Format

Send to

Choose Destination
See comment in PubMed Commons below
FEBS Lett. 2014 Jan 3;588(1):175-83. doi: 10.1016/j.febslet.2013.11.033. Epub 2013 Dec 4.

TNF-α mediates mitochondrial uncoupling and enhances ROS-dependent cell migration via NF-κB activation in liver cells.

Author information

1
Division of Immunogenetics, Tumour Immunology Program, German Cancer Research Center (DKFZ), Heidelberg, Germany.
2
Department of General Pediatrics, Division of Inborn Metabolic Diseases, University Children's Hospital, Heidelberg, Germany.
3
Department of Medical Statistics, University of Goettingen, Goettingen, Germany.
4
Division of Immunogenetics, Tumour Immunology Program, German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: k.guelow@dkfz.de.

Abstract

Development of hepatocellular carcinoma (HCC) is accompanied by a continuous increase in reactive oxygen species (ROS) levels. To investigate the primary source of ROS in liver cells, we used tumor necrosis factor-alpha (TNF-α) as stimulus. Applying inhibitors against the respiratory chain complexes, we identified mitochondria as primary source of ROS production. TNF-α altered mitochondrial integrity by mimicking a mild uncoupling effect in liver cells, as indicated by a 40% reduction in membrane potential and ATP depletion (35%). TNF-α-induced ROS production activated NF-κB 3.5-fold and subsequently enhanced migration up to 12.7-fold. This study identifies complex I and complex III of the mitochondrial respiratory chain as point of release of ROS upon TNF-α stimulation of liver cells, which enhances cell migration by activating NF-κB signalling.

KEYWORDS:

CCCP; H(2)DCF-DA; HBV; HCV; Hepatocellular carcinoma (HCC); Hepatocytes; Liver cancer; Mitochondria; N-acetylcysteine; NAC; NF-κB; ROS; Reactive oxygen species (ROS); TMRE; TNF-α; carbonyl cyanide m-chlorophenyl hydrazine; dichlorofluorescein diacetate; hepatitis B virus; hepatitis C virus; reactive oxygen species; tetramethylrhodamine ethyl ester; tumor necrosis factor-alpha

PMID:
24316229
DOI:
10.1016/j.febslet.2013.11.033
[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley
    Loading ...
    Support Center