Activation of pertussis toxin-sensitive G-proteins in membranes of SH-SY5Y human neuroblastoma cells and bovine transducin by ethanol

Klinker, Jan F.; Lichtenberg-Kraag, Birgit; Damm, Henning; Rommelspacher, Hans

doi:10.1016/0304-3940(96)12816-0

Cited by 16 publications

(5 citation statements)

References 8 publications

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“…Ethanol activates a number of enzymes via a G i -protein-dependent mechanism [36,43,44], although the nature of the effect of ethanol on G-protein function is not well understood. It is believed that ethanol can influence both the function and the gene expression of G-proteins [45,46]. We found that a brief (30 min) exposure of hepatocytes to ethanol prolonged the agonist activation of p42\44 MAPK (J. Chen, E. J. Ishac, P. Dent, G. Kunos and B. Gao, unpublished work), which suggests that ethanol may directly affect G-protein function in primary hepatocytes.…”

Section: Discussionmentioning

confidence: 57%

Effects of ethanol on mitogen-activated protein kinase and stress-activated protein kinase cascades in normal and regenerating liver

Chen

Ishac

Dent

et al. 1998

Biochemical Journal

105

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To understand the mechanisms by which ethanol inhibits hepatocyte proliferation, we studied the effects of ethanol on p42/44 mitogen-activated protein kinase (MAPK), p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK) in normal and regenerating rat liver. Treatment of rat hepatocytes with 100 mM ethanol in vitro for 16 h prolonged the activation of p42/44 MAPK and p38 MAPK induced by various agonists. Such treatment also increased basal JNK activity, but did not potentiate or prolong agonist-induced JNK activation. Ethanol potentiation of the activation of p42/44 MAPK was abolished by pertussis toxin. In contrast, chronic ethanol consumption in vivo inhibited the activation of p42/44 MAPK, p38 MAPK and JNK induced either by partial hepatectomy or by various agonists. However, both acute and chronic ethanol inhibited hepatocyte proliferation induced by insulin and epidermal growth factor. A selective inhibitor of p42/44 MAPK partially prevented the inhibition of hepatocyte proliferation caused by acute, but not by chronic, ethanol exposure, whereas a selective inhibitor of p38 MAPK further inhibited hepatocyte proliferation under both conditions. These data suggest that acute and chronic ethanol inhibit hepatocyte proliferation by different mechanisms. The effect of acute ethanol may be related to the prolongation of p42/44 MAPK activation, whereas inhibition of hepatocyte proliferation by chronic ethanol may be due to inhibition of p38 MAPK activation.

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Section: Discussionmentioning

confidence: 57%

Effects of ethanol on mitogen-activated protein kinase and stress-activated protein kinase cascades in normal and regenerating liver

Chen

Ishac

Dent

et al. 1998

Biochemical Journal

105

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“…This suggests that one candidate for ethanol's target may be a G‐protein–coupled receptor (GPCR). Interactions between ethanol and GPRCs are well documented (Klinker et al, 1996; Lewohl et al, 1999; Rubin and Hoek, 1988; Yao et al, 2002, 2003). As a prelude to identify the protein target of ethanol that mediates this signaling cascade, we have established the alcohol‐binding criteria that any such candidate must meet.…”

Section: Discussionmentioning

confidence: 99%

Structural Constraints for Alcohol‐Stimulated Ca²⁺ Release in Neural Crest, and Dual Agonist/Antagonist Properties of n‐Octanol

Garic-Stankovic

Hernandez

Flentke

et al. 2006

Alcoholism Clin & Exp Res

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The selective, saturable effect of n-alcohols upon Ca2+ mobilization in neural crest is consistent with a hypothesis that ethanol stimulates these signals through specific interaction with one or more alcohol-binding sites on a target protein. Octanol may overcome structural constraints imposed upon C6 and C7 in interacting with this protein target; alternatively, it may interact through a unique binding site.

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“…However, in both systems, significant peptide-induced increases in GTPase activity were observed. Nonreceptor mediated GTPase activation has been documented with mastoparan, ethanol, and shear stress (59,(97)(98)(99). The discovery that our A␤ GTPase activities may be membranemediated is consistent with a number of other previous findings, which imply the importance of A␤-membrane interactions to neurotoxicity.…”

Section: Discussionmentioning

confidence: 99%

The Role of G Protein Activation in the Toxicity of Amyloidogenic Aβ-(1–40), Aβ-(25–35), and Bovine Calcitonin

Rymer

Good

2001

Journal of Biological Chemistry

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More than 16 different proteins have been identified as amyloid in clinical diseases; among these, ␤-amyloid (A␤) of Alzheimer's disease is the best characterized. In the present study, we performed experiments with A␤ and calcitonin, another amyloid-forming peptide, to examine the role of G protein activation in amyloid toxicity. We demonstrated that the peptides, when prepared under conditions that promoted ␤-sheet and amyloid fibril (or protofibril) formation, increased high affinity GTPase activity, but the nonamyloidogenic peptides had no discernible effects on GTP hydrolysis. These increases in GTPase activity were correlated to toxicity. In addition, G protein inhibitors significantly reduced the toxic effects of the amyloidogenic A␤ and calcitonin peptides. Our results further indicated that the amyloidogenic peptides significantly increased GTPase activity of purified G␣ o and G␣ i subunits and that the effect was not receptor-mediated. Collectively, these results imply that the amyloidogenic structure, regardless of the actual peptide or protein sequence, may be sufficient to cause toxicity and that toxicity is mediated, at least partially, through G protein activation. Our abilities to manipulate G protein activity may lead to novel treatments for Alzheimer's disease and the other amyloidoses.

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Activation of pertussis toxin-sensitive G-proteins in membranes of SH-SY5Y human neuroblastoma cells and bovine transducin by ethanol

Cited by 16 publications

References 8 publications

Effects of ethanol on mitogen-activated protein kinase and stress-activated protein kinase cascades in normal and regenerating liver

Effects of ethanol on mitogen-activated protein kinase and stress-activated protein kinase cascades in normal and regenerating liver

Structural Constraints for Alcohol‐Stimulated Ca²⁺ Release in Neural Crest, and Dual Agonist/Antagonist Properties of n‐Octanol

The Role of G Protein Activation in the Toxicity of Amyloidogenic Aβ-(1–40), Aβ-(25–35), and Bovine Calcitonin

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Activation of pertussis toxin-sensitive G-proteins in membranes of SH-SY5Y human neuroblastoma cells and bovine transducin by ethanol

Cited by 16 publications

References 8 publications

Effects of ethanol on mitogen-activated protein kinase and stress-activated protein kinase cascades in normal and regenerating liver

Effects of ethanol on mitogen-activated protein kinase and stress-activated protein kinase cascades in normal and regenerating liver

Structural Constraints for Alcohol‐Stimulated Ca2+ Release in Neural Crest, and Dual Agonist/Antagonist Properties of n‐Octanol

The Role of G Protein Activation in the Toxicity of Amyloidogenic Aβ-(1–40), Aβ-(25–35), and Bovine Calcitonin

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Product

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Structural Constraints for Alcohol‐Stimulated Ca²⁺ Release in Neural Crest, and Dual Agonist/Antagonist Properties of n‐Octanol