Fortilin potentiates the peroxidase activity of Peroxiredoxin-1 and protects against alcohol-induced liver damage in mice

Abhijnan Chattopadhyay, Decha Pinkaew, Hung Q. Doan, Reed B. Jacob, Sunil K. Verma, Hana Friedman, Alan C. Peterson, Neslihan Martinez, Owen M. McDougal, Kenichi Fujise

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Fortilin, a pro-survival molecule, inhibits p53-induced apoptosis by binding to the sequence-specific DNA-binding domain of the tumor suppressor protein and preventing it from transcriptionally activating Bax. Intriguingly, fortilin protects cells against ROS-induced cell death, independent of p53. The signaling pathway through which fortilin protects cells against ROS-induced cell death, however, is unknown. Here we report that fortilin physically interacts with the antioxidant enzyme peroxiredoxin-1 (PRX1), protects it from proteasome-mediated degradation, and keeps it enzymatically active by blocking its deactivating phosphorylation by Mst1, a serine/threonine kinase. At the whole animal level, the liver-specific overexpression of fortilin reduced PRX1 phosphorylation in the liver, enhanced PRX1 activity, and protected the transgenic animals against alcohol-induced, ROS-mediated, liver damage. These data suggest the presence of a novel oxidative-stress-handling pathway where the anti-p53 molecule fortilin augments the peroxidase PRX1 by protecting it against degradation and inactivation of the enzyme. Fortilin-PRX1 interaction in the liver could be clinically exploited further to prevent acute alcohol-induced liver damage in humans.

Original languageEnglish (US)
Article number18701
JournalScientific Reports
Volume6
DOIs
StatePublished - Jan 4 2016

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Peroxiredoxins
Peroxidase
Alcohols
Liver
Cell Death
Phosphorylation
Tumor Suppressor Proteins
Genetically Modified Animals
Protein-Serine-Threonine Kinases
Proteasome Endopeptidase Complex
Enzymes
Oxidative Stress
Antioxidants
Apoptosis
Survival

ASJC Scopus subject areas

  • General

Cite this

Fortilin potentiates the peroxidase activity of Peroxiredoxin-1 and protects against alcohol-induced liver damage in mice. / Chattopadhyay, Abhijnan; Pinkaew, Decha; Doan, Hung Q.; Jacob, Reed B.; Verma, Sunil K.; Friedman, Hana; Peterson, Alan C.; Martinez, Neslihan; McDougal, Owen M.; Fujise, Kenichi.

In: Scientific Reports, Vol. 6, 18701, 04.01.2016.

Research output: Contribution to journalArticle

Chattopadhyay, Abhijnan ; Pinkaew, Decha ; Doan, Hung Q. ; Jacob, Reed B. ; Verma, Sunil K. ; Friedman, Hana ; Peterson, Alan C. ; Martinez, Neslihan ; McDougal, Owen M. ; Fujise, Kenichi. / Fortilin potentiates the peroxidase activity of Peroxiredoxin-1 and protects against alcohol-induced liver damage in mice. In: Scientific Reports. 2016 ; Vol. 6.
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AU - Fujise, Kenichi

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