Alcohol and Cytokine‐inducible Transcription Factors

Zeldin, Gillian; Yang, Shi Qi; Yin, Meizhen; Lin, Hui-Kuan; Rai, Rudra; Diehl, Anna Mae

doi:10.1111/j.1530-0277.1996.tb01710.x

Cited by 61 publications

(53 citation statements)

References 31 publications

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“…Exposure to ethanol for 16 h increased the basal JNK activity but there was no change in agonist-induced JNK activation. Whereas chronic ethanol intake for 60 days inhibited the activation of ERK, p38, and JNK induced either by partial hepatectomy or by treatment with various agonists (Zeldin et al, 1996;Chen et al, 1998). In the present study, we observed that acute ethanol treatment for 5-10 min inhibited growth factor-stimulated tyrosine phosphorylation and ERK activation even in the absence of any preincubation with ethanol.…”

Section: Discussionsupporting

confidence: 60%

“…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: 60%

Section: Introductionmentioning

confidence: 99%

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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“…JNK Immune Complex Assay-Jnk-1 activity was evaluated as we have described (15,23). Briefly, antibodies for Jnk-1 (Santa Cruz Diagnostics) were used to immunoprecipitate Jnk-1 from hepatic nuclear extracts; the Jnk-1 substrate, GST-c-Jun fusion peptide (Santa Cruz Diagnostics) and [␥- After separating the reaction products by electrophoresis on 10% acrylamide gels and transfer to nylon membranes by capillary blotting, Jnk-1 activity was quantified by PhosphorImager analysis of the phosphorylated substrate using ImageQuant software (Molecular Dynamics, Sunnyvale, CA).…”

Section: Methodsmentioning

confidence: 99%

Chronic Ethanol Exposure Potentiates Lipopolysaccharide Liver Injury Despite Inhibiting Jun N-terminal Kinase and Caspase 3 Activation

Koteish

Yang

Lin

et al. 2002

Journal of Biological Chemistry

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Although ethanol is known to sensitize hepatocytes to tumor necrosis factor (TNF) lethality, the mechanisms involved remain controversial. Recently, others have shown that adding TNF␣ to cultures of ethanol-pretreated hepatocytes provokes the mitochondrial permeability transition, cytochrome c release, procaspase 3 activation, and apoptosis. Although this demonstrates that ethanol can sensitize hepatocytes to TNF-mediated apoptosis, the hepatic inflammation and ballooning hepatocyte degeneration that typify alcohol-induced liver injury suggest that other mechanisms might predominate in vivo. To evaluate this possibility, acute responses to lipopolysaccharide (LPS), a potent inducer of TNF␣, were compared in mice that had been fed either an ethanol-containing or control diet for 5 weeks. Despite enhanced induction of cytokines such as interleukin (IL)-10, IL-15, and IL-6 that protect hepatocytes from apoptosis, ethanol-fed mice exhibited a 4 -5-fold increase in serum alanine aminotransferase after LPS, confirming increased liver injury. Six h post-LPS histology also differed notably in the two groups, with control livers demonstrating only scattered apoptotic hepatocytes, whereas ethanol-exposed livers had large foci of ballooned hepatocytes, inflammation, and scattered hemorrhage. No caspase 3 activity was noted during the initial 6 h after LPS in ethanol-fed mice, but this tripled by 1.5 h after LPS in controls. Procaspase 8 cleavage and activity of the apoptosis-associated kinase, Jun N-terminal kinase, were also greater in controls. In contrast, ethanol exposure did not inhibit activation of cytoprotective mitogen-activated protein kinases and AKT or attenuate induction of the anti-apoptotic factors NF-B and inducible nitric oxide synthase. Consistent with these responses, neither cytochrome c release, an early apoptotic response, nor hepatic oligonucleosomal DNA fragmentation, the ultimate consequence of apoptosis, was increased by ethanol. Thus, ethanol exacerbates TNF-related hepatotoxicity in vivo without enhancing caspase 3-dependent apoptosis.

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“…Ethanol modulates the activity of several important signaling molecules (32) including ERK1/2, p38 MAPK (33), JNK (33,34), and the transcription factors NFB (35) and Egr-1.…”

mentioning

confidence: 99%

Stabilization of Tumor Necrosis Factor α mRNA by Chronic Ethanol

Kishore

McMullen

Nagy

2001

Journal of Biological Chemistry

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Increased expression of tumor necrosis factor ␣ (TNF␣) in response to chronic ethanol has been implicated in the pathogenesis of alcoholic liver disease. However, the molecular mechanisms by which ethanol increases the levels of TNF␣ are not well characterized. Utilizing Kupffer cells isolated from rats fed an ethanol containing diet and a murine macrophage cell line, RAW264.7, exposed to ethanol in culture, we have demonstrated that exposure to chronic ethanol results in an enhanced expression of lipopolysaccharide (LPS)-induced TNF␣. While chronic ethanol had no effect on the rate of LPS-induced TNF␣ transcription as measured by nuclear run-on experiments, TNF␣ mRNA half-life was increased by chronic ethanol. Chronic ethanol also potentiated the activation of LPS-induced p38 mitogenactivated protein (MAP) kinase in Kupffer cells, as well as in RAW264.7 cells. Specific inhibition of p38 MAP kinase activation by SB203580 in Kupffer cells or by overexpression of dominant negative p38 MAP kinase in RAW264.7 cells blocked ethanol-mediated TNF␣ mRNA stabilization. Furthermore, using chimeric reporter constructs, we have shown that A ؉ U-rich elements in the 3-untranslated region of TNF␣ mRNA are not sufficient to impart ethanol-mediated stabilization on TNF␣ mRNA.

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Alcohol and Cytokine‐inducible Transcription Factors

Cited by 61 publications

References 31 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

Chronic Ethanol Exposure Potentiates Lipopolysaccharide Liver Injury Despite Inhibiting Jun N-terminal Kinase and Caspase 3 Activation

Stabilization of Tumor Necrosis Factor α mRNA by Chronic Ethanol

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