Stimulation of hepatocyte DNA synthesis by prostaglandin E<sub>2</sub> and prostaglandin F<sub>2</sub>α additivity with the effect of norepinephrine, and synergism with epidermal growth factor

Refsnes, Magne; Gh, Thoresen; Of, Dajani; Christoffersen, Thoralf

doi:10.1002/jcp.1041590106

Cited by 55 publications

(50 citation statements)

References 46 publications

(58 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Male Wistar rats (170 -230 g) were fed ad libitum. Hepatocytes were isolated by collagenase perfusion as described previously (Refsnes et al, 1994). The hepatocytes were seeded onto Costar plastic culture wells (Corning Life Sciences (Acton, MA) at a density of 2 ϫ 10 4 /cm 2 .…”

Section: Methodsmentioning

confidence: 99%

“…Prostaglandins stimulate proliferation in a number of different cell types (Watanabe et al, 1994;Sheng et al, 2001;Yau and Zahradka, 2003;Chang et al, 2005;Krysan et al, 2005), including neonatal and adult rat hepatocytes (Andreis et al, 1981;Skouteris et al, 1988;Refsnes et al, 1994;Hashimoto et al, 1997;Kimura et al, 2001). In primary cultures of rat hepatocytes, prostaglandins exert a small stimulatory effect on DNA synthesis on their own compared with the strong stimulation of DNA synthesis induced by mitogens, such as epidermal growth factor (EGF), and they act mainly by enhancing the growth stimulatory effect of mitogens .…”

mentioning

confidence: 99%

See 1 more Smart Citation

Prostaglandins Enhance Epidermal Growth Factor-Induced DNA Synthesis in Hepatocytes by Stimulation of E Prostanoid 3 and F Prostanoid Receptors

Meisdalen

Dajani²,

Christoffersen³

et al. 2007

J Pharmacol Exp Ther

Self Cite

View full text Add to dashboard Cite

Prostaglandins stimulate hepatocyte proliferation in vivo and in vitro. We have examined the role of E prostanoid (EP) and F prostanoid receptors (FP) in enhancing the growth-stimulatory effect of epidermal growth factor (EGF) in cultured hepatocytes. The EP2 receptor agonist butaprost had no significant effect on EGF-induced DNA synthesis. EP1 receptor-selective antagonists did not affect the enhancement by prostaglandin E 2 of EGF-stimulated DNA synthesis. Sulprostone, misoprostol, and fluprostenol strongly enhanced DNA synthesis and inhibited glucagon-stimulated cAMP accumulation, indicating that they all activated EP3 receptors. Combining fluprostenol with misoprostol, but not with sulprostone, resulted in partially additive effects on DNA synthesis, suggesting that both EP3 and FP receptors are involved. Combining sulprostone with misoprostol did not result in additive effects on DNA synthesis, suggesting that EP4 receptors were not involved. We conclude that, although a minor effect is exerted by FP receptors, the growth-stimulatory effects of prostaglandins in rat hepatocytes are mediated mainly by EP3 receptors. We have found no evidence of EP1 receptor involvement.

show abstract

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Prostaglandins Enhance Epidermal Growth Factor-Induced DNA Synthesis in Hepatocytes by Stimulation of E Prostanoid 3 and F Prostanoid Receptors

Meisdalen

Dajani²,

Christoffersen³

et al. 2007

J Pharmacol Exp Ther

Self Cite

View full text Add to dashboard Cite

show abstract

“…Other methods DNA synthesis was measured by thymidine incorporation (Refsnes et al, 1994). [6-3 H]-Thymidine ( 3 HTdR) was added to the cultures (1 mCi/ml, 0.125 Ci/ mmol) at 24 and 48 h after plating.…”

Section: Immunoblotsmentioning

confidence: 99%

EGF receptor‐mediated, c‐Src‐dependent, activation of Stat5b is downregulated in mitogenically responsive hepatocytes

Guren

Ødegård

Abrahamsen

et al. 2003

Journal Cellular Physiology

Self Cite

View full text Add to dashboard Cite

Signal transducer and activator of transcription (STAT) proteins may be activated by epidermal growth factor (EGF), but their role in EGF receptor-mediated mitogenic signaling is not clear. We previously showed that Stat5b was activated by EGF in rat hepatocytes in primary monolayer culture. In the present study, we found that EGF induced tyrosine phosphorylation of Stat5b both on Tyr-699, which correlated with specific DNA binding activity, and also on other tyrosine residues. The Src tyrosine kinase inhibitor CGP77675 blocked the EGF-induced activation of Stat5b, but did not affect the Stat5b activation by growth hormone (GH) or prolactin (PRL). The Stat5b response to EGF was most pronounced soon (3 h) after plating (early G 1 ) and at high cell density (50,000 hepatocytes per cm 2 ). However, at this cell density EGF did not stimulate DNA synthesis. In hepatocytes at 24 h of culturing (mid/late G 1 ) with 20,000 cells per cm 2 , EGF induced strong phosphorylation of the EGF receptor, as well as Shc and ERK, and stimulated DNA synthesis, but did not activate Stat5b, although the Stat5b response to GH or PRL was retained. A strong GHinduced Stat5b activation neither influenced the DNA synthesis alone nor enhanced the mitogenic effect of EGF. The results show that EGF induces tyrosine phosphorylation and DNA-binding activity of Stat5b in a manner different from GH and PRL, apparently by a Src-dependent mechanism. The data also provide further evidence that Stat5b is not required for mitogenic signaling from the EGF receptor.

