PubMed Health⌕ Search

Biomedical subjects

Y Friedman

Publications and source records attributed to Y Friedman.

At least 55 records · Page 3Linked to original sources
PubMed1985

Diacylglycerol-activated, calcium/phospholipid-dependent protein kinase (protein kinase C) activity in bovine thyroid.

Bovine thyroid 100,000 X g supernatant contained diacylglycerol-activated, calcium/phospholipid-dependent protein kinase (protein kinase C). The protein kinase C was partially purified using ion-exchange chromatography and characterized. Substrate specificity studies revealed that the enzyme was most active when histone F1 was used as substrate. The thyroid protein kinase C was not stimulated by Ca2+ or phosphatidylserine (PS), but was stimulated by the combination of the two by 570%. Diolein stimulated the kinase by increasing its sensitivity to Ca2+. Other phospholipids could not substitute for PS and were ineffective in stimulating the protein kinase C in the absence of diolein. However, in the presence of diolein some of the other phospholipids were stimulatory albeit not to the extent of PS. Quercitin, a protein kinase C inhibitor in other systems, inhibited the thyroid enzyme in a dose-related manner. Protein kinase C could also be demonstrated using endogenous thyroid proteins as substrate. Separation of these 32P-labelled proteins by electrophoresis and subsequent autoradiography revealed that three proteins were phosphorylated by the protein kinase C of approximate molecular weights 60,000, 45,000, and less than 29,000. These results offer a possible mechanism by which Ca2+ and/or diacylglycerol effects may be mediated in thyroid.

Animals↗
PubMed1985

Forskolin and 12-0-tetradecanoylphorbol-13-acetate mimic thyrotropin-stimulated protein iodination in mouse thyroid.

In the present study, the capacity of the diterpene, forskolin, and the phorbol ester, 12-0-tetradecanoylphorbol-13-acetate (TPA), to stimulate protein iodination in freshly dispersed mouse thyroid open follicles was assessed. Although both agents stimulated 125I incorporation into TCA precipitable material, dose response curves (0.1 - 25 microM) showed that maximal concentrations of either agonist alone failed to reproduce the stimulatory effect of a maximal concentration of thyrotropin (TSH; 50 mU/ml). When a maximal concentration of forskolin (20 microM) and TPA (10 microM) were added in combination, the stimulatory effect was additive and mimicked the effect of TSH. TPA had no significant effect on either basal or forskolin-stimulated cyclic-AMP production. We conclude that the regulation of protein iodination by TSH may involve both the adenylate cyclase-cyclic-AMP-dependent protein kinase system and the diacylglycerol-activated calcium/phospholipid-dependent protein kinase C pathway.

Adenylyl Cyclases↗
PubMed1985

Differential effects of polyamines on rat thyroid protein kinase activities.

Ornithine decarboxylase, the rate-limiting enzyme in polyamine biosynthesis, has been shown to be regulated in thyroid by thyrotropin both in vivo and in vitro. Little, however, is known of the role of polyamines in thyroid cell function. Since studies in other tissues suggest that polyamines may influence protein phosphorylation, we studied the effect of the polyamines on various protein kinase activities in rat thyroid. Putrescine, spermidine, and spermine inhibit cyclic-AMP-dependent histone H1 kinase activity when measured in the cytosol fraction of rat thyroid; this effect is largely reproduced by NaCl concentrations of equivalent ionic strength. Both spermidine and spermine effect a 1.6-2.4-fold increase in cytosolic cyclic-AMP-independent (messenger-independent) casein kinase activity; stimulation by both polyamines is maximal at 5mM. A similar profile of stimulation is observed for messenger-independent casein kinase activity in crude nuclear preparations. Sodium chloride fails to stimulate both cytosolic and nuclear messenger-independent casein kinase activities at ionic strength equivalent to the spermine concentrations used. Spermine, but not putrescine, spermidine, or sodium chloride, inhibits calcium/phospholipid-dependent protein kinase C activity in cytosol extracts partially purified by DEAE chromatography. These findings suggest that regulation of protein kinase(s) by polyamines may represent a proximal locus (i) of action of thyrotropin-regulated ornithine decarboxylase activity in thyroid.

Animals↗
PubMed1983

Effects of proteolytic enzymes and protease inhibitors on bovine thyroid adenylate cyclase activity.

