leukotriene biosynthesis can influence smooth muscle reactivity. COX-2 half-life can be prolonged through association with Cav-1. We suggested that lack of Cav-1 modulated levels of COX-2 which in turn modulated tracheal contraction, when arachidonic acid signalling was disturbed by inhibition of COX-2. Experimental Approach Using tracheal rings from Cav-1 knockout (KO) and wild-type mice (B6129SF2/J), we measured isometric contractions to methacholine and used PCR, immunoblotting and immunohistology to monitor expression of relevant proteins. Key Results Tracheal rings from Cav-1 KO and wild-type mice exhibited similar responses, but the COX-2 inhibitor, indomethacin, increased responses of tracheal rings from Cav-1 KO mice to methacholine. The phospholipase A2 inhibitor, eicosatetraynoic acid, which inhibits formation of both COX-2 and 5-LO metabolites, had no effect on wild-type or Cav-1 KO tissues. Indomethacin-mediated hyperreactivity was ablated by the LTD4 receptor antagonist (montelukast) and 5-LO inhibitor (zileuton). The potentiating effect of indomethacin on Cav-1 KO responses to methacholine was blocked by epithelial denudation. Immunoprecipitation showed that COX-2 binds Cav-1 in wild-type lungs. Immunoblotting and qPCR revealed elevated levels of COX-2 and 5-LO protein, but not COX-1, in Cav-1 KO tracheas, a feature that was prevented by removal of the epithelium. Conclusion And Implications The indomethacin-induced hypercontractility observed in Cav-1 KO tracheas was linked to increased expression of COX-2 and 5-LO, which probably enhanced arachidonic acid shunting and generation of pro-contractile leukotrienes when COX-2 was inhibited. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.
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المؤلفون: Behzad Yeganeh, Saeid Ghavami, Mohammad Hashemi, Seyed Moayed Alavian, Padideh Davoodpour, Sudharsana R. Ande, Kevin M. Coombs, Marek Los
المصدر: Journal of Viral Hepatitis. 18:821-830
مصطلحات موضوعية: Hepatitis B virus, Hepatology, Hepatitis C virus, Autophagy, Hepatitis B, Biology, medicine.disease, medicine.disease_cause, Virology, Virus, Cell biology, Infectious Diseases, Viral replication, Drug development, medicine, Viral hepatitis
الوصف: Autophagy is a very tightly regulated process that is important in many cellular processes including development, differentiation, survival and homoeostasis. The importance of this process has al ...
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المؤلفون: Ryan H. Cunnington, Thomas Klonisch, Ian M.C. Dixon, Marek Los, Grant N. Pierce, Krista L. Bathe, Andrew J. Halayko, Sunil G. Rattan, Darren H. Freed, Saeid Ghavami, Jared J.L. Davies, Rakesh C. Arora, Behzad Yeganeh
المصدر: The FASEB Journal. 26
مصطلحات موضوعية: 0303 health sciences, Primary (chemistry), Autophagy, Biology, Biochemistry, Cell biology, 03 medical and health sciences, 0302 clinical medicine, Apoptosis, Genetics, Cardiac myofibroblasts, Molecular Biology, 030217 neurology & neurosurgery, 030304 developmental biology, Biotechnology
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