TNF‐α mediates mitochondrial uncoupling and enhances ROS‐dependent cell migration via NF‐κB activation in liver cells. Issue 1 (4th December 2013)

• Record Type: Journal Article
• Authors: Kastl, L.; Sauer, S.W.; Ruppert, T.; Beissbarth, T.; Becker, M.S.; Süss, D.; Krammer, P.H.; Gülow, K.
• Is Part Of: FEBS letters. Volume 588:Issue 1(2014)
• Page Start: 175
• Page End: 183
• Publication Date: 2013-12-04
• Subjects: CCCP -- carbonyl cyanide m-chlorophenyl hydrazine -- HBV -- hepatitis B virus -- HCV -- hepatitis C virus -- H2DCF-DA -- dichlorofluorescein diacetate -- NAC -- N-acetylcysteine -- ROS -- reactive oxygen species -- TMRE -- tetramethylrhodamine ethyl ester -- TNF-α -- tumor necrosis factor-alpha -- Hepatocellular carcinoma (HCC) -- Hepatocytes -- Liver cancer -- Mitochondria -- NF-κB -- Reactive oxygen species (ROS) -- TNF-α; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2013.11.033
• Languages: English
• ISSNs: 0014-5793

Abstract

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. Abstract : TNF‐α induces mitochondrial ROS production in liver cells. ROS release involves complex I and/or complex III in liver cells. TNF‐α acts as mild uncoupler of mitochondria in liver cells. TNF‐α‐induced ROS production activates NF‐κB and enhances liver cell migration.