Reactive oxygen species (ROS) mediate the effects of leucine on translation regulation and type I collagen production in hepatic stellate cells

María P. Pérez de Obanos, María J. López-Zabalza, Elena Arriazu, Teresa Modol, Jesús Prieto, María T. Herraiz, María J. Iraburu

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

The amino acid leucine causes an increase of collagen α1(I) synthesis in hepatic stellate cells through the activation of translational regulatory mechanisms and PI3K/Akt/mTOR and ERK signaling pathways. The aim of the present study was to evaluate the role played by reactive oxygen species on these effects. Intracellular reactive oxygen species levels were increased in hepatic stellate cells incubated with leucine 5 mM at early time points, and this effect was abolished by pretreatment with the antioxidant glutathione. Preincubation with glutathione also prevented 4E-BP1, eIF4E and Mnk-1 phosphorylation induced by leucine, as well as enhancement of procollagen α1(I) protein levels. Inhibitors for MEK-1 (PD98059), PI3K (wortmannin) or mTOR (rapamycin) did not affect leucine-induced reactive oxygen species production. However, preincubation with glutathione prevented ERK, Akt and mTOR phosphorylation caused by treatment with leucine. The mitochondrial electron chain inhibitor rotenone and the NADPH oxidase inhibitor apocynin prevented reactive oxygen species production caused by leucine. Leucine also induced an increased phosphorylation of IR/IGF-R that was abolished by pretreatment with either rotenone or apocynin. Therefore, leucine exerts on hepatic stellate cells a prooxidant action through NADPH oxidase and mitochondrial Reactive oxygen species production and these effects mediate the activation of IR/IGF-IR and signaling pathways, finally leading to changes in translational regulation of collagen synthesis.

Original languageEnglish
Pages (from-to)1681-1688
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1773
Issue number11
DOIs
StatePublished - Nov 2007
Externally publishedYes

Keywords

  • Hepatic stellate cells
  • Leucine
  • Oxidative stress
  • Translational regulation
  • Type I collagen

Fingerprint

Dive into the research topics of 'Reactive oxygen species (ROS) mediate the effects of leucine on translation regulation and type I collagen production in hepatic stellate cells'. Together they form a unique fingerprint.

Cite this