Chronic EtOH administration alters liver Mg2+homeostasis

2003 ◽  
Vol 284 (1) ◽  
pp. G57-G67 ◽  
Author(s):  
Andrew Young ◽  
Christie Cefaratti ◽  
Andrea Romani
Keyword(s):  
Adrenergic Receptor ◽  
Prolonged Exposure ◽  
Liver Cells ◽  
Chronic Alcohol ◽  
Atp Content ◽  
Chronic Alcohol Consumption ◽  
Kinase C ◽  
And Control ◽  
Total Tissue ◽  
Stimulation Of

Ethanol (EtOH) administration to rats for 4 wk markedly decreased Mg2+ content in several tissues, including liver. Total cellular Mg2+ accounted for 26.8 ± 2.4 vs. 36.0 ± 1.4 nmol Mg2+/mg protein in hepatocytes from EtOH-fed and control rats, respectively, and paralleled a 13% decrease in cellular ATP content. Stimulation of α1- or β-adrenergic receptor or acute EtOH administration did not elicit an extrusion of Mg2+ from liver cells of EtOH-fed rats while releasing 5% of total tissue Mg2+ content from hepatocytes of control rats. Despite the 25% decrease in Mg2+ content, hepatocytes from EtOH-fed rats did not accumulate Mg2+following stimulation of protein kinase C signaling pathway, whereas control hepatocytes accumulated ∼2 nmol Mg2+ · mg protein−1 · 4 min−1. Together, these data indicate that Mg2+ homeostasis and transport are markedly impaired in liver cells after prolonged exposure to alcohol. The inability of liver cells, and possibly other tissues, to accumulate Mg2+ can help explain the reduction in tissue Mg2+ content following chronic alcohol consumption.

scholarly journals The characteristics and site of inhibition of gluconeogenesis in rat liver cells by bacterial endotoxin. Stimulation of phosphofructokinase-1

1987 ◽  
Vol 242 (3) ◽  
pp. 721-728 ◽  
Author(s):  
R G Knowles ◽  
J P McCabe ◽  
S J Beevers ◽  
C I Pogson
Keyword(s):  
Enzyme Activities ◽  
Pyruvate Carboxylase ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Liver Cells ◽  
Atp Content ◽  
Rat Liver Cells ◽  
Endogenous Substrates ◽  
And Control ◽  
Control Coefficients ◽  
Stimulation Of

The characteristics and site of inhibition of gluconeogenesis by endotoxin were investigated in liver cells isolated from control and endotoxin-treated rats. Endotoxin treatment was associated with inhibition (40-50%) of gluconeogenesis from lactate plus pyruvate over a range of concentrations of substrate and of oleate and with or without glucose or glucagon. Similar inhibition was observed with asparagine, proline, glutamine, alanine and a substrate mixture, but not with glycerol, glyceraldehyde, dihydroxyacetone or endogenous substrates. There was no change in cellular ATP content or in the rates of ketogenesis or ureogenesis from asparagine, proline or glutamine. Other effects on isotopic fluxes, metabolite contents, enzyme activities and control coefficients were consistent with the suggestion that the effects of endotoxin on gluconeogenesis are exerted at the level of phosphofructokinase-1, and not at phosphoenolpyruvate carboxykinase, pyruvate kinase, pyruvate carboxylase or glucokinase.

scholarly journals Streptozotocin-induced diabetes impairs Mg2+ homeostasis and uptake in rat liver cells

2004 ◽  
Vol 286 (2) ◽  
pp. E184-E193 ◽  
Author(s):  
Theresa E. Fagan ◽  
Christie Cefaratti ◽  
Andrea Romani
Keyword(s):  
Liver Cells ◽  
Atp Content ◽  
Sprague Dawley ◽  
Uptake Mechanism ◽  
Diabetes Onset ◽  
Kinase C ◽  
Sprague Dawley Rats ◽  
Rat Liver Cells ◽  
Streptozotocin Induced Diabetes ◽  
Stimulation Of