show abstract

“…PGF synthase may be multifunctionally involved in the biosynthesis of PGF and in the binding of bile acids, and PGF synthase in the liver may reduce bile flow. Moreover, PGF 2␣ stimulates hepatocyte DNA synthesis and may have a role in promoting hepatocyte proliferation (35,36). Furthermore, PGF 2␣ and PGD 2 are released from primary Ito cell cultures after stimulation by noradrenaline and ATP (37).…”

mentioning

confidence: 99%

cDNA Cloning, Expression, and Mutagenesis Study of Liver-type Prostaglandin F Synthase

Suzuki

Fujii

Miyano

et al. 1999

Journal of Biological Chemistry

View full text Add to dashboard Cite

F series prostaglandins (PG)1 are widely distributed in various organs of mammals and exhibit a variety of biological activities including constriction of pulmonary arteries (1, 2). PGF 2 is synthesized from PGE 2 , PGD 2 , or PGH 2 by PGE 9-ketoreductase, PGD 11-ketoreductase, or PGH 9,11-endoperoxide reductase, respectively. PGF synthase (EC 1.1.1.188) was purified from bovine lung by Watanabe et al. (3). It forms 9␣,11␤-PGF 2 (4) from PGD 2 (PGD 2 11-ketoreductase activity) and PGF 2␣ from PGH 2 (PGH 2 9,11-endoperoxide reductase activity) on the same molecule in the presence of NADPH (3, 4). This enzyme catalyzes the reduction of other carbonyl compounds including 9,10-phenanthrenequinone (PQ) as well as that of PGD 2 and PGH 2 but does not catalyze the reduction of PGE 2 . Although PGD 2 11-ketoreductase activity was competitively inhibited by PQ, PGH 2 9,11-endoperoxide reductase activity was not inhibited by PGD 2 or PQ (3). PGF synthase belongs to the aldo-keto reductase family. The bovine lung PGF synthase is a monomeric protein with a M r of 36,666 consisting of 323 amino acids, and its amino acid sequence shows high homology compared with that of other aldo-keto reductase family members (5). PGF synthase has two isozymes, one in the lung (3) and the other one in the liver (6), with different K m values for PGD 2 (120 and 10 M, respectively). The regulation by metals, the sensitivity to chloride ions, the inhibition by CuSO 4 and HgCl 2 , and the profile of immuno-precipitation with anti-bovine lung PGF synthase antibody are different between the two isozymes (6). Although Kuchinke et al. (7) isolated a clone (PGFS II) of PGF synthase from bovine liver and determined its amino acid sequence, the 99% similarity with the amino acid sequence of lung PGF synthase and the high K m value for PGD 2 of this recombinant PGFS II indicated that its cDNA was that of the lung-type enzyme even though it had been isolated from liver. Until now, the primary structure of the liver-type PGF synthase and the amino acids related to the affinity for PGD 2

show abstract

Stimulation of hepatocyte DNA synthesis by prostaglandin E₂ and prostaglandin F₂α additivity with the effect of norepinephrine, and synergism with epidermal growth factor

Cited by 55 publications

References 46 publications

Prostaglandins Enhance Epidermal Growth Factor-Induced DNA Synthesis in Hepatocytes by Stimulation of E Prostanoid 3 and F Prostanoid Receptors

Prostaglandins Enhance Epidermal Growth Factor-Induced DNA Synthesis in Hepatocytes by Stimulation of E Prostanoid 3 and F Prostanoid Receptors

EGF receptor‐mediated, c‐Src‐dependent, activation of Stat5b is downregulated in mitogenically responsive hepatocytes

cDNA Cloning, Expression, and Mutagenesis Study of Liver-type Prostaglandin F Synthase

Contact Info

Product

Resources

About

Stimulation of hepatocyte DNA synthesis by prostaglandin E2 and prostaglandin F2α additivity with the effect of norepinephrine, and synergism with epidermal growth factor

Cited by 55 publications

References 46 publications

Prostaglandins Enhance Epidermal Growth Factor-Induced DNA Synthesis in Hepatocytes by Stimulation of E Prostanoid 3 and F Prostanoid Receptors

Prostaglandins Enhance Epidermal Growth Factor-Induced DNA Synthesis in Hepatocytes by Stimulation of E Prostanoid 3 and F Prostanoid Receptors

EGF receptor‐mediated, c‐Src‐dependent, activation of Stat5b is downregulated in mitogenically responsive hepatocytes

cDNA Cloning, Expression, and Mutagenesis Study of Liver-type Prostaglandin F Synthase

Contact Info

Product

Resources

About

Stimulation of hepatocyte DNA synthesis by prostaglandin E₂ and prostaglandin F₂α additivity with the effect of norepinephrine, and synergism with epidermal growth factor