Defective Translocation of PKCε in EtOH‐Induced Inhibition of Mg<sup>2+</sup> Accumulation in Rat Hepatocytes

Torres, Lisa M.; Konopnika, Bocena; Berti‐Mattera, Liliana N.; Liedtke, Carole M.; Romani, Andrea

doi:10.1111/j.1530-0277.2010.01252.x

Cited by 8 publications

(10 citation statements)

References 32 publications

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“…Cardiac cells from animals exposed to alcohol for 3 weeks require 10 days or so to restore their cellular Mg 2+ levels to pre-ethanol levels (Table 2). A similar time course has been observed in liver cells (Torres et al, 2009) and is related to the defective translocation of PKCε from cytoplasm to cell membrane (Torres et al, 2010). …”

Section: Discussionsupporting

confidence: 75%

“…Ethanol-treated rats were maintained for 3 weeks on a 6% (v/v) ethanol Lieber-DeCarli diet. Pair-fed control rats received an isocaloric liquid control diet (Dyets, Bethlehem, PA), as previously reported (Torres, Konopnika, Berti-Mattera, Liedtke, & Romani, 2010; Young et al, 2003). Age-matched, Purina Chow pellet-fed control rats were used for comparison.…”

Section: Methodsmentioning

confidence: 99%

“…The consequent increase in cytosolic free Mg 2+ promotes Mg 2+ extrusion through the Na + /Mg 2+ exchanger (Tessman & Romani, 1998). On the other hand, ethanol inhibits the Mg 2+ entry mechanism for more than 45 min after alcohol removal (Torres, Konopnika, Berti-Mattera, Liedtke, & Romani, 2010), de facto hampering the restoration of proper Mg 2+ homeostasis. Similar effects occur on prolonged bases in hepatocytes from animals exposed to alcohol in the diet for 3 weeks (Torres, Cefaratti, Berti-Mattera, & Romani, 2009; Young, Cefaratti, & Romani, 2003).…”

Section: Introductionmentioning

confidence: 99%

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Effect of acute and prolonged alcohol administration on Mg2+ homeostasis in cardiac cells

Romani¹

2015

Alcohol

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Alcoholic cardiomyopathy represents a major clinical complication in chronic alcoholics. Previous studies from our laboratory indicate that acute and chronic exposure of liver cells to ethanol results in a major loss of cellular Mg2+ as a result of alcohol oxidation. We investigated whether exposure to ethanol induces a similar Mg2+ loss in cardiac cells. The results indicate that chronic exposure to a 6% ethanol-containing diet depleted cardiac myocytes of >25% of their cellular Mg2+ content. Acute ethanol exposure, instead, induced a time- and dose-dependent manner of Mg2+ extrusion from perfused hearts and collagenase-dispersed cardiac ventricular myocytes. Pretreatment with chloromethiazole prevented ethanol-induced Mg2+ loss to a large extent, suggesting a role of ethanol oxidation via cyP4502E1 in the process. Magnesium extrusion across the sarcolemma occurred via the amiloride-inhibited Na+/Mg2+ exchanger. Taken together, our data indicate that Mg2+ extrusion also occurs in cardiac cells exposed to ethanol as a result of alcohol metabolism by cyP4502E1. The extrusion, which is mediated by the Na+/Mg2+ exchanger, only occurs at doses of ethanol ≥ 0.1%, and depends on ethanol-induced decline in cellular ATP. The significance of Mg2+ extrusion for the onset of alcoholic cardiomyopathy remains to be elucidated.

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Section: Discussionsupporting

confidence: 75%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of acute and prolonged alcohol administration on Mg2+ homeostasis in cardiac cells

Romani¹

2015

Alcohol

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“…The membranes were extensively washed with PBS, and the binding of primary antibodies against H6PD (Cell Signaling, Boston, MA) was visualized using peroxidase conjugated secondary antibodies and ECL western blotting detection reagents (Amersham). Protein expression was evaluated by densitometry using Scion Image program (NIH), as previously reported [22]. …”

Section: Methodsmentioning

confidence: 99%

Reduced cellular Mg2+ content enhances hexose 6-phosphate dehydrogenase activity and expression in HepG2 and HL-60 cells

