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

Hashieh, Imad Abou; Mathieu, Sylvie; Besson, Florence; Gérolami, A

doi:10.1016/s0168-8278(96)80017-1

Cited by 16 publications

(14 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Incubation of WIF-B cells in the presence of 0.5 mM 4-MP alone had no observed morphological effects (data not shown). These results are in accordance with previous studies that noted impaired bile canaliculi formation in hepatocytes exposed to ethanol [34,35].…”

Section: Resultssupporting

confidence: 94%

“…Previous studies noted the loss of intercellular communication and impairment in bile canaliculi formation in hepatocytes treated with ethanol [34,35], so the mechanism(s) underlying these changes caused by ethanol may be similar between these two cell types. The morphological changes observed in the WIF-B cells after ethanol treatment may also involve altered cytoskeletal arrangement, leading not only to the observed morphological changes, but also altered functions.…”

Section: Discussionmentioning

confidence: 95%

See 1 more Smart Citation

WIF-B cells as a model for alcohol-induced hepatocyte injury

Schaffert

Todero

McVicker

et al. 2004

Biochemical Pharmacology

View full text Add to dashboard Cite

A potential in vitro model for studying the mechanisms of alcohol-induced hepatocyte injury is the WIF-B cell line. It has many hepatocyte-like features, including a differentiated, polarized phenotype resulting in formation of bile canaliculi. The aim of this study was to examine the effects of ethanol treatment on this cell line. WIF-B cells were cultured up to 96 h in the absence or presence of 25 mM ethanol and subsequently were analyzed for ethanol-induced physiological and morphological changes. Initial studies revealed WIF-B cells exhibited alcohol dehydrogenase (ADH) activity, expressed cytochrome P4502E1 (CYP2E1), and efficiently metabolized ethanol in culture. This cell line also produced the ethanol metabolite acetaldehyde and exhibited low K m aldehyde dehydrogenase (ALDH) activity, comparable to hepatocytes. Ethanol treatment of the WIF-B cells for 48 h led to significant increases in the lactate/pyruvate redox ratio and cellular triglyceride levels. Ethanol treatment also significantly altered WIF-B morphology, decreasing the number of bile canaliculi, increasing the number of cells exhibiting finger-like projections, and increasing cell diameter. The ethanol-induced changes occurring in this cell line were negated by addition of the ADH inhibitor, 4-methylpyrazole (4-MP), indicating the effects were due to ethanol metabolism. In summary, the WIF-B cell line metabolizes ethanol and exhibits many ethanol-induced changes similar to those found in hepatocytes. Because of these similarities, WIF-B cells appear to be a suitable model for studying ethanol-induced hepatocyte injury.

show abstract

Section: Resultssupporting

confidence: 94%

Section: Discussionmentioning

confidence: 95%

WIF-B cells as a model for alcohol-induced hepatocyte injury

Schaffert

Todero

McVicker

et al. 2004

Biochemical Pharmacology

View full text Add to dashboard Cite

show abstract

“…These data are consistent with studies from isolated hepatocytes demonstrating that acute alcohol treatment inhibits gap junction intercellular communication (Abou Hashieh et al . ). Moreover, the data suggest that the inhibitory actions of acute ethanol treatment on gap junctions are not altered by alcohol feeding and that chronic alcohol feeding by itself does not impede gap junction communication.…”

Section: Resultsmentioning

confidence: 97%

Chronic alcohol feeding potentiates hormone‐induced calcium signalling in hepatocytes

