The Role of Protein Kinase C in Cellular Tolerance to Ethanol

Coe, Imogen R.; Yao, Lina; Diamond, Ivan; Gordon, Adrienne S.

doi:10.1074/jbc.271.46.29468

Cited by 70 publications

(51 citation statements)

References 27 publications

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“…Ethanol alters the amount, activity, and subcellular distribution of PKC. Increased amounts of ␣-, ␦-, and ⑀-PKC in NG108 -15 cells (8) and of ␦-and ⑀-PKC in PC12 cells (9) are found after chronic ethanol exposure, and there is increased activity of PKC in NG108 -15 and PC12 cells (9). PKC activity is also increased in human platelets (10), lymphocytes (11), and epidermal keratinocytes (12) after acute ethanol exposure.…”

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confidence: 99%

Ethanol Alters the Subcellular Localization of δ- and ε Protein Kinase C in NG108–15 Cells

Gordon

Yao

et al. 1997

Mol Pharmacol

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SUMMARYProtein kinase C (PKC) has been shown to regulate the ethanol sensitivity of membrane-bound receptors and transporters, but little is known about the molecular mechanisms underlying this regulation. PKC is a family of isozymes that translocate to new intracellular sites on activation. Here we present immunochemical data showing that ethanol causes translocation of ␦-and ⑀-PKC to new intracellular sites. Ethanol causes translocation of ␦-PKC from the Golgi to the perinucleus; this translocation is similar to that induced by activation of PKC with phorbol esters.In contrast, ⑀-PKC translocation caused by ethanol is different from that induced by phorbol esters; ethanol causes translocation of ⑀-PKC from the perinucleus to the cytoplasm, whereas phorbol ester activation causes translocation of ⑀-PKC to the nucleus. Because the substrate specificity of these kinases is determined by their site of localization, ethanol-induced translocation of ␦-and ⑀-PKC to new intracellular sites may explain some of the pleiotropic effects of ethanol on cellular functions.PKC, a family of isozymes that mediates multiple cellular functions, has been shown to regulate the effects of ethanol on receptors (1-6) and membrane-bound transporters (7), but the mechanism underlying this regulation is unknown. Ethanol alters the amount, activity, and subcellular distribution of PKC. Increased amounts of ␣-, ␦-, and ⑀-PKC in NG108 -15 cells (8) and of ␦-and ⑀-PKC in PC12 cells (9) are found after chronic ethanol exposure, and there is increased activity of PKC in NG108 -15 and PC12 cells (9). PKC activity is also increased in human platelets (10), lymphocytes (11), and epidermal keratinocytes (12) after acute ethanol exposure. Moreover, ethanol causes translocation of PKC activity from cytosolic to membrane fractions in astroglial cells (13), human lymphocytes (11), and epidermal keratinocytes (12).On activation, each PKC isozyme translocates from a specific intracellular site to another (14). Recent evidence suggests that the specificity of substrate phosphorylation of each isozyme is determined by its localization (14). Ethanol-induced activation and translocation of specific PKC isozymes to new intracellular sites could therefore account for many of the pleiotropic effects of ethanol on cell functions. To test this hypothesis, we carried out studies on the localization of ␦-and ⑀-PKC in NG108 -15 neuroblastoma ϫ glioma hybrid cells. We report here that ethanol causes translocation of ␦-and ⑀-PKC to new intracellular sites in these cells. Materials and MethodsCell culture. NG108-15 neuroblastoma ϫ glioma hybrid cells were seeded in single-chamber slides in defined media consisting of Dulbecco's modified Eagle's medium/Ham's F-12 medium (3:1); 0.1 mM hypoxanthine; 1.0 M aminopterin; 12 mM thymidine; 25 mM HEPES, pH 7.4; trace elements (0.5 nM MnCl 2 , 0.5 nM [NH 4 ] 6 Mo 7 O 24 , 0.25 nM SnCl 4 , 25 nM Na 3 VO 4 , 5 nM CdSO 4 , 0.25 nM NiSO 4 , 15 nM H 2 SeO 3 , 25 nM Na 2 SiO 3 ); bovine insulin (5 g/ml); human transferrin (50 g/ml);...

