The Role of Src Kinase in the Potentiation by Ethanol of Cytokine- and Endotoxin-Mediated Nitric Oxide Synthase Expression in Rat Hepatocytes

Kuo, Min-Liang; Chau, Yat‐Pang; Wang, Jyh-Horng; Lin, Pei‐Jung

doi:10.1124/mol.52.3.535

Cited by 16 publications

(10 citation statements)

References 34 publications

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“…40 Discrepant findings with different protein tyrosine kinase inhibitors as shown here for genistein and herbimycin A were also recently described for the regulation of inducible nitric oxide synthase mRNA in primary rat hepatocytes, 30 suggesting different target proteins for each inhibitor. However, exactly where genistein and herbimycin A interfere with the 2 separate PAI-1 inductory pathways for PMA and IL-␣ is not clear at present and requires further research.…”

Section: 39mentioning

confidence: 71%

“…First, we examined the effect of another protein tyrosine kinase inhibitor, herbimycin A. Herbimycin A, like genistein, was previously demonstrated to block IL-1␣-stimulated PAI-1 gene expression in cultured human endothelial cells, 20 but different target proteins have been suggested for each inhibitor. 30 As shown in Figure 4, herbimycin A (0.3 g/mL) potently inhibited IL-1␣-induced PAI-1 mRNA expression, but unlike genistein, was ineffective toward PMA-stimulated PAI-1 and CAT mRNA induction. Also in contrast to genistein, herbimycin A had no effect on c-jun or c-fos mRNA induced by IL-1␣ or PMA (data not shown).…”

Section: Effect Of Herbimycin a Ro 31-8220 Pd98059 And Sb 203580 Omentioning

confidence: 81%

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On the Role of c-Jun in the Induction of PAI-1 Gene Expression by Phorbol Ester, Serum, and IL-1α in HepG2 Cells

Arts¹,

Grimbergen²,

Toet³

et al. 1999

ATVB

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Abstract-We have characterized the regulation of plasminogen activator inhibitor-1 (PAI-1) gene expression by phorbol 12-myristate 13-acetate (PMA), serum, and interleukin-1␣ (IL-1␣) in the human hepatoma cell line HepG2. PMA, serum, and IL-1␣ induced a rapid and transient 28-fold (PMA), 9-fold (serum), and 23-fold (IL-1␣) increase in PAI-1 mRNA, peaking after Ϸ4 hours. These inductions of PAI-1 mRNA accumulation were reduced by pretreatment of the HepG2 cells with the protein tyrosine kinase inhibitor genistein. Conversely, stimulation of tyrosine phosphorylation by sodium orthovanadate, an inhibitor of protein tyrosine phosphatases, caused an increase in PAI-1 mRNA levels. The effects of PMA, serum, and IL-1␣ on PAI-1 mRNA expression have been compared with their ability to modulate the expression of a chloramphenicol acetyltransferase (CAT) reporter plasmid, which was under control of the Ϫ489 to ϩ75 region of the PAI-1 promoter, and stably transfected into HepG2 cells. This region of the PAI-1 promoter was previously found to contain a tetradecanoyl phorbol acetate-response element (TRE; between Ϫ58 and Ϫ50) necessary for PMA responsiveness and with a high affinity for c-Jun homodimers. Whereas incubation of these transfected HepG2 cells with PMA and serum showed an induction profile of CAT mRNA similar to that of PAI-1 mRNA, hardly any induction of CAT mRNA was found with IL-1␣. In line with these findings, IL-1␣ poorly induced c-Jun homodimer binding to the PAI-1 TRE in gel mobility-shift assays. Pretreatment of HepG2 cells with the protein kinase C inhibitor Ro 31-8220 or the mitogen-activated protein kinase kinase (MAPKK) 1,2 activity blocker PD98059 selectively suppressed the induction of PAI-1 (and CAT) expression by PMA, but not that by IL-1␣. In contrast, the protein tyrosine kinase inhibitor herbimycin A blocked PAI-1 mRNA induction by IL-1 ␣ only. We propose 2 separate PAI-1 inductory pathways for PMA and IL-1␣ in HepG2, both involving protein tyrosine kinase activation; the serum-induced signaling pathway may

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Section: 39mentioning

confidence: 71%

Section: Effect Of Herbimycin a Ro 31-8220 Pd98059 And Sb 203580 Omentioning

confidence: 81%

On the Role of c-Jun in the Induction of PAI-1 Gene Expression by Phorbol Ester, Serum, and IL-1α in HepG2 Cells

Arts¹,

Grimbergen²,

Toet³

et al. 1999

ATVB

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“…The PTK p59 fyn is a possible target for these inhibitors, because it was shown to be involved in NF-B-mediated activation of the HIV long terminal repeat promoter (31). Discrepant findings with different PTK inhibitors as shown here for genistein and herbimycin A were recently described for the regulation of inducible nitric-oxide synthase mRNA in primary rat hepatocytes involving the PTK pp60 c-src (25), suggesting different target proteins for each inhibitor.…”

