Ethanol specifically alters the synthesis, acylation and transbilayer movement of aminophospholipids in rat-liver microsomes

Carrasco, Marı́a P.; Jiménez-López, José M.; Martınez-Dueñas, Loreto; Ubiña, Sara; Segovia, J.L.; Marco, Carmen

doi:10.1016/j.lfs.2005.11.011

Cited by 6 publications

(4 citation statements)

References 32 publications

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“…In rats, chronic administration of ethanol increased the V d of procainamide, a drug that shares structural and chemical similarities with nicotine (Gole and Nagwekar, 1991), consistent with the possibility that ethanol can increase nicotine V d . The potential effect of ethanol on nicotine V d may be explained by ethanol's effect on cell membrane structure and permeability and epithelial barrier function (Nanji et al, 1994;Bor et al, 1998Bor et al, , 1998Carrasco et al, 2006Carrasco et al, , 2007. An increase in nicotine V d can explain the decrease in nicotine C max observed in the ethanol-exposed animals, but cannot account for the observed decreased in nicotine AUC 0-infinity .…”

Section: Discussionmentioning

confidence: 99%

Differential Effects of Nicotine Treatment and Ethanol Self-Administration on CYP2A6, CYP2B6 and Nicotine Pharmacokinetics in African Green Monkeys

Ferguson

Miksys

Palmour

et al. 2012

J Pharmacol Exp Ther

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In primates, nicotine is metabolically inactivated in the liver by CYP2A6 and possibly CYP2B6. Changes in the levels of these two enzymes may affect nicotine pharmacokinetics and influence smoking behaviors. This study investigated the independent and combined effects of ethanol self-administration and nicotine treatment (0.5 mg/kg b.i.d. s.c.) on hepatic CYP2A6 and CYP2B6 levels (mRNA, protein, and enzymatic activity), in vitro nicotine metabolism, and in vivo nicotine pharmacokinetics in monkeys. CYP2A6 mRNA and protein levels and in vitro coumarin (selective CYP2A6 substrate) and nicotine metabolism were decreased by nicotine treatment but unaffected by ethanol. CYP2B6 protein levels and in vitro bupropion (selective CYP2B6 substrate) metabolism were increased by ethanol but unaffected by nicotine treatment; CYP2B6 mRNA levels were unaltered by either treatment. Combined ethanol and nicotine exposure decreased CYP2A6 mRNA and protein levels, as well as in vitro coumarin and nicotine metabolism, and increased CYP2B6 protein levels and in vitro bupropion metabolism, with no change in CYP2B6 mRNA levels. Chronic nicotine resulted in higher nicotine plasma levels achieved after nicotine administration, consistent with decreased CYP2A6. Ethanol alone, or combined with nicotine, resulted in lower nicotine plasma levels by a mechanism independent of the change in these enzymes. Thus, nicotine can decrease hepatic CYP2A6, reducing the metabolism of its substrates, including nicotine, whereas ethanol can increase hepatic CYP2B6, increasing the metabolism of CYP2B6 substrates. In vivo nicotine pharmacokinetics are differentially affected by ethanol and nicotine, but when both drugs are used in combination the effect more closely resembles ethanol alone.

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Section: Discussionmentioning

confidence: 99%

Differential Effects of Nicotine Treatment and Ethanol Self-Administration on CYP2A6, CYP2B6 and Nicotine Pharmacokinetics in African Green Monkeys

Ferguson

Miksys

Palmour

et al. 2012

J Pharmacol Exp Ther

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“…Therefore, interorganelle translocation of aminoglycerophospholipids can be investigated by following the incorporation of serine into PS in the ER, decarboxylation of PS to PE in the mitochondria, and methylation of PE to PC upon the return of PE to the ER without isolation of organelles. Making use of this experimental strategy, phospholipid transport studies with intact cells, isolated organelles, and permeabilized cells have been performed (Butler and Thompson 1975;Voelker 1985Voelker , 1989aVoelker ,b, 1990Voelker , 1991Vance 1990;Achleitner et al 1995;Shiao et al 1995;Emoto et al 1999;Kuge et al 2001;Schumacher et al 2002;Wu and Voelker 2004;Carrasco et al 2006;Riekhof and Voelker 2006;Kornmann et al 2009;Nguyen et al 2012;Padilla-Ló pez et al 2012;Tamura et al 2012). These studies showed that in mammalian cells PS transport from MAM to the OMM requires ATP.…”