Bartlett

Antony

Agarwal

et al. 2017

The Journal of Physiology

View full text Add to dashboard Cite

Chronic alcohol consumption causes a spectrum of liver diseases, but the pathogenic mechanisms driving the onset and progression of disease are not clearly defined. We show that chronic alcohol feeding sensitizes rat hepatocytes to Ca -mobilizing hormones resulting in a leftward shift in the concentration-response relationship and the transition from oscillatory to more sustained and prolonged Ca increases. Our data demonstrate that alcohol-dependent adaptation in the Ca signalling pathway occurs at the level of hormone-induced inositol 1,4,5 trisphosphate (IP ) production and does not involve changes in the sensitivity of the IP receptor or size of internal Ca stores. We suggest that prolonged and aberrant hormone-evoked Ca increases may stimulate the production of mitochondrial reactive oxygen species and contribute to alcohol-induced hepatocyte injury. ABSTRACT: 'Adaptive' responses of the liver to chronic alcohol consumption may underlie the development of cell and tissue injury. Alcohol administration can perturb multiple signalling pathways including phosphoinositide-dependent cytosolic calcium ([Ca ] ) increases, which can adversely affect mitochondrial Ca levels, reactive oxygen species production and energy metabolism. Our data indicate that chronic alcohol feeding induces a leftward shift in the dose-response for Ca -mobilizing hormones resulting in more sustained and prolonged [Ca ] increases in both cultured hepatocytes and hepatocytes within the intact perfused liver. Ca increases were initiated at lower hormone concentrations, and intercellular calcium wave propagation rates were faster in alcoholics compared to controls. Acute alcohol treatment (25 mm) completely inhibited hormone-induced calcium increases in control livers, but not after chronic alcohol-feeding, suggesting desensitization to the inhibitory actions of ethanol. Hormone-induced inositol 1,4,5 trisphosphate (IP ) accumulation and phospholipase C (PLC) activity were significantly potentiated in hepatocytes from alcohol-fed rats compared to controls. Removal of extracellular calcium, or chelation of intracellular calcium did not normalize the differences in hormone-stimulated PLC activity, indicating calcium-dependent PLCs are not upregulated by alcohol. We propose that the liver 'adapts' to chronic alcohol exposure by increasing hormone-dependent IP formation, leading to aberrant calcium increases, which may contribute to hepatocyte injury.

show abstract

“…It is more likely that ethanol disturbs cell signaling and as a consequence disrupts normal function. There has been great interest in the signaling pathways that are disturbed by alcohol and several have been identified, including membrane receptor-mediated stimulation of second messengers, phospholipase C signaling, serine/threonine protein kinases, ion channels, cell adhesion, and gap junctional signaling (Hoek et al, 1988;Diamond and Gordon, 1997;Mochly-Rosen et al, 1988; Hoeket al, 1987;Slater et al, 1993;Constantinescu et al, 1999;Resnicoff et al, 1996;Miyakawa et al, 1997;Harris, 1999; Wilkemeyer et al, 2000;Abou Hashieh et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Alcohol and Adaptation to Mechanical Usage

Turner¹

2000

View full text Add to dashboard Cite

Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302, and to the Office of Management and Budget, Paperwork Reduction Project (0704-0188), Washington, DC 20503 AGENCY USE ONLY (Leave blank) REPORT DATE October 2000 REPORT TYPE AND DATES COVEREDAnnual (1 Sep 99 -31 Aug 00) TITLE AND SUBTITLE Alcohol and Adaptation to Mechanical Usage AUTHOR(S)Russell T. Turner, Ph.D. FUNDING NUMBERS DAMD17-98-1-8517 PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)Mayo Foundation Rochester, Minnesota 55905 E-MAIL: rolbiecki.lori@mayo.edu These studies are designed to determine whether ethanol antagonizes the ability of the skeleton to adapt to increased mechanical usage. Ethanol reversibly alters the biophysical properties of cell membranes.The overall hypothesis to be tested in adult rats is that these membrane changes disrupt essential cell signaling pathways for one or more cytokines, growth factors and polypeptide hormones that regulate bone modeling and remodeling.This report summarizes our progress from 01 September 1999 to 31 August 2000. During Year 2 of the award we have continued analysis of experiments performed in Year 1 related to Tasks 1-4 and 8.Additional experiments were performed to accomplish Task 8. Progress was also made on Tasks 6, 7, and 8.The new studies are directed toward determination of the effects of ethanol on: the skeletal readaptation to normal weight bearing following unloading (Task 6), skeletal adaptation to treadmill running (Task 7), PTH-induced increases in mRNA levels for bone matrix proteins (Task 8), and PTH-induced increases in osteoblast number and bone formation (Task 9). SUBJECT TERMS Neurotoxin NUMBER OF PAGES INTRODUCTIONChronic alcohol abuse is an important risk factor for osteoporosis. The ultimate goal of this research is to identify the cellular and molecular mechanisms responsible for mediating ethanol's dose-and time-dependent actions on bone turnover, mass, architecture, and strength. It is well established that ethanol reversibly alters the biophysical properties of cell membranes and in doing so disturbs normal membrane function. The proposed studies in young adult rats will test our working hypothesis that these membrane changes disrupt essential cell signaling pathways for one or more bone cells "coupling" factors and/or polypeptide hormones that regulate bone modeling and remodeling. These changes are postulated to lead to the bone loss associated with chronic alcohol abuse. If our hypothesis is correct, then ethanol antagonizes the ability of t...

show abstract

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

Cited by 16 publications

References 28 publications

WIF-B cells as a model for alcohol-induced hepatocyte injury

WIF-B cells as a model for alcohol-induced hepatocyte injury

Chronic alcohol feeding potentiates hormone‐induced calcium signalling in hepatocytes

Alcohol and Adaptation to Mechanical Usage

Contact Info

Product

Resources

About