Male Sprague-Dawley rats rendered diabetic by streptozotocin injection presented 10 and 20% decreases in total hepatic Mg2+ content at 4 and 8 wk, respectively, following diabetes onset. This decrease was associated with a parallel decrease in K+ and ATP content and an increase in Na+ level. In diabetic liver cells, the Mg2+ extrusion elicited by α1-adrenoceptor stimulation was markedly reduced compared with nondiabetic livers, whereas that induced by β-adrenoceptor stimulation was unaffected. In addition, diabetic hepatocytes did not accumulate Mg2+ following stimulation of protein kinase C pathway by vasopressin, diacylglycerol analogs, or phorbol 12-myristate 13-acetate derivates despite the reduced basal content in cellular Mg2+. Experiments performed in purified plasma membrane from diabetic livers located the defect at the level of the bidirectional Na+/Mg2+ exchanger operating in the basolateral domain of the hepatocyte cell membrane, which could extrude but not accumulate Mg2+ in exchange for Na+. The impairment of Mg2+ uptake mechanism, in addition to the decrease in cellular ATP level, can contribute to explaining the decrease in liver Mg2+ content observed under diabetic conditions.

Epinephrine-mediated protein kinase C and Rap1b activation requires the co-stimulation of Gz-, Gq-, and Gi-coupled receptors

2011 ◽  
Vol 105 (03) ◽  
pp. 479-486 ◽  
Author(s):  
Ilaria Canobbio ◽  
Silvia Catricalà ◽  
Cesare Balduini ◽  
Paolo Lova ◽  
Gianni Francesco Guidetti ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Adrenergic Receptor ◽  
Dense Granules ◽  
Kinase C ◽  
Adrenergic Antagonist ◽  
Adp Receptors ◽  
Strong Stimulation ◽  
Dose Dependent ◽  
Stimulation Of

SummaryWe have recently shown that ADP-induced activation of protein kinase C (PKC) requires the co-stimulation of both P2Y1 and P2Y12 receptors. In this work, we show that inhibition of ADP-mediated phosphorylation of pleckstrin, the main PKC substrate, caused by antagonists of the P2Y12 receptor can be reversed by stimulation of the α2-adrenergic receptor by epinephrine. However, we also observed that addition of epinephrine alone caused a marked phosphorylation of pleckstrin. This effect occurred in the absence of Gq stimulation, as it was not associated to intracellular Ca2+ release. Epinephrine-induced pleckstrin phosphorylation was time- and dose-dependent, and was inhibited by the α2-adrenergic antagonist yohimbin. Phosphorylation of pleckstrin did not occur when platelet stimulation with epinephrine was performed in the presence of the ADP scavenger apyrase, and was suppressed by antagonists of both P2Y1 and P2Y12 ADP receptors. Importantly, no release of dense granules was measured in epinephrine-treated platelets. Addition of epinephrine to platelets was also able to stimulate Rap1b activation. Similarly to pleckstrin phosphorylation, however, this effect was prevented in the presence of apyrase or upon pharmacologic blockade of either P2Y1 or P2Y12 receptors. These results indicate that sub-threshold amounts of ADP in the medium are essential to allow epinephrine stimulation of α2-adrenergic receptor to elicit platelet responses, and reveal a novel synergism among strong stimulation of Gz and sub-threshold stimulation of both Gq and Gi, able to dissociate PKC activation from intracellular Ca2+ mobilisation.

Activation of Na+- and Ca2+-dependent Mg2+ extrusion by α1- and β-adrenergic agonists in rat liver cells

2000 ◽  
Vol 279 (5) ◽  
pp. G943-G950 ◽  
Author(s):  
Theresa E. Fagan ◽  
Andrea Romani
Keyword(s):  
Adrenergic Receptor ◽  
Liver Cells ◽  
Adrenergic Agonists ◽  
Experimental Conditions ◽  
Rat Liver Cells ◽  
Rat Livers ◽  
Cellular Ca ◽  
Adrenergic Receptor Agonist ◽  
Dependent Mechanism ◽  
Stimulation Of

