Inhibition of gap junction intercellular communications of cultured rat hepatocytes by ethanol: role of ethanol metabolism. 1996

I Abou Hashieh, and S Mathieu, and F Besson, and A Gerolami
Inserm U260, Faculté de Médecine, Marseille, France.

OBJECTIVE In a previous study, we reported that in cultured rat hepatocytes, ethanol inhibits intercellular communication which is known to play a central role in the regulation of cell growth and differentiation. This work was designed to find out if ethanol exerts a direct action on cell membranes, comparable to other long-chain (C6-C9) alcohols, or an indirect action. METHODS Intercellular communication was measured on short-term cultured rat hepatocytes by the fluorescent Lucifer-Yellow CH transfer method. Intracellular pH was measured by spectrofluorimetry and membrane expression of connexin 32 by indirect immunofluorescence. RESULTS Under our conditions, ethanol (20 mM) inhibited intercellular communication of hepatocytes to the same extent as did octanol and 1 mM. Immunofluorescence semi-quantitative studies of connexin 32 suggested that the observed inhibition was not related to a decrease in the number of gap junction plaques. In contrast with those of octanol, the inhibitory effects of ethanol appeared to be indirect because the inhibition of ethanol metabolism by 4-methyl pyrazole abolished its effects on intercellular communication, while 4-methyl pyrazole did not influence the effects of octanol. Acetaldehyde, the main metabolite of ethanol was without effect on gap junctions. CONCLUSIONS This suggests that the inhibition of intercellular communication induced by ethanol may be included among the consequences of intermediary cell metabolism disturbances indirectly due to ethanol oxidation. This may be one of the mechanisms by which ethanol metabolism exerts a hepatotoxic possibly carcinogenic action.

UI MeSH Term Description Entries
D007546 Isoquinolines A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D008854 Microscopy, Electron Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen. Electron Microscopy
D011720 Pyrazoles Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.
D002450 Cell Communication Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP. Cell Interaction,Cell-to-Cell Interaction,Cell Communications,Cell Interactions,Cell to Cell Interaction,Cell-to-Cell Interactions,Communication, Cell,Communications, Cell,Interaction, Cell,Interaction, Cell-to-Cell,Interactions, Cell,Interactions, Cell-to-Cell
D002462 Cell Membrane The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells. Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D002492 Central Nervous System Depressants A very loosely defined group of drugs that tend to reduce the activity of the central nervous system. The major groups included here are ethyl alcohol, anesthetics, hypnotics and sedatives, narcotics, and tranquilizing agents (antipsychotics and antianxiety agents). CNS Depressants,Depressants, CNS
D005456 Fluorescent Dyes Chemicals that emit light after excitation by light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. Flourescent Agent,Fluorescent Dye,Fluorescent Probe,Fluorescent Probes,Fluorochrome,Fluorochromes,Fluorogenic Substrates,Fluorescence Agents,Fluorescent Agents,Fluorogenic Substrate,Agents, Fluorescence,Agents, Fluorescent,Dyes, Fluorescent,Probes, Fluorescent,Substrates, Fluorogenic

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