Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin stimulated phosphorylation of tyrosine residues by the insulin receptor kinase may be part of a signalling mechanism associated with insulin's action. We report that indomethacin inhibited the phosphorylation of the beta-subunit of the solubilized adipocyte insulin receptor. Indomethacin also inhibited several insulin-sensitive processes in intact rat adipocytes. Indomethacin (1 mM) inhibited basal phosphorylation of the beta-subunit of the solubilized insulin receptor by 60% and insulin-stimulated phosphorylation by 30%. In adipocytes, indomethacin inhibited basal 3-0-[methyl-14C]-methyl-D glucose transport by 50% (P less than 0.01), D-[6-14C]-glucose oxidation by 50% (P less than 0.01), D-[6-14C]-glucose conversion to lipid by 30% (P less than 0.01), and D-[1-14C]-glucose conversion to lipid by 60% (P less than 0.01). Similarly, indomethacin inhibited insulin-stimulated 3-0-[methyl-14C]-methyl-D-glucose transport by 75% (P less than 0.01), D-[6-14C]-glucose oxidation by 20% (P less than 0.05), D-[1-14C]-glucose oxidation by 35% (P less than 0.01), D-[6-14C] glucose conversion to lipid by 25% (P less than 0.01), and D-[1-14C] glucose conversion to lipid by 45% (P less than 0.01). In contrast, insulin binding to its receptor, basal D-[1-14C]-glucose oxidation and both basal and insulin-stimulated activation of glycogen synthase were unaffected by indomethacin. Thus, indomethacin partially inhibited autophosphorylation of the solubilized insulin receptor on tyrosine and partially inhibited some but not all of insulin's actions.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Biochem 1985 Nov
PMID:Inhibition of insulin receptor phosphorylation by indomethacin. 393 10

In the rat, injection of Freund's complete adjuvant was accompanied by a significant increase in concanavalin A (Con A)-reactivity of selected plasma proteins along with an increase in concentrations of selected proteins known as acute phase proteins. We have evaluated the effect of bindarit, (2-[(1-benzyl-indazol-3-yl)methoxy]-2-methyl propionic acid), on the expression of alpha 2-macroglobulin, a known acute-phase protein in the rat. This compound has previously been shown to inhibit heat-induced denaturation of rat serum albumin and to strongly reduce the secondary phase response of adjuvant induced arthritis. Adult rats were induced with chronic inflammation by injection with Freund's complete adjuvant. Bindarit was administered to the chronic inflamed rats as a 0.5% medicated diet. Indomethacin, given by gavage daily at a dose of 1 mg/kg body weight, was used as a reference drug. Qualitative and quantitative changes of Con A-reactive proteins and alpha 2-macroglobulin were examined by lectin- and immuno-blots, and by radioimmunoassay. It was noted that the concentration of alpha 2-macroglobulin increased in rats with adjuvant induced arthritis. The addition of bindarit and indomethacin were able to reduce the concentration of alpha 2-macroglobulin as well as the Con A-reactivity of various proteins to normal level 37 days following treatment. We have also examined the effects of chronic inflammation on the levels of rat clusterin, a testicular and serum glycoprotein related to programmed cell death, tissue regression, and complement cascade reaction; and testibumin, a testicular FSH and testosterone-responsive protein with unknown function. It was noted that chronic inflammation did not induce significant changes in both the clusterin and testibumin concentrations in these experimental groups. The involvement of protein glycosylation and denaturation in the production of new antigenic determinants, their role in the development of chronic inflammatory disease and the potential use of bindarit to investigate the relationship between abnormal glycosylation and autoimmune disease were discussed.
Biochem Mol Biol Int 1993 Mar
PMID:Chronic inflammatory response in the rat can be blocked by bindarit. 768 47