Voma

Barfell

Croniger

et al. 2014

Archives of Biochemistry and Biophysics

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We have reported that Mg2+ dynamically regulates glucose 6-phosphate entry into the endoplasmic reticulum and its hydrolysis by the glucose 6-phosphatase in liver cells. In the present study, we report that by modulating glucose 6-phosphate entry into the endoplasmic reticulum of HepG2 cells, Mg2+ also regulates the oxidation of this substrate via hexose 6-phosphate dehydrogenase (H6PD). This regulatory effect is dynamic as glucose 6-phosphate entry and oxidation can be rapidly down-regulated by the addition of exogenous Mg2+. In addition, HepG2 cells growing in low Mg2+ show a marked increase in hexose 6-phosphate dehydrogenase mRNA and protein expression. Metabolically, these effects on hexose 6-phosphate dehydrogenase are important as this enzyme increases intra-reticular NADPH production, which favors fatty acid and cholesterol synthesis. Similar effects of Mg2+ were observed in HL-60 cells. These and previously published results suggest that in an hepatocyte culture model changes in cytoplasmic Mg2+ content regulates glucose 6-phosphate utilization via glucose 6 phosphatase and hexose-6 phosphate dehydrogenase in alternative to glycolysis and glycogen synthesis. This alternative regulation might be of relevance in the transition from fed to fasted state.

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“…The membranes were extensively washed with PBS, and the binding of primary antibodies against the catalytic subunit of G6Pase (Santa Cruz, Santa Cruz, CA) was visualized using peroxidase conjugated secondary antibodies and ECL western blotting detection reagents (Amersham). Protein expression was evaluated by densitometry using Scion Image program (NIH), as previously reported [25]. …”

Section: Methodsmentioning

confidence: 99%

Enhanced glucose 6-phosphatase activity in liver of rats exposed to Mg2+-deficient diet

Barfell

Crumbly

Romani

2011

Archives of Biochemistry and Biophysics

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Total hepatic Mg 2+ content decreases by >25% in animals maintained for two weeks on Mg 2+ deficient diet, and results in a >25% increase in glucose 6-phosphatase (G6Pase) activity in isolated liver microsomes in the absence of significant changed in enzyme expression. Incubation of Mg 2+ -deficient microsomes in the presence of 1mM external Mg 2+ returned G6Pase activity to levels measured in microsomes from animals on normal Mg 2+ diet. EDTA addition dynamically reversed the Mg 2+ effect. The effect of Mg 2+ or EDTA persisted in taurocholic acid permeabilized microsomes. An increase in G6Pase activity was also observed in liver microsomes from rats starved overnight, which presented a ~15% decrease in hepatic Mg 2+ content. In this model, G6Pase activity increased to a lesser extent than in Mg 2+ -deficient microsomes, but it could still be dynamically modulated by addition of Mg 2+ or EDTA. Our results indicate that 1) hepatic Mg 2+ content rapidly decreases following starvation or exposure to deficient diet, and 2) the loss of Mg 2+ stimulates G6P transport and hydrolysis as a possible compensatory mechanism to enhance intrahepatic glucose availability. The Mg 2+ effect appears to take place at the level of the substrate binding site of the G6Pase enzymatic complex or the surrounding phospholipid environment.

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Defective Translocation of PKCε in EtOH‐Induced Inhibition of Mg²⁺ Accumulation in Rat Hepatocytes

Cited by 8 publications

References 32 publications

Effect of acute and prolonged alcohol administration on Mg2+ homeostasis in cardiac cells

Effect of acute and prolonged alcohol administration on Mg2+ homeostasis in cardiac cells

Reduced cellular Mg2+ content enhances hexose 6-phosphate dehydrogenase activity and expression in HepG2 and HL-60 cells

Enhanced glucose 6-phosphatase activity in liver of rats exposed to Mg2+-deficient diet

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Defective Translocation of PKCε in EtOH‐Induced Inhibition of Mg2+ Accumulation in Rat Hepatocytes

Cited by 8 publications

References 32 publications

Effect of acute and prolonged alcohol administration on Mg2+ homeostasis in cardiac cells

Effect of acute and prolonged alcohol administration on Mg2+ homeostasis in cardiac cells

Reduced cellular Mg2+ content enhances hexose 6-phosphate dehydrogenase activity and expression in HepG2 and HL-60 cells

Enhanced glucose 6-phosphatase activity in liver of rats exposed to Mg2+-deficient diet

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Defective Translocation of PKCε in EtOH‐Induced Inhibition of Mg²⁺ Accumulation in Rat Hepatocytes