Next Article in Journal
Clinical and Functional Assays of Radiosensitivity and Radiation-Induced Second Cancer
Next Article in Special Issue
Alcohol and Cancer Stem Cells
Previous Article in Journal
Advances in Precision Medicine: Tailoring Individualized Therapies
Previous Article in Special Issue
Alcohol and Hepatocellular Carcinoma: Adding Fuel to the Flame
Article Menu
Issue 11 (November) cover image

Export Article

Open AccessReview
Cancers 2017, 9(11), 145; https://doi.org/10.3390/cancers9110145

Does Hypoxia Cause Carcinogenic Iron Accumulation in Alcoholic Liver Disease (ALD)?

Center for Alcohol Research, University of Heidelberg and Salem Medical Center, 69120 Heidelberg, Germany
*
Authors to whom correspondence should be addressed.
Academic Editor: Samuel C. Mok
Received: 30 September 2017 / Revised: 19 October 2017 / Accepted: 20 October 2017 / Published: 25 October 2017
(This article belongs to the Special Issue Alcohol and Cancer)
View Full-Text   |   Download PDF [1973 KB, uploaded 25 October 2017]   |  

Abstract

Alcoholic liver disease (ALD) is a leading health risk worldwide. Hepatic iron overload is frequently observed in ALD patients and it is an important and independent factor for disease progression, survival, and the development of primary liver cancer (HCC). At a systemic level, iron homeostasis is controlled by the liver-secreted hormone hepcidin. Hepcidin regulation is complex and still not completely understood. It is modulated by many pathophysiological conditions associated with ALD, such as inflammation, anemia, oxidative stress/H2O2, or hypoxia. Namely, the data on hypoxia-signaling of hepcidin are conflicting, which seems to be mainly due to interpretational limitations of in vivo data and methodological challenges. Hence, it is often overlooked that hepcidin-secreting hepatocytes are physiologically exposed to 2–7% oxygen, and that key oxygen species such as H2O2 act as signaling messengers in such a hypoxic environment. Indeed, with the recently introduced glucose oxidase/catalase (GOX/CAT) system it has been possible to independently study hypoxia and H2O2 signaling. First preliminary data indicate that hypoxia enhances H2O2-mediated induction of hepcidin, pointing towards oxidases such as NADPH oxidase 4 (NOX4). We here review and discuss novel concepts of hypoxia signaling that could help to better understand hepcidin-associated iron overload in ALD. View Full-Text
Keywords: ALD; HCC; hepatic iron overload; hepcidin; hydrogen peroxide; hypoxia; GOX/CAT system; NOX4; oxidative stress ALD; HCC; hepatic iron overload; hepcidin; hydrogen peroxide; hypoxia; GOX/CAT system; NOX4; oxidative stress
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Silva, I.; Rausch, V.; Seitz, H.-K.; Mueller, S. Does Hypoxia Cause Carcinogenic Iron Accumulation in Alcoholic Liver Disease (ALD)? Cancers 2017, 9, 145.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top