The administration of selective α1 (phenylephrine)-, β (isoproterenol)-, or mixed (epinephrine) adrenergic agonists induces a marked Mg2+extrusion from perfused rat livers. In the absence of extracellular Ca2+, phenylephrine does not induce a detectable Mg2+ extrusion, isoproterenol-induced Mg2+mobilization is unaffected, and epinephrine induces a net Mg2+ extrusion that is lower than in the presence of extracellular Ca2+ and quantitatively similar to that elicited by isoproterenol. In the absence of extracellular Na+, no Mg2+ is extruded from the liver irrespective of the agonist used. Similar results are observed in perfused livers stimulated by glucagon or 8-chloroadenosine 3′,5′-cyclic monophosphate. In the absence of extracellular Na+ or Ca2+, adrenergic-induced glucose extrusion from the liver is also markedly decreased. Together, these results indicate that liver cells extrude Mg2+ primarily via a Na+-dependent mechanism. This extrusion pathway can be activated by the increase in cellular cAMP that follows the stimulation by glucagon or a specific β-adrenergic receptor agonist or, alternatively, by the changes in cellular Ca2+ induced by the stimulation of the α1-adrenoceptor. In addition, the stimulation of the α1-adrenoceptor appears to activate an auxiliary Ca2+-dependent Mg2+extrusion pathway. Finally, our data suggest that experimental conditions that affect Mg2+ mobilization also interfere with glucose extrusion from liver cells.

Chronic alcohol feeding impairs hepatic translation initiation by modulating eIF2 and eIF4E

1999 ◽  
Vol 277 (5) ◽  
pp. E805-E814 ◽  
Author(s):  
Charles H. Lang ◽  
Duanqing Wu ◽  
Robert A. Frost ◽  
Leonard S. Jefferson ◽  
Thomas C. Vary ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Translation Initiation ◽  
Plasma Concentrations ◽  
Translational Efficiency ◽  
Chronic Alcohol ◽  
Cellular Mechanisms ◽  
Chronic Alcohol Consumption ◽  
Initiation Factors ◽  
Eif2α Phosphorylation ◽  
And Control

The present study examined potential cellular mechanisms responsible for the inhibition of protein synthesis in liver after chronic alcohol consumption. Rats were maintained on an alcohol-containing diet for 14 wk; control animals were fed isocalorically. Hepatic ATP content was not different in alcohol-fed and control animals. No alcohol-induced reduction in total hepatic RNA content (an estimate of ribosomal RNA) was detected, suggesting that alcohol decreased translational efficiency. Alcohol feeding increased the proportion of 40S and 60S ribosomal subunits in the nonpolysome-associated fraction by 30%. To identify mechanisms responsible for the impairment in initiation, several eukaryotic initiation factors (eIF) were analyzed. Alcohol feeding decreased hepatic eIF2B activity by 36%. This reduction was associated with a 20% decrease in eIF2Bε content and a 90% increase in eIF2α phosphorylation. Alcohol also dramatically influenced the distribution of eIF4E. Compared with pair-fed control values, alcohol feeding increased the amount of eIF4E present in the inactive 4E-binding protein 1 (4E-BP1) ⋅ eIF4E complex by 80% and decreased binding of eIF4G to eIF4E by 70%. However, the phosphorylation status of 4E-BP1 and eIF4E was not altered by alcohol. Although the plasma concentrations of threonine, proline, and citrulline were mildly decreased, the circulating amount of total amino acids was not altered by alcohol feeding. In summary, these data suggest that chronic alcohol consumption impairs translation initiation in liver by altering eIF2B activity as well as eIF4F function via changes in eIF4E availability.

scholarly journals Effects of ethanol on offspring of C57BL/6J mice alcoholized during gestation

1999 ◽  
Vol 14 (3) ◽  
pp. 100-107
Author(s):  
Hermann Grinfeld ◽  
Saul Goldenberg ◽  
Conceição Aparecida de Mattos Segre ◽  
Gerson Chadi
Keyword(s):  
Tap Water ◽  
The Body ◽  
Control Group ◽  
Chronic Alcohol ◽  
Equivalent Weight ◽  
Chronic Alcohol Consumption ◽  
Gestational Period ◽  
Pregnant Mice ◽  
Ad Libitum ◽  
And Control

