Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
May-2017 Volume 15 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
May-2017 Volume 15 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Inhibition of aldose reductase ameliorates ethanol‑induced steatosis in HepG2 cells

  • Authors:
    • Longxin Qiu
    • Chengchao Cai
    • Xiangqian Zhao
    • Yan Fang
    • Weibiao Tang
    • Chang Guo
  • View Affiliations / Copyright

    Affiliations: Department of Biological Science and Technology, School of Life Sciences, Longyan University, Longyan, Fujian 364012, P.R. China
  • Pages: 2732-2736
    |
    Published online on: March 10, 2017
       https://doi.org/10.3892/mmr.2017.6313
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Aldose reductase (AR) expression is increased in liver tissue of patients with ethanol‑induced liver disease. However, the exact role of AR in the development of ethanol‑induced liver disease has yet to be elucidated. The present study aimed to determine the effect of an AR inhibitor on ethanol‑induced steatosis in HepG2 cells and to identify possible underlying molecular mechanisms. Steatosis was induced in HepG2 cells by stimulating cells with 100 mM absolute ethanol for 48 h. Oil Red O staining was used to detect the lipid droplet accumulation in cells. Western blot analyses were used to determine protein expression levels and reverse transcription‑quantitative polymerase chain reaction was used to analyze mRNA expression levels. The results showed that AR protein expression was elevated in HepG2 cells stimulated with ethanol. HepG2 cells exhibited marked improvement of ethanol‑induced lipid accumulation following treatment with the AR inhibitor zopolrestat. Phosphorylation levels of 5' adenosine monophosphate‑activated protein kinase (AMPK) were markedly higher, whereas the mRNA expression levels of sterol‑regulatory element‑binding protein (SREBP)‑1c and fatty acid synthase (FAS) were significantly lower in zopolrestat‑treated and ethanol‑stimulated HepG2 cells compared with in untreated ethanol‑stimulated HepG2 cells. In addition, zopolrestat inhibited the ethanol‑induced expression of tumor necrosis factor (TNF)‑α. These results suggested that zopolrestat attenuated ethanol‑induced steatosis by activating AMPK and subsequently inhibiting the expression of SREBP‑1c and FAS, and by suppressing the expression of TNF‑α in HepG2 cells.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Hers HG: Aldose reductase. Biochim Biophys Acta. 37:120–126. 1960.(In French). View Article : Google Scholar : PubMed/NCBI

2 

Clements RS Jr: The polyol pathway. A historical review. Drugs. 32:(Suppl 2). S3–S5. 1986. View Article : Google Scholar

3 

Ferraris JD, Williams CK, Jung KY, Bedford JJ, Burg MB and García-Pérez A: ORE, a eukaryotic minimal essential osmotic response element. The aldose reductase gene in hyperosmotic stress. J Biol Chem. 271:18318–18321. 1996. View Article : Google Scholar : PubMed/NCBI

4 

Yabe-Nishimura C: Aldose reductase in glucose toxicity: A potential target for the prevention of diabetic complications. Pharmacol Rev. 50:21–33. 1998.PubMed/NCBI

5 

Nishimura-Yabe C: Aldose reductase in the polyol pathway: A potential target for the therapeutic intervention of diabetic complications. Nihon Yakurigaku Zasshi. 111:137–145. 1998.(In Japanese). View Article : Google Scholar : PubMed/NCBI

6 

Clements RS Jr, Weaver JP and Winegrad AI: The distribution of polyol: NADP oxidoreductase in mammalian tissues. Biochem Biophys Res Commun. 37:347–353. 1969. View Article : Google Scholar : PubMed/NCBI

7 

Markus HB, Raducha M and Harris H: Tissue distribution of mammalian aldose reductase and related enzymes. Biochem Med. 29:31–45. 1983. View Article : Google Scholar : PubMed/NCBI

8 

Qiu L, Lin J, Xu F, Gao Y, Zhang C, Liu Y, Luo Y and Yang JY: Inhibition of aldose reductase activates hepatic peroxisome proliferator-activated receptor-α and ameliorates hepatosteatosis in diabetic db/db mice. Exp Diabetes Res. 2012:7897302012. View Article : Google Scholar : PubMed/NCBI

