scholarly journals Ptgs2 activation by endotoxin mediates the decrease in Igf1, but not in Igfbp3, gene expression in the liver

2008 ◽  
Vol 198 (2) ◽  
pp. 385-394 ◽  
Author(s):  
A I Martín ◽  
M López-Menduiña ◽  
E Castillero ◽  
M Granado ◽  
M A Villanúa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Direct Action ◽  
Primary Cultures ◽  
Inhibitory Effect ◽  
Liver Cells ◽  
Male Wistar Rats ◽  
Igf Binding

The aim of this work was to analyse the role of cyclooxygenase-2 (Ptgs2) in endotoxin-induced decrease in Igf1 and Igf binding protein-3 (Igfbp3). For this purpose, male Wistar rats were injected with lipolysaccharide (LPS) and/or the Ptgs2 inhibitor meloxicam. LPS induced a significant decrease (P<0.01) in serum concentrations of Igf1 and Igfbp3 and their mRNAs in the liver. Meloxicam administration prevented the inhibitory effect of LPS injection on serum Igf1 and its liver mRNA. By contrast, meloxicam administration was unable to modify the inhibitory effect of LPS on Igfbp3. LPS injection also induced a decrease in GH receptor (Ghr) mRNA in the liver, and meloxicam attenuated this effect. In order to elucidate a direct action of the Ptgs2 inhibitor on the liver cells, the effect of LPS and/or meloxicam was studied in primary cultures of hepatocytes with non-parenchymal cells. LPS decreased Igf1 and Ghr but not Igfbp3 gene expression in liver cells in culture. Meloxicam administration attenuated the inhibitory effect of LPS on Igf1 mRNA, whereas it did not modify the decrease in Ghr mRNA after LPS. The effect of meloxicam on the LPS response does not seem to be mediated by changes in nitric oxide or tumour necrosis factor (Tnf) production, since meloxicam did not modify the stimulatory effect of LPS on nitric oxide or Tnfα gene expression both in vivo and in vitro. All these data suggest that LPS-induced Ptgs2 activation decreases Igf1 gene expression in liver cells.

scholarly journals Evidence for a transient inhibitory effect of insulin on GLUT2 expression in the liver: studies in vivo and in vitro

1993 ◽  
Vol 293 (1) ◽  
pp. 119-124 ◽  
Author(s):  
C Postic ◽  
R Burcelin ◽  
F Rencurel ◽  
J P Pegorier ◽  
M Loizeau ◽  
...  
Keyword(s):  
Gene Expression ◽  
Glucose Transporter ◽  
Primary Cultures ◽  
Rat Hepatocytes ◽  
Inhibitory Effect ◽  
Mrna Concentration ◽  
Glut2 Gene ◽  
Effect Of Glucose

The glucose transporter GLUT2 is expressed predominantly in the liver. Previous studies have shown that glucose increases GLUT2 mRNA concentration in primary cultures of rat hepatocytes. Since insulin controls the glucose metabolism in the liver, it could be involved in the regulation of GLUT2 gene expression. In vivo, hyperinsulinaemia induced a transient inhibitory effect on liver GLUT2 gene expression, the maximal inhibition of GLUT2 mRNA concentration (93 +/- 6%) being observed after 6 h. When hyperglycaemia was associated with hyperinsulinaemia, the decrease in liver GLUT2 mRNA concentration was partially prevented. The respective effects of glucose and insulin were studied in vitro by primary culture of rat hepatocytes. Insulin alone exerted a transient inhibitory effect on GLUT2 mRNA concentration. When insulin and glucose (10-20 mM) were associated, the stimulatory effect of glucose on GLUT2 gene expression was predominant. In conclusion, the present study shows that GLUT2 mRNA concentration was conversely regulated by insulin and glucose, both in vitro and in vivo.

scholarly journals Comparative Proteomic Identification of Protein Disulphide Isomerase A6 Associated with Tert-Butylhydroperoxide-Induced Liver Injury in Rat Hepatocytes

