P-134 Okadaic acid, a protein phosphatase inhibitor, enhances ethanol-induced desensitization of receptor-mediated phospholipase C activation in isolated rat hepatocytes

Higashi, Kyoichiro

doi:10.1016/0928-4346(95)90431-6

Cited by 15 publications

(28 citation statements)

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“…Our data thus showed that the addition of excess amount of growth factors reduced the inhibitory effect of ethanol and is agreeable with the report by Higashi and Hoek (1991) demonstrating that ethanol effects were pronounced at low concentrations of agonists but they were not significant at saturating levels in hepatocytes. Figure 5.…”

Section: Discussionsupporting

confidence: 82%

“…Pretreatment of the cells with sublethal concentrations of ethanol markedly inhibited a subsequent stimulation of phospholipase C by vasopressin, angiotensin II, or epidermal growth factor in isolated rat hepatocytes. By contrast, the effects of the alpha 1-adrenergic agonist phenylephrine and of glucagon were not affected by ethanol pretreatment (Higashi and Hoek, 1991). Moreover, ethanol exerts differential effect on the same growth factor depending on the cell type.…”

Section: Discussionmentioning

confidence: 68%

“…However, ethanol does not always modulate the action of all growth factors. Some growth factors are targets of ethanol toxicity but the others are not (Higashi and Hoek, 1991;Luo and Miller, 1997a). Pretreatment of the cells with sublethal concentrations of ethanol markedly inhibited a subsequent stimulation of phospholipase C by vasopressin, angiotensin II, or epidermal growth factor in isolated rat hepatocytes.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, ethanol exerts differential effect on the same growth factor depending on the cell type. Although ethanol inhibits the signaling events by EGF in hepatocytes (Higashi and Hoek, 1991;Saso et al, 1997;Zhang and Farrell, 1999), ethanol did not directly interfere with EGF receptor function in mouse BALB/c3T3 cells (Resnicoff et al, 1996). Ethanol inhibited the proliferation of PDGF-stimulated astrocyte, but some studies could not show the inhibitory effect of ethanol on PDGF-induced increases in cell proliferation (Resnicoff et al, 1994;Guizetti and Costa, 1996) and in DNA synthesis (Tomono and Kiss, 1995;DeVito et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…The blockage of growth factor-mediated cell proliferation by ethanol in several systems elicits the hypothesis that growth factor-induced signaling processes are targets of ethanol toxicity. Included are adenylate cyclase (Hoek et al, 1992;Williams and Kelly, 1993), protein kinase C (Pandy, 1996), protein tyrosine kinases (Miyakawa et al, 1997, Resnicoff et al, 1993, Thurston and Shukla, 1992, MAPKs (Roivainen et al, 1995;Reddy and Shukla, 1996;Chen et al, 1998;Tombes et al, 1998;Reddy and Shukla, 2000), phospholipase C and D (Higashi and Hoek, 1991;Hoek et al, 1992;Thurston and Shukla, 1992;Saso et al, 1997;Zhang and Farrell, 1999), transcription factors such as NF-κB (Zeldin et al, 1996) and STAT3 (Chen et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

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Effect of short-term ethanol on the proliferative response of Swiss 3T3 cells to mitogenic growth factors

Yeo¹,

Lim²,

Park³

2000

Exp Mol Med

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Both adaptive and deleterious responses of cells to ethanol are likely triggered by short-term interactions of the cells with ethanol. Many studies have demonstrated the direct effect of ethanol on growth factor-stimulated cell proliferation. Using Swiss 3T3 cells whose growth was inhibited by ethanol in a concentration-dependent manner, we further investigated the molecular mechanisms of acute ethanol treatment by examining its effect on EGF-and PDGF-mediated cellular signaling systems for the mitogenic function. Tyrosine autophosphorylation of the growth factor receptors was partially prevented by ethanol in intact cells. When ethanol was included before or after EGF stimulation, no effect on the receptor signaling was observed. Here we also report that ethanol inhibits activation of ERK induced by both EGF and PDGF. EGF-induced JNK activation was reduced but PDGF-induced rapid JNK activation was delayed by the addition of ethanol. The balance between its inhibitory and stimulatory effect on the signaling molecules might determine the rate of cell growth.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Effect of short-term ethanol on the proliferative response of Swiss 3T3 cells to mitogenic growth factors

