Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Over the past few years increasing evidence has suggested the nongenomic effects of thyroid hormone, such as the activation of the signal transduction pathways and the activation of nuclear factor-kappaB by the induction of oxidative stress. The present study was undertaken to investigate the effect of thyroid hormone on human polymorphonuclear leukocytes (PMNLs) which are known as important sources of reactive oxygen species in the circulation. The production of superoxide anion (O2-) and the activity of myeloperoxidase were determined in the presence and absence of several inhibitors of the signalling pathway. L-thyroxine (T4) l-3,5,3'-tri-iodothyronine (T3) and L-3,5-di-iodothyronine (T2) stimulated O2- production in PMNLs in a dose-dependent manner within a few minutes of addition to cells. Thyroid hormone-stimulated O2- production was partially inhibited by pertussis toxin, an inhibitor of GTP-binding G protein, and was completely abolished by the protein kinase C inhibitors calphostin C and Ro-32-0432, and by a calcium chelator (BAPTA; bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid). Thyroid hormone stimulated myeloperoxidase activity and induced 125I- incorporation into PMNLs. Furthermore, thyroid hormone pre-incubation enhanced O2- production for n-formyl-methionyl-leucyl- phenylalanine (FMLP) stimulation. In conclusion, novel nongenomic actions of thyroid hormone, the induction of superoxide anion production and the stimulation of myeloperoxidase activity in PMNLs were demonstrated. The induction of O2- production requires calcium and is mediated by a pertussis toxin-sensitive G protein via stimulation of protein kinase C(s). These results suggest the existence of a membrane-bound binding site for thyroid hormone in PMNLs and a physiological role for thyroid hormone in the cellular defence mechanisms by stimulating free-radical production.
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PMID:Nongenomic effect of thyroid hormone on free-radical production in human polymorphonuclear leukocytes. 1581 33

The in vivo roles of the hundreds of mammalian G protein-coupled receptors (GPCRs) are incompletely understood. To explore these roles, we generated mice expressing the S1 subunit of pertussis toxin, a known inhibitor of G(i/o) signaling, under the control of the ROSA26 locus in a Cre recombinase-dependent manner (ROSA26(PTX)). Crossing ROSA26(PTX) mice to mice expressing Cre in pancreatic beta cells produced offspring with constitutive hyperinsulinemia, increased insulin secretion in response to glucose, and resistance to diet-induced hyperglycemia. This phenotype underscored the known importance of G(i/o) and hence of GPCRs for regulating insulin secretion. Accordingly, we quantified mRNA for each of the approximately 373 nonodorant GPCRs in mouse to identify receptors highly expressed in islets and examined the role of several. We report that 3-iodothyronamine, a thyroid hormone metabolite, could negatively and positively regulate insulin secretion via the G(i)-coupled alpha(2A)-adrenergic receptor and the G(s)-coupled receptor Taar1, respectively, and protease-activated receptor-2 could negatively regulate insulin secretion and may contribute to physiological regulation of glucose metabolism. The ROSA26(PTX) system used in this study represents a new genetic tool to achieve tissue-specific signaling pathway modulation in vivo that can be applied to investigate the role of G(i/o)-coupled GPCRs in multiple cell types and processes.
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PMID:Probing cell type-specific functions of Gi in vivo identifies GPCR regulators of insulin secretion. 1799 56


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