Current Molecular Pharmacology - Volume 10, Issue 3, 2017

This article reviews recent studies on CYP2E1-mediated alcoholic liver injury, the induction of CYP2A5 by alcohol and the mechanism for this upregulation, especially the permissive role of CYP2E1 in the induction of CYP2A5 by alcohol and the CYP2E1-ROS-Nrf2 pathway, and protective effects of CYP2A5 against ethanol-induced oxidative liver injury. Ethanol can induce CYP2E1, an active generator of reactive oxygen spe Read More

Here, we describe research on the involvement of the transcription factor, Early Growth Response- 1 (Egr-1) in alcohol-induced liver injury, specifically, fatty liver (steatosis), one of the earliest and most frequent signs of liver injury that occurs after heavy drinking. Egr-1 is a ubiquitous transcription factor found in nearly all cell types. However, because the liver is the principal site of ethanol oxidation, it sustains the grea Read More

The Wnt pathway is a highly conserved signal transduction pathway that plays an important role in diverse aspects of hepatic physiology. The Wnt pathway, consisting of canonical and noncanonical arms, is composed of secreted glycoproteins, cell surface receptors and co-receptors, and complex intracellular regulatory machinery that regulate a large number of cellular functions.β-Catenin is the main effector of the cano Read More

Chronic alcohol consumption can lead to the development of alcoholic fatty liver disease. The underlying pathogenic mechanisms however, have not been fully elucidated. Here, we review the current state of the art regarding the application of lipidomics to study alcohol's effect on hepatic lipids. It is clear that alcohol has a profound effect on the hepatic lipidome, with documented changes in the major lipid categories (i.e. f Read More

Alcoholic fatty liver disease (AFLD) and non-alcoholic fatty liver disease (NAFLD) are two pathological conditions that are spreading worldwide. Both conditions are remarkably similar with regard to the pathophysiological mechanism and progression despite different causes. Oxidative stressinduced mitochondrial dysfunction through post-translational protein modifications and/or mitochondrial DNA damage has been a Read More

Lipin-1, a mammalian phosphatidic acid phosphatase (PAP), is a bi-functional molecule involved in various signaling pathways via its function as a PAP enzyme in the triglyceride synthesis pathway and in the nucleus as a transcriptional co-regulator. In the liver, lipin-1 is known to play a vital role in controlling the lipid metabolism and inflammation process at multiple regulatory levels. Alcoholic fatty liver disease (AFLD) is one of th Read More

For more than 30 years, lipid droplets (LDs) were considered as an inert bag of lipid for storage of energy-rich fat molecules. Following a paradigm shift almost a decade ago, LDs are presently considered an active subcellular organelle especially designed for assembling, storing and subsequently supplying lipids for generating energy and membrane synthesis (and in the case of hepatocytes for VLDL secretion). LDs al Read More

Introduction: Ethanol metabolism in the liver results in oxidative stress, altered cytokine production and fat accumulation in the liver. Thus, it is thought that the accumulation of benign fat into the liver in conjunction with a “second hit” leads to liver failure. However, we have recently developed the use of precision-cut liver slices (PCLSs) as an in vitro culture model in which to investigate the pathophysiology of alcohol- Read More