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confidence: 99%

Ethanol Alters the Subcellular Localization of δ- and ε Protein Kinase C in NG108–15 Cells

Gordon

Yao

et al. 1997

Mol Pharmacol

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“…However, we did not test if PKC delta distribution was altered in these animals. Other reports demonstrate that the alcohol-induced changes in PKC are also found in neuronal cells (Coe et al, 1996;Messing et al, 1991). In PC12 cells, adaptation to alcohol involves increased expression of both PKC delta and epsilon (Messing et al, 1991).…”

Section: Discussionmentioning

confidence: 98%

“…This concentration of ethanol is within the range (50-200 mM) that has previously been shown to alter PKC in tissue culture (Coe et al, 1996;Messing et al, 1991). For the experiments, only low passage cells (<15) were used.…”

Section: H9c2 Cell Culturementioning

confidence: 90%

“…Several laboratories, including this laboratory, have reported that alcohol exposure alters PKC expression and activity in different cell lines and tissues (Coe et al, 1996;Messing et al, 1991;Miyamae et al, 1998;Solem et al, 2000). Therefore, we examined if chronic-alcohol exposure of H9c2 embryonic heart cells alters PKC alpha, delta, and epsilon expression and activity.…”

Section: Discussionmentioning

confidence: 99%

“…Ethanol also increases the abundance of L-type channels in these cells by at least two mechanisms; one involving increases in mRNA encoding the α 1C subunit, and the other involving a posttranscriptional mechanism that requires PKC delta (Walter et al, 2000). In NG108 cells, ethanol increases the amounts of PKC alpha, delta, and epsilon in these cells, and it is believed that the sensitivity of adenosine transport is due to a balance of PKA and protein phosphatase activities, which is regulated by PKC (Coe et al, 1996). Therefore, several different types of PKC are modulated by alcohol in the heart and in other tissues, and this effect may lead to cellular changes that are associated with PKC activity.…”

Section: Discussionmentioning

confidence: 99%

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Transplantation of fecal microbiota from patients with alcoholism induces anxiety/depression behaviors and decreases brain mGluR1/PKC ε levels in mouse

Zhao

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Recent studies have revealed that the gut microbiota participates in the psychiatric behavior changes in disorders associated with alcohol. But it still remains unknown whether alcoholism is involved in changes in gut microbiota and its underlying mechanism is also not clear. Here, we tested the gut microbiota of patients with alcoholism and conducted fecal microbiota transplantation (FMT) from patients with alcoholism to C57BL/6J mice whose gut microbiota had been sharply suppressed with antibiotics (ABX). Then we evaluated their alcohol preference degree, anxiety, and depression-like behaviors and social interaction behaviors, together with molecular changes in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc). Our data indicated that the gut microbiota of patients with alcoholism was drastically different from those of the healthy adults. The abundance of p_Firmicutes was significantly increased whereas p_Bacteroidetes was decreased. Compared to mice transplanted with fecal microbiota from healthy male adults, the mice accepting fecal microbiota from patients with alcoholism showed (a) anxiety-like and depression-like behaviors, (b) decreased social interaction behaviors, (c) spontaneous alcohol preference, and (d) decreased brain-derived neurotrophic factor (BDNF), alpha 1 subunit of GABA type A receptor (α1GABA A R) in mPFC and decreased metabotropic glutamate receptors 1 (mGluR1), protein kinase C (PKC) ε in NAc. Overall, our results suggest that fecal microbiota from patients with

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The Role of Protein Kinase C in Cellular Tolerance to Ethanol

Cited by 70 publications

References 27 publications

Ethanol Alters the Subcellular Localization of δ- and ε Protein Kinase C in NG108–15 Cells

Ethanol Alters the Subcellular Localization of δ- and ε Protein Kinase C in NG108–15 Cells

Chronic-alcohol exposure alters IGF1 signaling in H9c2 cells via changes in PKC delta

Transplantation of fecal microbiota from patients with alcoholism induces anxiety/depression behaviors and decreases brain mGluR1/PKC ε levels in mouse

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