Section: Transport Of Phospholipids Between the Endoplasmic Reticulummentioning

confidence: 99%

Lipid Transport between the Endoplasmic Reticulum and Mitochondria

Flis

Daum

2013

Cold Spring Harbor Perspectives in Biology

165

127

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Mitochondria are partially autonomous organelles that depend on the import of certain proteins and lipids to maintain cell survival and membrane formation. Although phosphatidylglycerol, cardiolipin, and phosphatidylethanolamine are synthesized by mitochondrial enzymes, phosphatidylcholine, phosphatidylinositol, phosphatidylserine, and sterols need to be imported from other organelles. The origin of most lipids imported into mitochondria is the endoplasmic reticulum, which requires interaction of these two subcellular compartments. Recently, protein complexes that are involved in membrane contact between endoplasmic reticulum and mitochondria were identified, but their role in lipid transport is still unclear. In the present review, we describe components involved in lipid translocation between the endoplasmic reticulum and mitochondria and discuss functional as well as regulatory aspects that are important for lipid homeostasis.

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“…Among the noxious effects of alcohol are: a) damage to the mitochondria with the subsequent decrease in ATP levels (16,17); b) changes in membrane fluidity by interaction with either phospholipids or proteins (18,19); c) malnutrition (20); d) hypoxia in the pericentral zone of the liver acinus as oxygen is consumed in order to detoxify ethanol via oxidation (7); e) altered cytokine production (e.g. TNFα and TGFβ) (21,22); f) induction of 'leaky gut' with translocation of bacterial-derived endotoxin (LPS), the consequent activation of Kupffer cells, and the release of other soluble mediators and ROS (23,24); and g) impairment of the antioxidant defense (17,25).…”

Section: Alcoholic Liver Diseasementioning

confidence: 99%

Hepatic stellate cells and alcoholic liver disease

Vera

Nieto

2006

Rev. esp. enferm. dig.

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Liver fibrosis represents a significant health problem worldwide for which no effective therapy exists. A great deal of research has been carried out to understand the molecular mechanisms responsible for the development of liver fibrosis. Activated stellate cells are the primary cell type responsible for the production of collagen I, the key protein involved in the development of liver fibrosis. Excessive deposition of collagen I occurs along with impaired extracellular matrix remodeling. Following a fibrogenic stimulus stellate cells transform into an activated collagen type I-producing cell. Numerous changes in gene expression are associated with stellate cell activation, including the induction of several intracellular signaling cascades, which help maintain the activated phenotype and control the fibrogenic and proliferative state of the cell. Activation of stellate cells is mediated by factors released from hepatocytes and Kupffer cells as they produce reactive oxygen species, nitric oxide, cytokines, growth factors, and cyclooxygenase and lipoxygenase metabolites, which provide pivotal paracrine effects in the liver milieu. Inhibition of stellate cell activation, proliferation, and the increased production of extracellular matrix (i.e. collagen type I) are therefore crucial steps for intervention in hepatic fibrogenesis. 675 LIVER DISEASE REV ESP ENFERM DIG 2006; 98(9): 674-684 14. Lieber CS. Cytochrome P-4502E1: its physiological and pathological role. Physiol Rev 1997; 77: 517-44. 15. Lieber CS. The discovery of the microsomal ethanol oxidizing sys-Vol. 98. N.°9, 2006 HEPATIC STELLATE CELLS AND ALCOHOLIC 677 LIVER DISEASE REV ESP ENFERM DIG 2006; 98(9): 674-684

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Ethanol specifically alters the synthesis, acylation and transbilayer movement of aminophospholipids in rat-liver microsomes

Cited by 6 publications

References 32 publications

Differential Effects of Nicotine Treatment and Ethanol Self-Administration on CYP2A6, CYP2B6 and Nicotine Pharmacokinetics in African Green Monkeys

Differential Effects of Nicotine Treatment and Ethanol Self-Administration on CYP2A6, CYP2B6 and Nicotine Pharmacokinetics in African Green Monkeys

Lipid Transport between the Endoplasmic Reticulum and Mitochondria

Hepatic stellate cells and alcoholic liver disease

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