2018 ◽  
Vol 45 (5) ◽  
pp. 1915-1926 ◽  
Author(s):  
Chien-Heng Shen ◽  
Shui-Yi Tung ◽  
Wen-Shih Huang ◽  
Kam-Fai Lee ◽  
Yung-Yu Hsieh ◽  
...  
Keyword(s):  
Liver Injury ◽  
Cell Viability ◽  
Er Stress ◽  
Primary Cultures ◽  
Liver Cells ◽  
Cytochrome C Release ◽  
Dapi Staining ◽  
Tert Butylhydroperoxide

Background/Aims: Oxidants are important human toxicants. They have been implicated in the occurrence and development of liver diseases. Increased intracellular tert-butylhydroperoxide (t-BHP) may be critical for oxidant toxicity, and is commonly used for evaluating mechanisms involving oxidative stress, but the method remains controversial. Methods: Primary cultures of hepatocytes as well as human Hep G2 and mouse FL83B liver cells were obtained. Cell viability was measured by annexin V–FITC/propidium iodide and DAPI staining to determine the effects of t-BHP treatment on acute liver injury. A proteomic assay provided information that was used to identify the differentially expressed proteins following t-BHP treatment; immunohistochemistry and western blotting were performed to detect the expression of PDIA6 activity in apoptotic and endoplasmic reticulum (ER) stress pathways. Results: Our results demonstrate that t-BHP treatment of liver cells increased cell cytotoxicity and the generation of reactive oxygen species. This treatment also increased the level of PDIA6; this was validated in vitro and in vivo based on a comparison of t-BHP-treated and -untreated groups. Treatment of mouse liver FL83B cells with t-BHP activated caspase 3, increased the expression of apoptotic molecules, caused cytochrome c release, and induced Bcl-2, Bax and IRE1α/TRAF2 complex formation. t-BHP-dependent induction of apoptosis was accompanied by sustained phosphorylation of the IRE1α/ASK1/JNK1/2/p38 pathways and PDIA6 expression. Furthermore, t-BHP induced liver FL83B cell viability and apoptosis by upregulating the levels of PDIA6; this process could be involved in the activation of the IRE1α/ASK1/JNK1/2/p38 signalling pathways. Conclusions: We conclude that t-BHP induced an apoptosis cascade and ER stress in hepatocytes by upregulation of PDIA6, providing a new mechanism underlying the effects of t-BHP on liver injury.

Hydrogen sulfide downregulates the aortic l-arginine/nitric oxide pathway in rats

2007 ◽  
Vol 293 (4) ◽  
pp. R1608-R1618 ◽  
Author(s):  
Bin Geng ◽  
Yuying Cui ◽  
Jing Zhao ◽  
Fang Yu ◽  
Yi Zhu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Hydrogen Sulfide ◽  
Umbilical Vein ◽  
Transcript Abundance ◽  
Inhibitory Effect ◽  
Akt Phosphorylation ◽  
Enos Activity ◽  
Nos Inhibitors

The aim of the present study was to investigate the effect of hydrogen sulfide (H2S) signaling by nitric oxide (NO) in isolated rat aortas and cultured human umbilical vein endothelial cells (HUVECs). Both administration of H2S and NaHS, as well as endogenous H2S, reduced NO formation, endothelial nitric oxide synthase (eNOS) activity, eNOS transcript abundance, and l-arginine (l-Arg) transport (all P < 0.01). The kinetics analysis of eNOS activity and l-Arg transport showed that H2S reduced Vmax values (all P < 0.01) without modifying Km parameters. Use of selective NOS inhibitors verified that eNOS [vs. inducible NOS (iNOS) and neuronal NOS (nNOS)] was the specific target of H2S regulation. H2S treatment (100 μmol/l) reduced Akt phosphorylation and decreased eNOS phosphorylation at Ser1177. H2S reduced l-Arg uptake by inhibition of a system y+ transporter and decreased the CAT-1 transcript. H2S treatment reduced protein expression of eNOS but not of nNOS and iNOS. Pinacidil (KATP channel opener) exhibited the similar inhibitory effects on the l-Arg/NOS/NO pathway. Glibenclamide (KATP channel inhibitor) partly blocked the inhibitory effect of H2S and pinacidil. An in vivo experiment revealed that H2S downregulated the vascular l-Arg/eNOS/NO pathway after intraperitoneal injection of NaHS (14 μmol/kg) in rats. Taken together, our findings suggest that H2S downregulates the vascular l-Arg/NOS/NO pathway in vitro and in vivo, and the KATP channel could be involved in the regulatory mechanism of H2S.

scholarly journals Inhibitory effect of nitric oxide on the replication of a murine retrovirus in vitro and in vivo.