9 

Qiu L, Lin J, Ying M, Chen W, Yang J, Deng T, Chen J, Shi D and Yang JY: Aldose reductase is involved in the development of murine diet-induced nonalcoholic steatohepatitis. PLoS One. 8:e735912013. View Article : Google Scholar : PubMed/NCBI

10 

Chen T, Shi D, Chen J, Yang Y, Qiu M, Wang W and Qiu L: Inhibition of aldose reductase ameliorates diet-induced nonalcoholic steatohepatitis in mice via modulating the phosphorylation of hepatic peroxisome proliferator-activated receptor α. Mol Med Rep. 11:303–308. 2015.PubMed/NCBI

11 

Brown KE, Broadhurst KA, Mathahs MM, Kladney RD, Fimmel CJ, Srivastava SK and Brunt EM: Immunodetection of aldose reductase in normal and diseased human liver. Histol Histopathol. 20:429–436. 2005.PubMed/NCBI

12 

O'Connor T, Ireland LS, Harrison DJ and Hayes JD: Major differences exist in the function and tissue-specific expression of human aflatoxin B1 aldehyde reductase and the principal human aldo-keto reductase AKR1 family members. Biochem J 343 Pt. 2:487–504. 1999. View Article : Google Scholar

13 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

14 

Keegan A, Martini R and Batey R: Ethanol-related liver injury in the rat: A model of steatosis, inflammation and pericentral fibrosis. J Hepatol. 23:591–600. 1995. View Article : Google Scholar : PubMed/NCBI

15 

Altamirano J and Bataller R: Alcoholic liver disease: Pathogenesis and new targets for therapy. Nat Rev Gastroenterol Hepatol. 8:491–501. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Sid B, Verrax J and Calderon PB: Role of AMPK activation in oxidative cell damage: Implications for alcohol-induced liver disease. Biochem Pharmacol. 86:200–209. 2013. View Article : Google Scholar : PubMed/NCBI

17 

You M, Matsumoto M, Pacold CM, Cho WK and Crabb DW: The role of AMP-activated protein kinase in the action of ethanol in the liver. Gastroenterology. 127:1798–1808. 2004. View Article : Google Scholar : PubMed/NCBI

18 

Horton JD, Goldstein JL and Brown MS: SREBPs: Activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest. 109:1125–1131. 2002. View Article : Google Scholar : PubMed/NCBI

19 

Roder K, Zhang L and Schweizer M: SREBP-1c mediates the retinoid-dependent increase in fatty acid synthase promoter activity in HepG2. FEBS Lett. 581:2715–2720. 2007. View Article : Google Scholar : PubMed/NCBI

20 

Kong L, Ren W, Li W, Zhao S, Mi H, Wang R, Zhang Y, Wu W, Nan Y and Yu J: Activation of peroxisome proliferator activated receptor alpha ameliorates ethanol induced steatohepatitis in mice. Lipids Health Dis. 10:2462011. View Article : Google Scholar : PubMed/NCBI

21 

Kota BP, Huang TH and Roufogalis BD: An overview on biological mechanisms of PPARs. Pharmacol Res. 51:85–94. 2005. View Article : Google Scholar : PubMed/NCBI

22 

Thiele DL: Tumor necrosis factor, the acute phase response and the pathogenesis of alcoholic liver disease. Hepatology. 9:497–499. 1989. View Article : Google Scholar : PubMed/NCBI

23 

Kawaratani H, Tsujimoto T, Douhara A, Takaya H, Moriya K, Namisaki T, Noguchi R, Yoshiji H, Fujimoto M and Fukui H: The effect of inflammatory cytokines in alcoholic liver disease. Mediators Inflamm. 2013:4951562013. View Article : Google Scholar : PubMed/NCBI

24 

Viollet B, Guigas B, Leclerc J, Hébrard S, Lantier L, Mounier R, Andreelli F and Foretz M: AMP-activated protein kinase in the regulation of hepatic energy metabolism: From physiology to therapeutic perspectives. Acta Physiol (Oxf). 196:81–98. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Tomita K, Tamiya G, Ando S, Kitamura N, Koizumi H, Kato S, Horie Y, Kaneko T, Azuma T, Nagata H, et al: AICAR, an AMPK activator, has protective effects on alcohol-induced fatty liver in rats. Alcohol Clin Exp Res. 29:(12 Suppl). S240–S245. 2005. View Article : Google Scholar

