ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2015
Zinc deficiency mediates alcohol-induced apoptotic cell death in the liver of rats through activating ER and mitochondrial cell death pathways.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 65 citations in OpenAlex.
- ZnT6-mediated ZnMolecular and cellular biochemistry · 2025Article
- Mitochondrial oxidative stress inhibited Sirt3/Foxo3/PPARα pathway and aggravated copper and zinc co-deficiency-induced hepatic lipotoxicity in a fish model.Cellular and molecular life sciences : CMLS · 2025Article
- Toxicity and Hepatoprotective Effects of ZnO Nanoparticles on Normal and High-Fat Diet-Fed Rat Livers: Mechanism of Action.Biological trace element research · 2025Article
- Structural insights into human zinc transporter ZnT1 mediated ZnEMBO reports · 2024Article
- Reversal of hepatic accumulation of nordeoxycholic acid underlines the beneficial effects of cholestyramine on alcohol-associated liver disease in mice.Hepatology communications · 2024Article
- The Anti-Oxidative, Anti-Inflammatory, Anti-Apoptotic, and Anti-Necroptotic Role of Zinc in COVID-19 and Sepsis.Antioxidants (Basel, Switzerland) · 2023Review
- Zinc Deficiency Exacerbates Bisphenol A-Induced Hepatic and Renal Damage: Delineation of Molecular Mechanisms.Biological trace element research · 2023Article
- Therapeutic Pipeline in Alcohol-Associated Liver Disease.Seminars in liver disease · 2023Review
- Mitochondrial Metal Ion Transport in Cell Metabolism and Disease.International journal of molecular sciences · 2021Review
- Functional Analysis of the Promoter Regions of Two Apoptosis-Related Genes (International journal of molecular sciences · 2021Article
- The Multifaceted Roles of Zinc in Neuronal Mitochondrial Dysfunction.Biomedicines · 2021Review
- The role of labile ZnMolecular and cellular biochemistry · 2021Review
- Magnesium, Calcium, Potassium, Sodium, Phosphorus, Selenium, Zinc, and Chromium Levels in Alcohol Use Disorder: A Review.Journal of clinical medicine · 2020Review
- The knowns and unknowns of treatment for alcoholic hepatitis.The lancet. Gastroenterology & hepatology · 2020Review
- Endoplasmic reticulum targeting fluorescent probes to image mobile ZnChemical science · 2019Article
- Article
- SLC39A8 gene encoding a metal ion transporter: discovery and bench to bedside.Human genomics · 2019Review
- Review
- Zinc deficiency as a mediator of toxic effects of alcohol abuse.European journal of nutrition · 2018Review
- Hepatic ZIP8 deficiency is associated with disrupted selenium homeostasis, liver pathology, and tumor formation.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Hepatic zinc deficiency has been well documented in alcoholic patients, but the mechanisms by which zinc deficiency mediates cell death have not been well defined. The objectives of this study were to determine whether alcohol perturbs subcellular zinc homeostasis and how organelle zinc depletion may link with cell death pathways. Wistar rats were pair-fed with the Lieber-DeCarli control or ethanol diet for 5 mo. Chronic alcohol exposure significantly reduced zinc level in isolated hepatic endoplasmic reticulum (ER) and mitochondria. Among the detected zinc transporters, ER Zrt/Irt-like protein (ZIP)13 and mitochondrial ZIP8, which transport zinc from ER and mitochondria to cytosol, were significantly increased. Mitochondrial zinc transporter (ZnT) 4, which transports zinc from cytosol to mitochondria, was also increased. ER phosphorylated eukaryotic initiation factor 2α, activating transcription factor 4, and C/EBP homologous protein were significantly upregulated, and mitochondrial cytochrome c release and Bax insertion were detected in association with caspase-3 activation and apoptotic cell death. To define the role of zinc deficiency in ER and mitochondrial stress, H4IIEC3 cells were treated with 3 μM N,N,N',N'-tetrakis (2-pyridylmethyl) ethylenediamine for 6 h with or without supplementation with zinc or N-acetylcysteine (NAC). The results demonstrated that zinc deprivation induced caspase-3 activation and apoptosis in association with ER and mitochondria dysfunction, which were inhibited by zinc as low as 10 μM but not by 2 mM NAC. These results suggest that chronic ethanol exposure induced in ER and mitochondrial zinc deficiency might activate intrinsic cell death signaling pathway, which could not be effectively rescued by antioxidant treatment.
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