1995 ◽  
Vol 69 (11) ◽  
pp. 7001-7005 ◽  
Author(s):  
K Akarid ◽  
M Sinet ◽  
B Desforges ◽  
M A Gougerot-Pocidalo
Keyword(s):  
Nitric Oxide ◽  
Inhibitory Effect

Metabolic Activity in Primary Cultures of Fish Hepatocytes

2001 ◽  
Vol 29 (3) ◽  
pp. 251-257 ◽  
Author(s):  
Helmut Segner ◽  
Jean-Pierre Cravedi
Keyword(s):  
Primary Cultures ◽  
Hepatic Metabolism ◽  
Liver Cells ◽  
In Vivo Studies ◽  
Glutathione S Transferase ◽  
Biotransformation Enzymes ◽  
Cytochrome P4501a ◽  
Isolated Liver Cells

In aquatic toxicology, isolated liver cells from fish can be used as a tool to generate initial information on the hepatic metabolism of xenobiotics, and on the mechanisms of xenobiotic activation or deactivation. This isolation of teleost liver cells is achieved by enzymic dissociation, and monolayer cultures of fish hepatocytes in serum-free medium maintain good viability for 3–8 days. During in vitro culture, fish liver cells express stable levels of phase I and phase II enzymes, such as cytochrome P4501A or glutathione S-transferase, and the cells show an induction of biotransformation enzymes after exposure to xenobiotics. The xenobiotic metabolite pattern produced by fish hepatocytes in vitro is generally similar to that observed in vivo. Limitations to more-intensive application of cultured fish hepatocytes as a screen in aquatic hazard assessment are partly due to the rather limited scope of existing studies, i.e. the focus on one particular species (rainbow trout), and on one particular biotransformation enzyme (cytochrome P4501A), as well as a lack of comparative in vitro/in vivo studies.

Nitric oxide as a putative nonadrenergic noncholinergic inhibitory transmitter in the canine pylorus in vivo

1992 ◽  
Vol 262 (4) ◽  
pp. G695-G702 ◽  
Author(s):  
H. D. Allescher ◽  
G. Tougas ◽  
P. Vergara ◽  
S. Lu ◽  
E. E. Daniel
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Vagal Stimulation ◽  
Inhibitory Effect ◽  
Field Stimulation ◽  
Neural Inhibition ◽  
Anesthetized Dogs ◽  
Inhibitory Transmitter

Antropyloroduodenal motility was recorded in seven anesthetized dogs to assess the role of nitric oxide and L-arginine metabolites in nonadrenergic noncholinergic (NANC) mediation of pyloric relaxation. Pyloric activity induced by duodenal field stimulation was inhibited by antral field stimulation and electrical vagal stimulation. Intra-arterial NG-L-arginine-methyl-ester (L-NAME) reduced the inhibition from antral or vagal stimulation (P less than 0.05). Intravenous infusion of L-NAME also blocked the inhibitory effect of vagal and antral stimulation but left the tetrodotoxin-insensitive action of intra-arterial vasoactive intestinal peptide (VIP) and sodium nitroprusside unchanged. L-Arginine reversed the effect of L-NAME whereas D-arginine did not. L-NAME enhanced pyloric contractions to intra-arterial acetylcholine. The NANC inhibition of the substance P-stimulated pyloric response in vitro was blocked by L-NAME and reversed by addition of L-arginine. Sodium nitroprusside was effective as a relaxant in vitro but VIP was not. These data suggest that metabolites of L-arginine mediate neural inhibition of canine pyloric motor activity.