AS101 as a new immunomodulator has been shown to induce production of a variety of cytokines such as interleukin-1, interleukin-2, colony-stimulating factor, interferon-gamma and tumor necrosis factor, and demonstrate a potential chemo-protection from chemotherapy induced immunosuppression and hematopoietic toxicity in tumor bearing mice and cancer patients on phase I and II clinical trials. This study was designed to verify whether AS101 exerts a cytoprotective effect in rats and mice with gastric lesions induced by intragastric (i.g.) instilling of 0.6N hydrochloride (HCl). AS101 given intraperitoniously (i.p) 2h before a HCl administration markedly prevented HCl-induced gastric lesions both in rats and mice. It also accelerated the ulcer repair when given i.p. 1h after a HCl treatment. Indomethacin (IND), a cyclo-oxygenase inhibitor, given i.p. at a non-ulcerogenic dose of 5mg/kg 1h before AS101 administration, abolished its protective effect. Mechanistic analysis showed that the gastric cytoprotective property of AS101 appears to be mediated through the induction of prostaglandin E2 (PGE2) and epidermal growth factor (EGF), of which, both prevent the gastric mucosa from HCl ulceration while EGF also contributes to the promotion of ulcer repair. This study adds another cytoprotective property to the known immunomodulating role of AS101.
Res Commun Mol Pathol Pharmacol 1995 Jan
PMID:The cytoprotective effect of the immunomodulator AS101 against hydrochloride induced gastric lesions. 773 28

The ability of indomethacin to scavenge hydroxyl radical (.OH) using high pressure liquid chromatography (HPLC) was investigated. .OH radical was generated by photolysis of H2O2 (1.5-10 mmoles/L) with UV light and was trapped with salicyclic acid (500 nmoles). H2O2 produced .OH in a concentration-dependent manner as estimated by .OH adduct products 2,3- and 2,5-dihydroxybenzoic acid (DHBA). Indomethacin in increasing concentrations (5-600 mumoles/L) produced increasing inhibition of generation of 2,3-DHBA (7-67%) and of 2,5-DHBA (7-77%). The results indicate that indomethacin scavenges .OH in a concentration-dependent manner.
Mol Cell Biochem 1994 Jul 27
PMID:Hydroxyl radical-scavenging property of indomethacin. 784 67

We investigated the effects of cultured epithelial cells and supernatants on resting membrane potential and excitatory neuroeffector transmission in smooth muscle cells of dog trachea and bronchioles. The mean resting membrane potential of the mucosa-free tracheal smooth muscle cells was -59.5 +/- 1.5 mV (+/- SD). Application of cultured epithelial cells (> 2.5 x 10(5) cells/ml) hyperpolarized the membrane, resulting in a potential of -64.5 +/- 1.7 mV. The supernatant of the cultured epithelial cells also increased the resting membrane potential of the mucosa-free tracheal smooth muscle cells by 4 to 9 mV. These hyperpolarizing actions were not modified by indomethacin (10(-5) M), l-NG-nitroarginine (10(-5) M), or oxyhemoglobin (10(-5) M), but were inhibited by glibenclamide (10(-6) M). The supernatants of the cultured epithelial cells completely or partially suppressed the contractile response of epithelium-denuded bronchioles to electrical field stimulations and suppressed the amplitude of excitatory junction potentials of the trachealis evoked by electrical field stimulations. Indomethacin prevented the inhibitory effect of supernatants on the amplitude of twitch contractions and excitatory junction potentials and markedly suppressed supernatant-associated inhibition of the excitatory neuroeffector transmission. Furthermore, indomethacin with AA861, a lipoxygenase inhibitor, completely suppressed this effect. Our findings suggest that cultured airway epithelial cells spontaneously release at least two factors. One factor selectively modulates the resting membrane potential, and the other inhibits the excitatory neuroeffector transmission.
Am J Respir Cell Mol Biol 1994 Mar
PMID:Effects of epithelial cell supernatant on membrane potential and contraction of dog airway smooth muscles. 811 50

