Role of microRNAs in Alcohol-Induced Multi-Organ Injury

Natarajan, Sathish Kumar; Pachunka, Joseph; Mott, Justin L.

doi:10.3390/biom5043309

Cited by 52 publications

(45 citation statements)

References 178 publications

(271 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…MicroRNAs are a major class of molecular modulators in biology whose functions are mainly through gene repression. The role of microRNAs in alcohol-induced multi-organ injury have been implicated, such as in alcoholic liver disease (Gao and Bataller 2011;Miranda et al 2010;Natarajan et al 2015). The exploration for the possible involvement of microRNAs in ALDH2 gene modulation under ethanol exposure may be useful to treat patients with ACM.…”

Section: Introductionmentioning

confidence: 99%

Increased expression of microRNA-378a-5p in acute ethanol exposure of rat cardiomyocytes

Wang

Song

Zhang

et al. 2017

Cell Stress and Chaperones

View full text Add to dashboard Cite

Alcohol abuse is a risk factor for a distinct form of congestive heart failure, known as alcoholic cardiomyopathy (ACM). Here, we investigate how microRNAs may participate in the induction of cardiomyocyte apoptosis associated with ethanol exposure in vitro. Increasing the concentrations of ethanol to primary rat cardiomyocytes resulted in elevated apoptosis assessed by annexin V and propidium iodide staining, and reduced expression of an enzyme for alcohol detoxification aldehyde dehydrogenase 2 (ALDH2). These ethanol effects were accompanied by a substantial elevation of miR378a-5p. Driving miR-378a-5p overexpression in cardiomyocytes decreased ALDH2. The specific interaction of miR-378a-5p with the 3'UTR of ALDH2 was examined by luciferase reporter assays, and we found that miR-378a-5p activity depends on a complementary base pairing at the 3′-UTR region of ALDH2 mRNA. Finally, ethanol-induced apoptosis in cardiomyocytes was attenuated in the presence of anti-miR378a-5p. Collectively, these data implicate a likely involvement of miR-378a-5p in the stimulation of cardiomyocyte apoptosis through ALDH2 gene suppression, which might play a potential role in the pathogenesis of ACM.

show abstract

Section: Introductionmentioning

confidence: 99%

Increased expression of microRNA-378a-5p in acute ethanol exposure of rat cardiomyocytes

Wang

Song

Zhang

et al. 2017

Cell Stress and Chaperones

View full text Add to dashboard Cite

show abstract

“…In mice, administration of the butyrate recovers the intestinal barrier function in all stages of alcohol exposure, but the liver injury was reduced only in case of acute or short-term alcohol exposure [9]. In alcohol-fed mice, induction of long chain fatty acids (LCFAs) reduces ALD by escalating the levels of Lactobacillus spp., improving intestinal barrier function and reducing intestinal inflammation [10]. After chronic alcohol feeding, microbial metabolites blend together with small amounts of Lactobacillus also reduces intestinal barrier dysfunction and ALD.…”