The effects of chronic alcohol consumption during pregnancy were analysed in the gestation and offspring of alcoholized mice. Female C57BL/6J mice were placed overnight with stud males and the presence of a sperm plug in the next morning indicated the onset of gestation. Pregnant mice were distributed in two weight-matched groups. In the alcoholized group, the mice received a high protein liquid diet ad libitum containing 27.5% of ethanol-derived calories (5.28% v/v) from gestation day 5 to 19. The control group received the same volume of diet containing isocaloric amounts of maltose-dextrin substituted for ethanol. After postnatal day zero, the dams received food pellets and tap water ad libitum. On postnatal day 6 the pups were counted and weighed at variable intervals up to the 60th day of life. The majority of the pregnant dams that have received ethanol completed the gestational period, and the chronic consumption of alcohol did not interfere with the number of dams that gave birth. The alcoholized and control dams gained an equivalent weight and consumed an equivalent volume of diet throughout the gestation. The number of pups from alcohol diet dams was 46,26% smaller compared with the control group. There were less male than female pups in the offspring of alcoholized mice. Teratogeny like gastroschisis and limb malformation were present in the offspring of alcoholized dams. The body weight of the offspring of alcoholized mice increased from the 18th to the 36th postnatal day.

scholarly journals 3,5,3′-Tri-iodo-l-thyronine acutely regulates a protein kinase C-sensitive, Ca2+-independent, branch of the hepatic α1-adrenoreceptor signalling pathway

1998 ◽  
Vol 331 (1) ◽  
pp. 89-97 ◽  
Author(s):  
Francisco J. DAZA ◽  
Roberto PARRILLA ◽  
Angeles MARTÍN-REQUERO
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Hepatic Metabolism ◽  
Liver Cells ◽  
Signalling Pathway ◽  
Perfused Liver ◽  
Kinase C ◽  
Isolated Liver Cells ◽  
Isolated Liver ◽  
Stimulation Of

This work aimed to investigate the acute effect of the thyroid hormone 3,5,3´-tri-iodo-l-thyronine (T3) in regulating the hepatic metabolism either directly or by controlling the responsiveness to Ca2+-mobilizing agonists. We did not detect any acute metabolic effect of T3 either in perfused liver or in isolated liver cells. However, T3 exerted a powerful inhibitory effect on the α1-adrenoreceptor-mediated responses. The promptness of this T3 effect rules out that it was the result of rate changes in gene(s) transcription. T3 inhibited the α1-adrenoreceptor-mediated sustained stimulation of respiration and release of Ca2+ and H+, but not the glycogenolytic or gluconeogenic responses, in perfused liver. In isolated liver cells, T3 enhanced the α1-agonist-induced increase in cytosolic free Ca2+ and impeded the intracellular alkalinization. Since T3 also prevented the α1-adrenoreceptor-mediated activation of protein kinase C, its effects on pH seem to be the result of a lack of activation of the Na+/H+ exchanger. The failure of T3 to prevent the α1-adrenergic stimulation of gluconeogenesis despite the inhibition of protein kinase C activation indicates that the elevation of cytosolic free Ca2+ is a sufficient signal to elicit that response. T3 also impaired some of the angiotensin-II-mediated responses, but did not alter the effects of PMA on hepatic metabolism, indicating, therefore, that some postreceptor event is the target for T3 actions. The differential effect of T3 in enhancing the α1-adrenoreceptor-mediated increase in cytosolic free Ca2+ and preventing the activation of protein kinase C, provides a unique tool for further investigating the role of each branch of the signalling pathway in controlling the hepatic functions. Moreover, the low effective concentrations of T3 (⩽ 10 nM) in perturbing the α1-adrenoreceptor-mediated response suggests its physiological significance.

Effects of Hypophysectomy on the Fine Structure of Rat Liver Cells

1967 ◽  
Vol 25 ◽  
pp. 156-157
Author(s):  
Robert R. Cardell
Keyword(s):  
Electron Microscopy ◽  
Fine Structure ◽  
Rat Liver ◽  
Liver Cell ◽  
Anterior Pituitary ◽  
Liver Cells ◽  
Biochemical Studies ◽  
Liver Functions ◽  
Rat Liver Cells ◽  
And Control

Hypophysectomy of the rat renders this animal deficient in the hormones of the anterior pituitary gland, thus causing many primary and secondary hormonal effects on basic liver functions. Biochemical studies of these alterations in the rat liver cell are quite extensive; however, relatively few morphological observations on such cells have been recorded. Because the available biochemical information was derived mostly from disrupted and fractionated liver cells, it seemed desirable to examine the problem with the techniques of electron microscopy in order to see what changes are apparent in the intact liver cell after hypophysectomy. Accordingly, liver cells from rats which had been hypophysectomized 5-120 days before sacrifice were studied. Sham-operated rats served as controls and both hypophysectomized and control rats were fasted 15 hours before sacrifice.

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