Albumin prevents reactive oxygen species-induced mitochondrial damage, autophagy, and apoptosis during serum starvation

Shu-Yu Liu, Chia-Ling Chen, Tsan-Tzu Yang, Wei-Ching Huang, Chia-Yuan Hsieh, Wan-Jou Shen, Tsung-Ting Tsai, Chi-Chang Shieh, Chiou Feng Lin

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Aberrant levels of reactive oxygen species (ROS) rapidly generated from NADPH oxidase (NOX) activation can be cytotoxic due to activating pro-apoptotic signals. However, ROS also induce pro-survival autophagy through the engulfment of damaged mitochondria. This study is aimed at investigating the cytoprotective role of albumin against NOX/ROS-induced autophagy and apoptosis under serum starvation. Serum starvation induced apoptosis following a myeloid cell leukemia sequence 1 (Mcl-1)/Bax imbalance, loss of the mitochondrial transmembrane potential, and caspase activation accompanied by pro-survival autophagy following canonical inhibition of mammalian target of rapamycin complex 1 (mTORC1). Aberrant ROS generation, initially occurring through NOX, facilitated mitochondrial damage, autophagy, and apoptosis. Autophagy additionally regulated the accumulation of ROS-generating mitochondria. NOX/ROS permitted p38 mitogen-activated protein kinase (p38 MAPK)-regulated mitochondrial apoptosis, accompanied by non-canonical induction of autophagy. In addition, activation of glycogen synthase kinase (GSK)-3β by NOX/ ROS-inactivated Akt facilitated a decrease in Mcl-1, followed by mitochondrial apoptosis as well as autophagy. Restoring albumin conferred an anti-oxidative effect against serum starvation-deregulated NOX, p38 MAPK, and Akt/GSK-3β/Mcl-1/caspase-3 signaling. Albumin also prevented autophagy by sustaining mTORC1. These results indicate an anti-oxidative role for albumin via preventing NOX/ROS-mediated mitochondrial signaling to stimulate apoptosis as well as autophagy. Autophagy, initially induced by canonical inhibition of mTORC1 and enhanced by non-canonical mitochondrial damage, acts physically as a pro-survival mechanism.

Original languageEnglish
Pages (from-to)1156-1169
Number of pages14
JournalApoptosis
Volume17
Issue number11
DOIs
Publication statusPublished - Nov 2012

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Keywords

  • Albumin
  • Apoptosis
  • Autophagy
  • GSK-3β
  • Mitochondria
  • NOX
  • p38 MAPK
  • ROS
  • Serum starvation

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Biochemistry, medical
  • Cancer Research
  • Pharmaceutical Science
  • Pharmacology

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