Yeo¹,

Lim²,

Park³

2000

Exp Mol Med

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Papaverine inhibits bile acid excretion in isolated perfused rat liver

et al. 1994

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We investigated the effects of papaverine on bile acid excretion into bile in the presence of infusions of taurocholic acid, tauroursodeoxycholic acid, taurochenodeoxycholic acid and taurodehydrocholic acid in a single-pass, isolated perfused rat liver model. Although continuous infusion of papaverine (1.6 mumol/min) did not reduce bile acid excretion in the presence of low-dose (1.0 mumol/min) infusions of taurocholic acid or tauroursodeoxycholic acid, papaverine significantly inhibited biliary excretion of bile acids in the presence of low-dose taurochenodeoxycholic acid (-50%) and high-dose (3.0 mumol/min) taurocholic acid (-54%), tauroursodeoxycholic acid (-37%) and taurodehydrocholic acid (-31%). During continuous infusion of taurocholic acid (3 mumol/min), a 15-min infusion of papaverine (3.2 mumol/min) reduced bile acid excretion significantly; however, total uptake of bile acid was slightly decreased by the papaverine infusion. Bile acid excretion increased over the baseline value after the papaverine infusion was stopped and then returned to baseline. These results suggest that papaverine does not affect the uptake phase of bile acids at the sinusoidal membrane but may affect the intracellular transport phase or the excretory phase at the bile canalicular membrane. When taurocholic acid was infused at a constant rate of 3 mumol/min for 20 min without papaverine and then stopped, bile acid excretion decreased gradually and was nearly zero by 52 min. Cumulative bile acid excretion in the 52 min after the end of the infusion reached 3.3 +/- 0.2 mumol/gm liver and represented the storage capacity of the liver.(ABSTRACT TRUNCATED AT 250 WORDS)

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Ethyl pyruvate modulates acute inflammatory reactions in human endothelial cells in relation to the NF‐κB pathway

Johansson-Haque

Okret

et al. 2008

British J Pharmacology

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Background and purpose: Endothelial cell activation plays a critical role in regulating leukocyte recruitment during inflammation and infection. Ethanol (EtOH) reduces host defence systems, including cell adhesion. However, well-known side effects of EtOH limit its clinical use as an anti-inflammatory drug. Instead, ethyl pyruvate (EtP) may represent a better alternative. Here, we compared effects of EtP and EtOH on neutrophil recruitment and activation of human umbilical vein endothelial cells (HUVECs). Experimental approach: Adhesion of neutrophils to HUVEC monolayers, surface expression of intercellular cell adhesion molecule, E-selectin, vascular cell adhesion molecule, release of interleukin (IL)-8 and granulocyte colony-stimulating factor (G-CSF) from HUVECs were assessed as well as translocation of interleukin-1 receptor-associated kinase (IRAK-1), the nuclear factor-kappa B (NF-kB) subunits p50, p65 and IkB-a. NF-kB activation was analysed with a luciferase reporter plasmid. Cells were stimulated with IL-1b, lipopolysaccharide (LPS) or tumour necrosis factor-a. Key results: EtP was several-fold more potent than EtOH in reducing adhesion of neutrophils to activated HUVECs, generation of IL-8 or G-CSF and surface expression of the adhesion molecules. This last reaction was decreased by EtP even when added after cytokines or LPS. Translocation of IRAK-1, IkBa and the NF-kB p65 subunit to the HUVEC nucleus was inhibited by EtP for all stimuli, whereas the diminished p50 translocation was stimulus specific. When p65 was constitutively expressed in Cos7 cells, stimulation of an NF-kB-dependent reporter gene was not affected by EtP, suggesting that EtP acted upstream of gene activation. Conclusions and implications: EtP impedes adhesive, secretory and signalling events typical of the early inflammatory response in endothelial cells, suggesting EtP as a possible treatment for acute inflammatory conditions.

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P-134 Okadaic acid, a protein phosphatase inhibitor, enhances ethanol-induced desensitization of receptor-mediated phospholipase C activation in isolated rat hepatocytes

Cited by 15 publications

References 0 publications

Effect of short-term ethanol on the proliferative response of Swiss 3T3 cells to mitogenic growth factors

Effect of short-term ethanol on the proliferative response of Swiss 3T3 cells to mitogenic growth factors

Papaverine inhibits bile acid excretion in isolated perfused rat liver

Ethyl pyruvate modulates acute inflammatory reactions in human endothelial cells in relation to the NF‐κB pathway

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