Trypsin, chymotrypsin, and papain stimulate basal adenylate cyclase activity in bovine thyroid plasma membranes in a dose-related, albeit biphasic, fashion. Each of the proteases enhanced TSH-stimulated adenylate cyclase activity over basal activity. The proteases also enhanced GTP-, guanosine 5'-(beta, gamma-imidotriphosphate)-, prostaglandin E1-, and cholera toxin-stimulated adenylate cyclase to varying degrees. Fluoride-stimulated activity was enhanced by chymotrypsin and papain, but not by trypsin. When Mn++ was substituted for Mg++ in the adenylate cyclase assay, no stimulation by the proteases were observed. To see if endogenous membrane proteases are required for optimal thyroid adenylate cyclase response to TSH and other stimulators, studies were performed using the protease inhibitors tosylamide 2-phenylethyl-chloromethyl ketone (TPCK) and p-tosyl-L-arginine methyl ester (TAME), inhibitors of chymotrypsin and trypsin, respectively. TPCK (0.15 mM) had no effect on basal adenylate cyclase activity, but did inhibit TSH-, trypsin-, and chymotrypsin-stimulated activities by approximately 90%. Guanosine 5'-(beta, gamma-imido) triphosphate- as well as cholera toxin-stimulated activities were inhibited by approximately 50%, whereas prostaglandin E1- and fluoride-stimulated activities were inhibited by approximately 25%. TAME (6 mM) produced similar results, except that no effect on fluoride activity was seen, while basal activity was inhibited by approximately 20%. Thus, various serine proteases augment both basal and hormone-stimulated adenylate cyclase in bovine thyroid. Since both trypsin- and chymotrypsin-stimulated as well as TSH-induced enzyme activities were inhibited by TPCK and TAME, it would appear that augmentation of thyroid adenylate cyclase activity may, in part, result from stimulation of endogenous proteases.

Adenylyl Cyclases↗
PubMed1981

Role of guanine nucleotides in the stimulation of thyroid adenylate cyclase by prostaglandin E1 and cholera toxin.

Cholera toxin in the presence of GTP increased adenylate cyclase activity in a purified bovine thyroid plasma membrane preparation, whereas, in the presence of guanosine 5'-(beta, gamma-imido)-triphosphate (Gpp(NH)P), cholera toxin had no stimulatory effect. Similarly, prostaglandin E1 enhanced the adenylate cyclase activity induced by GTP but not by Gpp(NH)p. Gpp(NH)p-stimulated adenylate cyclase activity, assayed with hydrolysis-resistant adenosine 5'-(beta, gamma-imido)-[32P]triphosphate as substrate and no ATP-regenerating system was inhibited by GDP in a competitive fashion. Furthermore, prostaglandin E1, but not cholera toxin, influenced the GDP inhibition of Gpp(NH)p-stimulated activity by increasing the concentration of GDP resulting in 50% inhibition approx. 2-fold. Inosyl nucleotides mimicked the effects of guanyl nucleotides on thyroid adenylate cyclase in that ITP could substitute for GTP in enhancing cholera toxin- and prostaglandin #1-induced activities and that inosine 5'(beta, gamma-imido)-triphosphate [Ipp(NH)p] was also a potent stimulator per se. Conclusions. (1) Cholera Toxin and prostaglandin E1 enhance thyroid adenylate cyclase activation by GTP (or ITP), but have no stimulatory effect on the Gpp(NH)p (or Ipp(NH)p) response; (2) the stimulatory effect of prostaglandin E1 on adenylate cyclase may result from decreased affinity for GDP at the guanine nucleotide regulatory site; (3) the date regarding cholera toxin stimulation of thyroid adenylate cyclase are consistent with the hypothesis that cholera toxin exerts its effect by inhibiting an endogenous GTPase.

Adenylyl Cyclases↗
PubMed1981

Arachidonate metabolism in the mouse thyroid implication of the lipoxygenase pathway in thyrotropin action.

The present study of compares the effects of various inhibitors of arachidonate metabolism on mouse thyroid cyclo-oxygenase and lipoxygenase activities and thyrotropin-augmented cyclic-AMP accumulation. Mouse thyroid homogenate converts [1-14C]- arachidonate to several products of the cyclo-oxygenase pathway as well as one major product of the lipoxygenase pathway, 12-L-hydroxyeicosatetraenoic acid (12-Hete). Prostaglandin (PG) formation in thyroid homogenates is inhibited by 1-10 microM indomethacin and etya. 12-HETE accumulation is reduced by 91%, 83% and 20% by 5 microM ETYA, 15-HETE, and indomethacin, respectively. Thyrotropin-stimulated cyclic-AMP accumulation, measured in whole thyroid lobes by radioimmunoassay, is reduced by 45% and 73% by 50 microM and 100 microM ETYA, respectively; indomethacin is without effect at these concentrations. 15-HETE reduces thyrotropin-augmented cyclic-AMP accumulation by 57% and 100 microM. In product inhibition studies, 10 microM 12-HETE reduced the formation of radiolabeled 12-HETE by 20%. 10 microM PGE2, PGF2 alpha or PGD2 had no effect on [1-14C]-PG formation. 12-HETE, however, reduced PG synthesis by 76% at 10 microM. This is the first report implicating the arachidonate lipoxygenase pathway in thyrotropin action at the level of cyclic-AMP regulation. Additionally, our finding that 12-HETE inhibits prostaglandin synthesis suggests that the cyclo-oxygenase and lipoxygenase pathways in the mouse thyroid may be highly integrated.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1980

Peripheral fiber correlates to noxious thermal stimulation in humans.