Section: Inhibition Of Cytokine-induced Nf-b Transactivation 6608mentioning

confidence: 90%

IκBα Degradation and Nuclear Factor-κB DNA Binding Are Insufficient for Interleukin-1β and Tumor Necrosis Factor-α-induced κB-dependent Transcription

Bergmann¹,

Hart²,

Lindsay

et al. 1998

Journal of Biological Chemistry

182

136

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Two closely related IB␣ kinases as well as the upstream kinase, NIK, which integrates interleukin-1␤ (IL-1␤)-and tumor necrosis factor (TNF)-␣-dependent acti-vation of the transcription factor NF-B have recently been described. However, in this emerging pathway the role of previously identified components of cytokineinduced NF-B activation, namely phosphatidylcholinespecific phospholipase C and protein kinase C, remains unclear. We now show that, in A549 human alveolar epithelial cells, the activation of a stably transfected NF-B-dependent reporter gene by TNF-␣ and IL-1␤ is completely blocked by the phosphatidylcholine-specific phospholipase C inhibitor D609 and the protein kinase C inhibitor RO31-8220. However, IL-1␤-induced IB␣ degradation as well as NF-B nuclear translocation and DNA binding, as determined by Western blot and electro-mobility shift assay, respectively, are not affected by these inhibitors. A similar effect, although less pronounced, is observed with the p38 mitogen-activated protein kinase inhibitor SB 203580. On the basis of these data we propose the existence of a second signaling pathway induced by IL-1␤ and TNF-␣ that is activated in parallel to the cascade leading to IB␣ degradation and is specifically required for NF-B-dependent transcriptional competency.

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“…24 However, NAC failed to inhibit iNOS induction in rat hepatocytes. 26 In hepatocytes, intracellular glutathione was reported to be required for cytokine-induced NF-B activation and iNOS expression because the iNOS induction was prevented by glutathione depletion and could be restored by addition of NAC. 27,28 The results from the present study showed no obvious effect of NAC on cytokine activation of NF-B, which was consistent with previous reports 29 that indicated no inhibitory effect of NAC on IL-1-and TNF-activated NF-B in some cell lines.…”

Section: Discussionmentioning

confidence: 99%

N -Acetyl- l -Cysteine Enhances Interleukin-1β–Induced Nitric Oxide Synthase Expression

1999

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Abstract-The effect of N-acetyl-L-cysteine on interleukin-1␤-induced nitric oxide synthase expression was studied in rat vascular smooth muscle cells to determine if the reduction/oxidation state would modulate cytokine-induced changes. Interleukin-1␤ induced the production of nitrite, a stable metabolite of nitric oxide in a time-and dose-dependent manner. Cytokine-induced nitrite production was enhanced by the addition of N-acetyl-L-cysteine in a dose-dependent manner, with a Ͼ50% increase produced by the addition of 1 mmol/L N-acetyl-L-cysteine. There was no influence on nitrite production when the cells were treated with N-acetyl-L-cysteine alone. Northern and Western blot analyses revealed that the upregulation of interleukin-1␤-induced nitric oxide production by N-acetyl-L-cysteine resulted from an enhanced expression of inducible nitric oxide synthase. Interferon-␥ or tumor necrosis factor-␣ when used alone had no influence on nitrite production in the absence or presence of N-acetyl-L-cysteine. Nitrite accumulation was higher by the cells treated with interleukin-1␤ combined with either interferon-␥ or tumor necrosis factor-␣ compared with those treated with interleukin-1␤ alone. N-Acetyl-L-cysteine upregulated nitrite production and inducible nitric oxide synthase expression induced by combination treatment with interleukin-1␤ and either interferon-␥ or tumor necrosis factor-␣. However, N-acetyl-L-cysteine had no significant influence in cytokine-induced activation of nuclear factor-B or signal transducer and activator of transciption-1, as assessed by electrophoretic mobility shift assays. These results demonstrate that N-acetyl-L-cysteine possibly acted as a thiol-containing reducing agent and facilitated the expression of inducible nitric oxide synthase in rat vascular smooth muscle cells by cytokines through a mechanism that is independent of nuclear factor-B or signal transducer and activator of transciption-1. (Hypertension. 1999;34:574-579.)

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The Role of Src Kinase in the Potentiation by Ethanol of Cytokine- and Endotoxin-Mediated Nitric Oxide Synthase Expression in Rat Hepatocytes

Cited by 16 publications

References 34 publications

On the Role of c-Jun in the Induction of PAI-1 Gene Expression by Phorbol Ester, Serum, and IL-1α in HepG2 Cells

On the Role of c-Jun in the Induction of PAI-1 Gene Expression by Phorbol Ester, Serum, and IL-1α in HepG2 Cells

IκBα Degradation and Nuclear Factor-κB DNA Binding Are Insufficient for Interleukin-1β and Tumor Necrosis Factor-α-induced κB-dependent Transcription

N -Acetyl- l -Cysteine Enhances Interleukin-1β–Induced Nitric Oxide Synthase Expression

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