Exposure of isolated canine tracheal epithelium to acetylcholine (Ach) increased transepithelial conductance (GT) and short-circuit current (ISC). Qualitatively different responses were obtained when the epithelium was studied as a part of an intact posterior tracheal membrane that contained smooth muscle. Ach decreased GT, did not affect ISC, and induced a 2-fold increase in measured tension. In these tissues, baseline GT was enhanced compared with that of isolated epithelium. Indomethacin inhibited the Ach-induced responses of isolated epithelium but did not alter the responses of intact airway tissue. The epithelial origin of these electrophysiologic responses was confirmed in experiments that showed that denudation of intact tracheal tissue greatly increased base-line GT, eliminated ISC, abolished the electrophysiologic response to Ach, and enhanced Ach-induced smooth muscle constriction. The qualitatively different responses to Ach of intact tracheal membrane and epithelium alone suggest that the behavior of airway epithelia in the whole animal may be significantly different from that observed in conventional in vitro studies of isolated epithelia.
Am J Respir Cell Mol Biol 1993 Apr
PMID:Submucosal tissues modulate the bioelectric properties of airway epithelium. 847 36

The objective of this study was to examine the effect of interleukin-1 beta (IL-1) on progesterone (P) biosynthesis and the potential intermediary involvement of prostaglandin (PG) E and nitric oxide (NO) in P accumulation in PMSG/hCG-primed rat corpora luteal (CL) cell cultures. Exposure of primed CL cells to IL-1 (10 ng/ml) for 48 h resulted in a 65-86% reduction (P < 0.01) in P accumulation concurrent with a 2-3.4-fold increase in PGE content, a 70% increase in PGF2 alpha content and a 1.9-3.3-fold increase in nitrite generation. These effects were abolished by the IL-1 receptor antagonist, suggesting specific IL-1 receptor-mediated effects. Indomethacin, a cyclooxygenase inhibitor, abolished PGE and PGF2 alpha production and attenuated the basal (but not IL-1-stimulated) accumulation of P. N(G)-Nitro-L-arginine (NNLA), a competitive inhibitor of nitrite synthesis, slightly reduced basal P accumulation but had no effect on IL-1-induced suppression of P accumulation. NNLA reduced basal PGE accumulation and IL-1-stimulated PGE accumulation (55 and 61%, respectively). Transforming growth factor beta 1 (TGF-beta 1; 10 ng/ml) significantly attenuated the IL-1-stimulated PGE and NO production (61 and 42%, respectively), but did not affect the ability of IL-1 to suppress P accumulation. Thus, NO, PGF2 alpha and PGE are not obligatory intermediaries of IL-1-mediated suppression of P accumulation in rat CL, but are involved in basal P biosynthesis and NO seems to have a regulatory role in the biosynthesis of PGE. The present observations suggest a pleiotropic response of PMSG/hCG-primed CL cells to IL-1, characterized by an independent suppression of P accumulation and a concomitant increase in NO, PGF2 alpha and PGE generation. Since IL-1 attenuates P accumulation, these findings may imply a direct autocrine/paracrine function for IL-1 in the maintenance or the demise of rat CL.
Mol Cell Endocrinol 1997 Sep 30
PMID:Interleukin-1 beta inhibits progesterone accumulation in rat corpora luteal cell cultures in a mechanism dissociated from its effects on nitric oxide and prostaglandin E accumulation. 935 71

Effect of basic fibroblast growth factor (bFGF) on the expression of receptors for luteinizing hormone (LH), a marker of differentiation, was studied using estrogen-primed rat ovarian granulosa cells in primary culture. bFGF had no effect by itself but dose-dependently induced expression of functional LH receptors in the presence of insulin-like growth factor-I (IGF-I). The effect of a combination of bFGF and IGF-I was delayed in onset and the magnitude of the response was smaller when compared to the action of follicle-stimulating hormone (FSH). Scatchard analysis revealed that dissociation constant (Kd) and number of LH receptors induced by bFGF and IGF-I were 0.47 nM and 6.48 fmol/10(6) cells, respectively. Unlike FSH, bFGF plus IGF-I did not cause an immediate increase in cAMP release, however, considerable amount of cAMP release was observed in cells incubated for 72 h with bFGF plus IGF-I. Indomethacin, an inhibitor of cyclooxygenase, attenuated both LH receptor expression and cAMP release induced by bFGF plus IGF-I but had little effect on the action of FSH. Finally, a combination of bFGF and IGF-I increased production of prostaglandin E2 in granulosa cells. These results indicate that bFGF is capable of inducing LH receptor in the presence of IGF-I by a mechanism involving production of prostaglandin E2.
Mol Cell Endocrinol 1994 May
PMID:Basic fibroblast growth factor induces luteinizing hormone receptor expression in the presence of insulin-like growth factor-I in ovarian granulosa cells. 939 41