Minimal conduction velocities of peripheral nerves contributing to acute thermal pain sensation in human volunteer subjects were calculated. Purely thermal stimulation was administered by a low power laser beam directed at the subjects' fingers, and subjective pain responses correlated with a peak in the event-related brain potential (ERBP). These cerebral responses were found to preclude C fiber peripheral activity from this phenomenon.

Cerebral Cortex↗
PubMed1980

Somatosensory evoked potentials and noxious stimulation in patients with intractable, noncancer pain syndromes.

Investigations of the evoked potentials (EPs) to noxious laser stimulation have indicated consistent strong linear relationships between subjective response (R), stimulus intensity (S), and EP amplitude (A). Thirty patients with chronic intractable benign pain syndromes (CIBPS) were tested to determine whether their patterns differed from previous studies with normal volunteers. Nearly half of the CIBPS patients were found to be relatively insensitive to acute pain stimuli. A large number were also found to show negative relationships between S and A. These differences from control subjects were considered of potential importance in their implications concerning the nature of chronic pain and its differences from the acute pain process.

Adult↗
PubMed1980

Single trial analysis of evoked potentials to noxious thermal stimulation in man.

Thermal (laser) evoked responses were obtained from 13 male volunteers. A single trial analysis technique with a latency adjusting adaptive filter was used to analyze evoked response amplitudes. Significant and substantial within-subject linear correlations were found between the magnitude (A) of the primary waveform (RMS muV of the P200--N300-P400 complex ) and subjective pain response (R) as well as stimulus intensity (S). Since subjective pain response was strongly correlated with stimulus intensity, the partial correlation coefficients were calculated for R vs. A with S controlled, and S vs. A with R controlled, for each subject. The partial correlations revealed a much stronger relationship between subjective response and the evoked response amplitude, suggesting that the primary complex may measure neural events in the pain perception process rather than transduction and transmission of the stimulus event.

Computers↗
PubMed1980

Chronic regulation of rat thyroid prostaglandin synthetase activity by endogenous thyrotropin.

Prostaglandin (PG) synthetase activity was measured in the rat thyroid after hypophysectomy, T4, and methylthiouracil treatment in order to explore the possibility that PG synthetase is subject to chronic control by endogenous TSH. T4 treatment (5 mg/liter drinking water) lowered PG synthetase activity, as measured in whole homogenates, by 22% and 31% after 2 and 4 days, respectively. Similarly, PG synthetase activity was reduced by 16% and 42% 2 and 4 days after hypophysectomy. Methylthiouracil treatment (100 mg/liter drinking water) effected 51% and 78% increases in synthetase activity by days 2 and 4, respectively. Additionally, differential effects with regards to PGE2 to PGF 2 alpha ratios were observed. The limited prostaglandin-catabolizing capacity of the rat thyroid warrants the conclusion that the observed TSH effects are expressed at the level of the PG synthetase complex.

15-Oxoprostaglandin 13-Reductase↗
PubMed1979

Effects of cholera toxin on thyroid cyclic AMP-dependent protein kinase and ornithine decarboxylase activities.

Cholera toxin activated beef thyroid cyclic AMP-dependent protein kinase in a dose (0.2 to 8 microgram/ml)-related fashion. Thus, when beef thyroid slices were incubated with toxin (8 microgram/ml) for 90 minutes and then assayed for protein kinase, the activity ratio (i.e. -cyclic AMP/+cyclic AMP) increased from 0.32 +/- 0.02 to 0.77 +/- 0.06. The toxin (5 microgram/ml)-induced increase was abolished by inclusion of ganglioside GM1 in the incubation medium (I50, 0.7 microgram/ml), whereas, gangliosides GD1a and GT1 were without effect. In contrast, TSH-activated protein kinase was unaffected by ganglioside addition. Cholera toxin increased rat thyroid ornithine decarboxylase (ODC) activity in-vitro in a dose (0.1 to 10 microgram/ml)-related fashion [basal, 100 cf cholera toxin (10 microgram/ml), 1500 pmol 14CO2/g tissue/30 min]. The toxin (1 microgram/ml)- (but not TSH-) induced increase in ODC was abolished by inclusion of ganglioside Ga and GT1 were without effect. Cholera toxin stimulation of ODC was inhibited by indomethacin or iodide as are the stimulatory effects of TSH or dibutyryl cyclic AMP. These results demonstrate that although there are differences in the TSH and cholera toxin responses with respect to receptor (ganglioside) interaction, they nevertheless elicit similar intracellular responses in thyroid.

Animals↗