Alcohol and Apoptosis: Friends or Foes?

Rodríguez, Ana B.; Chawla, Karan; Umoh, Nsini; Cousins, Valerie; Ketegou, Assama; Reddy, Madhumati G.; AlRubaiee, Mustafa; Haddad, Georges E.; Burke, Mark W.

doi:10.3390/biom5043193

Cited by 34 publications

(28 citation statements)

References 31 publications

(54 reference statements)

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“…During the alcohol exposure, the cellular signaling pathway, which regulates cell proliferation and survival, is inhibited. Previous reports showed that alcohol suppressed the PI3K/AKT signaling pathway in liver cells [52,53]. However, it is still unclear to determine the level of inner ear alcohol content by alcohol exposure in BAC of alcohol content.…”

Section: Discussionmentioning

confidence: 97%

Impaired Glycolysis Promotes Alcohol Exposure-Induced Apoptosis in HEI-OC1 Cells via Inhibition of EGFR Signaling

Kang

Choi

Park

et al. 2020

IJMS

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Glucose metabolism is an important metabolic pathway in the auditory system. Chronic alcohol exposure can cause metabolic dysfunction in auditory cells during hearing loss. While alcohol exposure has been linked to hearing loss, the mechanism by which impaired glycolysis promotes cytotoxicity and cell death in auditory cells remains unclear. Here, we show that the inhibition of epidermal growth factor receptor (EGFR)-induced glycolysis is a critical mechanism for alcohol exposure-induced apoptosis in HEI-OC1 cells. The cytotoxicity via apoptosis was significantly increased by alcohol exposure in HEI-OC1 cells. The glycolytic activity and the levels of hexokinase 1 (HK1) were significantly suppressed by alcohol exposure in HEI-OC1 cells. Mechanistic studies showed that the levels of EGFR and AKT phosphorylation were reduced by alcohol exposure in HEI-OC1 cells. Notably, HK1 expression and glycolytic activity was suppressed by EGFR inhibition in HEI-OC1 cells. These results suggest that impaired glycolysis promotes alcohol exposure-induced apoptosis in HEI-OC1 cells via the inhibition of EGFR signaling.

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Section: Discussionmentioning

confidence: 97%

Impaired Glycolysis Promotes Alcohol Exposure-Induced Apoptosis in HEI-OC1 Cells via Inhibition of EGFR Signaling

Kang

Choi

Park

et al. 2020

IJMS

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“…Specifically, alcohol increased caspase 3 staining (4–5 months liquid diet) in male Wistar rats (99) and caspase 3 protein and activity in alcohol-fed male mice (15, 57). Acutely, cleaved caspase-3 was also increased by alcohol (3g/kg/day, 3 days) in male mice (95).…”

Section: Apoptosismentioning

confidence: 99%

Etiology of alcoholic cardiomyopathy: Mitochondria, oxidative stress and apoptosis

Steiner

Lang

2017

The International Journal of Biochemistry & Cell Biology

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Putative mechanisms leading to the development of alcoholic cardiomyopathy (ACM) include the interrelated cellular processes of mitochondria metabolism, oxidative stress and apoptosis. As mitochondria fuel the constant energy demands of this continually contracting tissue, it is not surprising that alcohol-induced molecular changes in this organelle contribute to cardiac dysfunction and ACM. As the causal relationship of these processes with ACM has already been established, the primary objective of this review is to provide an update of the experimental findings to more completely understand the aforementioned mechanisms. Accordingly, recent data indicate that alcohol impairs mitochondria function assessed by membrane potential and respiratory chain activity. Indictors of oxidative stress including superoxide dismutase, glutathione metabolites and malondialdehyde are also adversely affected by alcohol oftentimes in a sex-dependent manner. Additionally, myocardial apoptosis is increased based on assessment of TUNEL staining and caspase activity. Recent work has also emerged linking alcohol-induced oxidative stress with apoptosis providing new insight on the codependence of these interrelated mechanisms in ACM. Attention is also given to methodological differences including the dose of alcohol, experimental model system and the use of males versus females to highlight inconsistencies and areas that would benefit from establishment of a consistent model.

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“…Myocyte loss by necrosis or apoptosis is a relevant mechanism in cardiac dysfunction and is present in major heart diseases [70]. High-dose alcohol consumption has clearly shown to increase cardiac apoptosis pathways in animal [23] and human studies [24]. Thus, pro-apoptotic mechanisms are activated in alcoholic patients without heart damage.…”

Section: Strategies To Decrease Factors Inducing Heart Damagementioning

confidence: 99%

“…Thus, pro-apoptotic mechanisms are activated in alcoholic patients without heart damage. Chronic alcoholic subjects with structural heart damage showed higher apoptotic indexes in deoxyribonucleotidyl transferase-mediated dUTP-biotin nick end-labeling, Bax, and Bcl-2 assays as compared with control subjects [23,24]. Since the control of myocyte apoptosis is a key factor in alcohol-induced heart damage [9], the most relevant strategies to control cardiac hypertrophy and myocyte loss include the following.…”

Section: Strategies To Decrease Factors Inducing Heart Damagementioning

confidence: 99%

New Treatment Strategies for Alcohol-Induced Heart Damage

Fernández‐Solà

Porta

2016

IJMS

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High-dose alcohol misuse induces multiple noxious cardiac effects, including myocyte hypertrophy and necrosis, interstitial fibrosis, decreased ventricular contraction and ventricle enlargement. These effects produce diastolic and systolic ventricular dysfunction leading to congestive heart failure, arrhythmias and an increased death rate. There are multiple, dose-dependent, synchronic and synergistic mechanisms of alcohol-induced cardiac damage. Ethanol alters membrane permeability and composition, interferes with receptors and intracellular transients, induces oxidative, metabolic and energy damage, decreases protein synthesis, excitation-contraction coupling and increases cell apoptosis. In addition, ethanol decreases myocyte protective and repair mechanisms and their regeneration. Although there are diverse different strategies to directly target alcohol-induced heart damage, they are partially effective, and can only be used as support medication in a multidisciplinary approach. Alcohol abstinence is the preferred goal, but control drinking is useful in alcohol-addicted subjects not able to abstain. Correction of nutrition, ionic and vitamin deficiencies and control of alcohol-related systemic organ damage are compulsory. Recently, several growth factors (myostatin, IGF-1, leptin, ghrelin, miRNA, and ROCK inhibitors) and new cardiomyokines such as FGF21 have been described to regulate cardiac plasticity and decrease cardiac damage, improving cardiac repair mechanisms, and they are promising agents in this field. New potential therapeutic targets aim to control oxidative damage, myocyte hypertrophy, interstitial fibrosis and persistent apoptosis In addition, stem-cell therapy may improve myocyte regeneration. However, these strategies are not yet approved for clinical use.

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Alcohol and Apoptosis: Friends or Foes?

Cited by 34 publications

References 31 publications

Impaired Glycolysis Promotes Alcohol Exposure-Induced Apoptosis in HEI-OC1 Cells via Inhibition of EGFR Signaling

Impaired Glycolysis Promotes Alcohol Exposure-Induced Apoptosis in HEI-OC1 Cells via Inhibition of EGFR Signaling

Etiology of alcoholic cardiomyopathy: Mitochondria, oxidative stress and apoptosis

New Treatment Strategies for Alcohol-Induced Heart Damage

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