Inhaled nitric oxide increases surfactant protein gene expression in the intact lamb

2003 ◽  
Vol 285 (3) ◽  
pp. L628-L633 ◽  
Author(s):  
Regan B. Stuart ◽  
Boaz Ovadia ◽  
Vincent V. Suzara ◽  
Patrick A. Ross ◽  
Stephan Thelitz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Dna Content ◽  
Protein Gene ◽  
Surfactant Protein ◽  
Inhaled Nitric Oxide ◽  
Mrna Content ◽  
Lung Biopsies

Inhaled nitric oxide (iNO) is used to treat a number of disease processes. Although in vitro data suggest that nitric oxide (NO) alters surfactant protein gene expression, the effects in vivo have not been studied. The objective of this study was to evaluate the effects of iNO on surfactant protein (SP)-A, -B, and -C gene expression in the intact lamb. Thirteen 4-wk-old lambs were mechanically ventilated with 21% oxygen and received iNO at 40 ppm ( n = 7) or vehicle gas ( n = 6) for 24 h. Peripheral lung biopsies were obtained at 0, 12, and 24 h and analyzed for surfactant mRNA, protein, and total DNA content. Inhaled NO increased SP-A and SP-B mRNA content by 80% from 0 to 12 h and by 78 and 71%, respectively, from 0 to 24 h. There was an increase in SP-A and SP-B protein content by 45% from 0 to 12 h, and a decrease by 70 and 65%, respectively, from 0 to 24 h. DNA content was unchanged. The mechanisms and physiological effects of these findings warrant further investigation.

Gene expression profiling of liver cells after copper overload in vivo and in vitro reveals new copper-regulated genes

2007 ◽  
Vol 12 (4) ◽  
pp. 495-507 ◽  
Author(s):  
Patricia Muller ◽  
Harm van Bakel ◽  
Bart van de Sluis ◽  
Frank Holstege ◽  
Cisca Wijmenga ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Liver Cells ◽  
Copper Overload

MODE OF ACTION OF CLOMIPHENE

1969 ◽  
Vol 60 (4) ◽  
pp. 635-644 ◽  
Author(s):  
J. Hammerstein
Keyword(s):  
Mode Of Action ◽  
Specific Activity ◽  
Direct Action ◽  
Clomiphene Citrate ◽  
Inhibitory Effect ◽  
Isotopic Dilution ◽  
Corpora Lutea ◽  
Isolation And Purification

ABSTRACT The in vitro influence of clomiphene citrate on the incorporation of acetate-1-14C into progesterone by slices of human corpora lutea was studied in 10 experiments using the reverse isotopic dilution technique for the isolation and purification of radioactive progesterone, followed in most instances by crystallization to constant specific activity. As a clear-cut and reproducible result, the formation of progesterone from labelled acetate was considerably diminished in the presence of clomiphene citrate independent of whether the tissues originated from the menstrual cycle or from normal as well as ectopic pregnancies. This inhibitory effect on the biosynthesis of progesterone was intensified by increasing the concentration of clomiphene in the medium. It was demonstrable after 13.3 minutes of incubation as well as after 6 hours. No obvious interference of clomiphene with the stimulating action of HCG on steroidogenesis was found. These findings point to a direct action of clomiphene on the ovary which might also have some bearing on the mode of action of clomiphene in vivo.

Inhibition of gastric H+ secretion, K+-ATPase and K+-phosphatase by estradiol in vivo and in vitro

1982 ◽  
Vol 60 (5) ◽  
pp. 680-684 ◽  
Author(s):  
L. Limlomwongse ◽  
P. Piyachaturawat
Keyword(s):  
Gastric Mucosa ◽  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Enzyme Activities ◽  
Direct Action ◽  
Inhibitory Effect ◽  
Secretory Rate ◽  
Dose Dependent

The effect of estrogen on the gastric acid secretion and H+-transporting enzymes, K+ -ATPase and K+-phosphatase, were investigated in the rat. The maximum H+ secretory rate in response to 1 mM histamine was significantly reduced (P < 0.05) in both the isolated gastric mucosa obtained from the rats treated with estradiol in vivo for 7 days and the mucosa directly incubated in vitro with estradiol. The inhibitory effect on the gastric enzyme activities in vitro showed a dose-dependent pattern of a noncompetitive type. The result suggested that estradiol may have a direct action on the gastric H+ secretion by inhibiting the H+ transport enzyme activities.

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