26 

Shimano H, Horton JD, Shimomura I, Hammer RE, Brown MS and Goldstein JL: Isoform 1c of sterol regulatory element binding protein is less active than isoform 1a in livers of transgenic mice and in cultured cells. J Clin Invest. 99:846–854. 1997. View Article : Google Scholar : PubMed/NCBI

27 

Lluis JM, Colell A, García-Ruiz C, Kaplowitz N and Fernández-Checa JC: Acetaldehyde impairs mitochondrial glutathione transport in HepG2 cells through endoplasmic reticulum stress. Gastroenterology. 124:708–724. 2003. View Article : Google Scholar : PubMed/NCBI

28 

You M, Fischer M, Deeg MA and Crabb DW: Ethanol induces fatty acid synthesis pathways by activation of sterol regulatory element-binding protein (SREBP). J Biol Chem. 277:29342–29347. 2002. View Article : Google Scholar : PubMed/NCBI

29 

You M and Crabb DW: Recent advances in alcoholic liver disease II. Minireview: Molecular mechanisms of alcoholic fatty liver. Am J Physiol Gastrointest Liver Physiol. 287:G1–G6. 2004. View Article : Google Scholar : PubMed/NCBI

30 

McClain CJ and Cohen DA: Increased tumor necrosis factor production by monocytes in alcoholic hepatitis. Hepatology. 9:349–351. 1989. View Article : Google Scholar : PubMed/NCBI

31 

Endo M, Masaki T, Seike M and Yoshimatsu H: TNF-alpha induces hepatic steatosis in mice by enhancing gene expression of sterol regulatory element binding protein-1c (SREBP-1c). Exp Biol Med (Maywood). 232:614–621. 2007.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Qiu L, Cai C, Zhao X, Fang Y, Tang W and Guo C: Inhibition of aldose reductase ameliorates ethanol‑induced steatosis in HepG2 cells. Mol Med Rep 15: 2732-2736, 2017.
APA
Qiu, L., Cai, C., Zhao, X., Fang, Y., Tang, W., & Guo, C. (2017). Inhibition of aldose reductase ameliorates ethanol‑induced steatosis in HepG2 cells. Molecular Medicine Reports, 15, 2732-2736. https://doi.org/10.3892/mmr.2017.6313
MLA
Qiu, L., Cai, C., Zhao, X., Fang, Y., Tang, W., Guo, C."Inhibition of aldose reductase ameliorates ethanol‑induced steatosis in HepG2 cells". Molecular Medicine Reports 15.5 (2017): 2732-2736.
Chicago
Qiu, L., Cai, C., Zhao, X., Fang, Y., Tang, W., Guo, C."Inhibition of aldose reductase ameliorates ethanol‑induced steatosis in HepG2 cells". Molecular Medicine Reports 15, no. 5 (2017): 2732-2736. https://doi.org/10.3892/mmr.2017.6313
Copy and paste a formatted citation
x
Spandidos Publications style
Qiu L, Cai C, Zhao X, Fang Y, Tang W and Guo C: Inhibition of aldose reductase ameliorates ethanol‑induced steatosis in HepG2 cells. Mol Med Rep 15: 2732-2736, 2017.
APA
Qiu, L., Cai, C., Zhao, X., Fang, Y., Tang, W., & Guo, C. (2017). Inhibition of aldose reductase ameliorates ethanol‑induced steatosis in HepG2 cells. Molecular Medicine Reports, 15, 2732-2736. https://doi.org/10.3892/mmr.2017.6313
MLA
Qiu, L., Cai, C., Zhao, X., Fang, Y., Tang, W., Guo, C."Inhibition of aldose reductase ameliorates ethanol‑induced steatosis in HepG2 cells". Molecular Medicine Reports 15.5 (2017): 2732-2736.
Chicago
Qiu, L., Cai, C., Zhao, X., Fang, Y., Tang, W., Guo, C."Inhibition of aldose reductase ameliorates ethanol‑induced steatosis in HepG2 cells". Molecular Medicine Reports 15, no. 5 (2017): 2732-2736. https://doi.org/10.3892/mmr.2017.6313
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team