Endometrial stromal cells from rat uteri differentially sensitized for the decidual cell reaction in vivo and which undergo differing degrees of decidualization in vitro were cultured and plasminogen activator (PA) in the medium determined. The cells were obtained by enzymatic dispersion from the uteri of ovariectomized, steroid-treated rats at the equivalent of day 4, 5, or 6 of pseudopregnancy or on day 5 from rats treated on day 4 with 0, 0.3, or 1.0 microgram estradiol (low, intermediate, or high dose of estradiol, respectively) and cultured for 24, 48, or 72 hr. For cells from day 4, 5, and 6 uteri cultured under control conditions, PA activity in the medium was greatest for day 5 cells, which were from uteri maximally sensitized for decidualization both in vivo and in vitro. By contrast, for cells from low-, intermediate-, and high-estradiol uteri, PA activity in the medium was greatest for the high-estradiol cells; these cells do not undergo decidualization in vivo or in vitro to the same extent as intermediate-estradiol cells. Indomethacin, an inhibitor of prostaglandin (PG) synthesis, reduced PGE2 accumulation to nondetectable amounts and for most cultures decreased PA activity in the medium, suggesting that endogenous PG production regulated in part PA secretion under control conditions. The addition of PGE2 with indomethacin increased PA activities above those under control conditions, but activities were still lower for day 4 and 6 cells compared with day 5 cells, and for low- and intermediate-estradiol cells compared with high-estradiol cells. This indicates that the differences in PA secretion are not explainable by differences in PGE2 production. Northern blot analysis of RNA from cells cultured for 72 hr under control conditions did not reveal significant differences in steady-state concentrations of mRNA for urokinase-type PA or plasminogen activator inhibitor 1, but those for tissue-type PA were lower in day 6 cells compared with day 4 and 5 cells. It is concluded that PA activity secreted by the cultured endometrial stromal cells, although controlled in part by the endocrine milieu to which they were exposed prior to culture, does not simulate decidualization in vitro and, therefore, that PA activity is not a marker for decidualization in vitro.
Mol Reprod Dev 1998 Mar
PMID:Secretion of plasminogen activator by cultured rat endometrial stromal cells from uteri differentially sensitized for the decidual cell reaction. 949 79

The syndrome of cancer cachexia is accompanied by several alterations of lipid metabolism, especially that in the liver. In this study we have investigated a possible mechanism whereby the presence of the Walker 256 carcinosarcoma affects hepatic fatty acid oxidative capacity in tumour-bearing rats. Hepatic mitochondrial outer membrane carnitine palmitoyltransferase I (CPT I), generally accepted as the main site of regulation of fatty acid oxidation, was unaffected by the presence of the extra-hepatic tumour. However, mitochondrial inner-membrane carnitine palmitoyltransferase II (CPT II) activity was markedly decreased in mitochondria isolated from the liver of tumour-bearing rats. Immuno-detection by Western blotting using a CPT II-specific antibody identified two bands (corresponding to M(r) 69,000 and 54,000) in tumour-bearing rats whereas only the normal-sized CPT II was present (at the expected M(r) 69,000) in mitochondria from control rats. It is suggested that the emergence of the second, smaller protein may represent a catalytically less active protein that arises in vivo, since its appearance was not affected by the inclusion of proteolysis inhibitors in the mitochondrial preparation buffers. Treatment of the tumour-bearing rats with indomethacin, a prostaglandin (including PGE2) synthesis inhibitor, increased CPT II activity to levels even higher than those found in the control animals. It is suggested that PGE2 may play a role in the control of CPT II expression in the liver of tumour-bearing rats. Indomethacin treatment did not affect either of the two CPT activities of the mitochondria isolated from tumour tissue.
Biochem Mol Biol Int 1998 Jan
PMID:Carnitine palmitoyltransferase II activity is decreased in liver mitochondria of cachectic rats bearing the Walker 256 carcinosarcoma: effect of indomethacin treatment. 950 62


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