Section: Figure 1: Mechanism Of Alcoholic Liver Disease Ethanol Expomentioning

confidence: 99%

Potential Molecular Mechanism of Probiotics in Alcoholic Liver Disease

Patel¹,

Patel²,

Palash³

2017

J Alcohol Drug Depend

View full text Add to dashboard Cite

Alcohol consumption and its abuse are significant prevalent cause for liver diseases and death worldwide. Increased bacterial endotoxin in the portal circulation, the plasma ratio of liver enzymes like alanine aminotransferase (ALT), aspartate aminotransferase (AST) and triglyceride implies the symbiotic relation between the gut and liver plays a key function in alcoholic liver disease (ALD). Consumption of alcohol leads to gut dysbiosis and informalities of the intestinal barrier, hyper gut permeability, oxidative stress, inflammation and adversely affect adipose tissue metabolism, and those are mainly recognized as major factors for progression of alcoholic liver disease. Alteration of gut microbiota is referred to as bacterial overgrowth which leads to the release of bacterial products to change in commercial/pathogenic microbiota equilibrium. Lipopolysaccharide (LPS) derived inflammatory signal renders inflammation in alcoholic liver disease. Increase in concentration of lipopolysaccharide leads to activation of toll-like receptor 4 (TLR4) and alteration in micro RNA (miRNA) expression at the transcription level. Activation of myeloid differentiation factor 88 (MyD88) pathways eventually produces pro inflammatory cytokine activation that is an important mediator of alcoholic liver disease. However, there is no effectual Food and Drug Administration (FDA) approved treatment for any stage of alcoholic liver disease. Thus, the potential therapeutic approach for alcoholic liver disease is restoration and alteration of gut microbiota. With the increasing importance of gut microbiota in the onset and occurrence of a variety of diseases, the potential use of probiotics in ALD is receiving more exploration and clinical attention. Probiotic administration is nontoxic, inexpensive and noninvasive strategy with minimal side effects compared to antibiotic therapy and surgery. Yet, there is no substantial evidence on the efficient molecular mechanism regarding mode of action of probiotics on ALD as therapeutics. This review summarizes the research done on gut liver-axis and potential mechanism of probiotic in alcoholic liver disease.

show abstract

“…Mechanism comprised in pathophysiology of alcoholic cardiomyopathy include oxidative stress, cell apoptosis, calcium ion homeostasis impairment, mitochondrial dysfunction, fatty acid metabolism derangement and impaired transportation together with accelerated protein catabolism and autophagy 39. Chronic alcohol consumption results in reduction of gap junction proteins, decreased size of myocytes and alteration in myocardial conduction, which causes increased cardiac remodelling, and together with apoptosis, thinning of the ventricular wall 41 42. Acute alcohol consumption also decreases atrial current densities 41.…”

Section: Alcoholic Heart Disease and Alcoholic Liver Cirrhosismentioning

confidence: 99%

“…Chronic alcohol consumption results in reduction of gap junction proteins, decreased size of myocytes and alteration in myocardial conduction, which causes increased cardiac remodelling, and together with apoptosis, thinning of the ventricular wall 41 42. Acute alcohol consumption also decreases atrial current densities 41. Symptoms in patients with alcoholic cardiomyopathy include arrhythmias and heart failure, and are in accordance with reduced cardiac output 11.…”

Section: Alcoholic Heart Disease and Alcoholic Liver Cirrhosismentioning

confidence: 99%

Cardiac manifestations in alcoholic liver disease

Milić

Lulić

Štimac

et al. 2016

Postgraduate Medical Journal

View full text Add to dashboard Cite

Alcoholic liver disease is the most prevalent cause of progressive liver disease in Europe. Alcoholic cirrhosis occurs in 8%-20% of cases of alcoholic liver disease. It has significant influence on cardiovascular system and haemodynamics through increased heart rate, cardiac output, decreased systemic vascular resistance, arterial pressure and plasma volume expansion. Cirrhotic cardiomyopathy is characterised by systolic and diastolic dysfunction and electrophysiological abnormalities, if no other underlying cardiac disease is present. It is often unmasked only during pharmacological or physiological stress, when compensatory mechanisms of the heart become insufficient to maintain adequate cardiac output. Low-to-moderate intake of alcohol can be cardioprotective. However, heavy drinking is associated with an increased risk of cardiovascular diseases, such as alcoholic cardiomyopathy, arterial hypertension, atrial arrhythmias as well as haemorrhagic and ischaemic stroke. Alcoholic cardiomyopathy is characterised by dilated left ventricle (LV), increased LV mass, normal or reduced LV wall thickness and systolic dysfunction.

show abstract

Role of microRNAs in Alcohol-Induced Multi-Organ Injury

Cited by 52 publications

References 178 publications

Increased expression of microRNA-378a-5p in acute ethanol exposure of rat cardiomyocytes

Increased expression of microRNA-378a-5p in acute ethanol exposure of rat cardiomyocytes

Potential Molecular Mechanism of Probiotics in Alcoholic Liver Disease

Cardiac manifestations in alcoholic liver disease

Contact Info

Product

Resources

About