Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor necrosis factor alpha (TNF alpha) and parathyroid hormone-related protein (PTHrP) are both factors that have been implicated in the mechanism of hypercalcemia of malignancy. In this study we investigated the effect of TNF alpha on the PTHrP-stimulated accumulation of intracellular cyclic AMP in osteoblast-like cells. In the clonal cell line Saos-2 and in primary cell cultures from fetal rat calvaria, PTHrP-stimulated accumulation of cAMP was time- and dose-dependently inhibited by exposure to TNF alpha. Significant inhibition occurred at concentrations as low as 2 x 10(-12) M and was maximal at 1 x 10(-9) M. Inhibition was observed after 6 h and was maximal after 18 h. Inhibition by TNF alpha was probably mediated by protein kinase C, since the phorbol ester PMA mimicked the effect of TNF alpha, and the protein kinase C inhibitor H-7 completely abolished the effect of TNF alpha. In conclusion, these observations suggest a possible mechanism by which TNF alpha may modulate the effect of PTHrP on osteoblast function in the syndrome of humoral hypercalcemia of malignancy.
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PMID:Tumor necrosis factor alpha inhibits the stimulatory effect of the parathyroid hormone-related protein on cyclic AMP formation in osteoblast-like cells via protein kinase C+. 131 16

Radioisotopes have been widely used in both in vitro and in vivo studies of endocrine organs. In this lecture, results of our recent in vitro studies on calcium regulating hormones, thyroid-stimulating hormone, and gastro-intestinal hormones are reviewed. 1) Clinical evaluation of measurement of calcium regulating hormones such as PTH, calcitonin and vitamin D metabolites was demonstrated. Furthermore, problems of those assays were also discussed. Especially, simpler methods which measure intact PTH or vitamin D metabolites are to be developed. PTH-like factor, which should play the major role in hypercalcemia of malignancy, was assayed biologically. After determination of amino-acid sequence of this protein, clinical measurement should reveal mechanism of hypercalcemia of malignancy. 2) Studies on TSH-receptor antibodies by using radioreceptor assay. TSH-binding inhibitor immunoglobulins (TBII) were detected not only in 93% of untreated patients with Graves' disease, but also in 21% of patients with primary myxedema. In contrast to the thyroid-stimulating nature of TBII in Graves' patients, TBII in hypothyroid patients were disclosed to be blocking in their nature. Clinical and laboratory findings supported pathogenetic role of the blocking antibodies in the latter condition. 3) Mutual regulation between CCK and muscarinic receptors on dispersed pancreatic acini. CCK and carbachol in their higher concentrations regulated muscarinic receptor and CCK receptor, respectively. The mode of regulation of both receptors was disappearance of their high affinity binding site. TPA, an activator of protein kinase C, modulated both receptors in the same manner as CCK or carbachol. These effects of CCK and carbachol on receptors were well compatible to the restriction of carbachol or CCK induced amylase secretion by CCK or carbachol. These in vitro studies, in association with the results of in vivo studies, contribute to the developments of nuclear endocrinology.
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PMID:[The role of nuclear medicine in endocrinology]. 345 May 42