Fatty acid-mediated intracellular iron translocation: A synergistic mechanism of oxidative injury

Dachun Yao, Weibin Shi, Yulan Gou, Xinrong Zhou, Yee Aw Tak, Yikai Zhou, Zhengxiang Liu

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

Fatty acid has been reported to be associated with cardiovascular diseases and cancer, but the possible mechanism remains unclear. Here, we reported a novel mechanism for the permissive role of fatty acid on iron intracellular translocation and subsequent oxidative injury. In vitro study from endothelial cells showed that iron alone had little effect, whereas in combination with PA (palmitic acid), iron-mediated toxicity was markedly potentiated, as reflected in mitochondrial dysfunction, cell death, apoptosis, and DNA mutation. We also showed that PA not only facilitated iron translocation into cells through a transferrin-receptor (TfR)-independent mechanism, but also translocated iron into mitochondria; the subsequent intracellular iron overload resulted in reactive oxygen species (ROS) overgeneration and lipid oxidation. Further investigation revealed that PA-facilitated iron translocation is due to Fe/PA-mediated extracellular oxidative stress and the subsequent membrane damage with increased membrane permeability. Fe/PA-mediated toxic effects were reduced in ρ0 cells lacking mitochondrial DNA or by antioxidant enzyme SOD, especially mitochondrially localized MnSOD, suggesting a permissive role of PA for iron deposition on the vascular wall and its subsequent toxicity via mitochondrial oxidative stress. This observation was confirmed in vivo in mice, wherein higher vascular iron deposition and accompanying superoxide release were observed in the presence of a high-fat diet with iron administration.

Original languageEnglish (US)
Pages (from-to)1385-1398
Number of pages14
JournalFree Radical Biology and Medicine
Volume39
Issue number10
DOIs
StatePublished - Nov 15 2005

Fingerprint

Fatty Acids
Iron
Palmitic Acid
Wounds and Injuries
Oxidative stress
Blood Vessels
Oxidative Stress
Toxicity
Membranes
Transferrin Receptors
Iron Overload
Poisons
Mitochondria
High Fat Diet
Endothelial cells
Mitochondrial DNA
Superoxides
Cell death
Nutrition
Permeability

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology (medical)

Cite this

Yao, Dachun ; Shi, Weibin ; Gou, Yulan ; Zhou, Xinrong ; Tak, Yee Aw ; Zhou, Yikai ; Liu, Zhengxiang. / Fatty acid-mediated intracellular iron translocation : A synergistic mechanism of oxidative injury. In: Free Radical Biology and Medicine. 2005 ; Vol. 39, No. 10. pp. 1385-1398.
@article{5fa52e60c58d467897d15cc7de06b886,
title = "Fatty acid-mediated intracellular iron translocation: A synergistic mechanism of oxidative injury",
abstract = "Fatty acid has been reported to be associated with cardiovascular diseases and cancer, but the possible mechanism remains unclear. Here, we reported a novel mechanism for the permissive role of fatty acid on iron intracellular translocation and subsequent oxidative injury. In vitro study from endothelial cells showed that iron alone had little effect, whereas in combination with PA (palmitic acid), iron-mediated toxicity was markedly potentiated, as reflected in mitochondrial dysfunction, cell death, apoptosis, and DNA mutation. We also showed that PA not only facilitated iron translocation into cells through a transferrin-receptor (TfR)-independent mechanism, but also translocated iron into mitochondria; the subsequent intracellular iron overload resulted in reactive oxygen species (ROS) overgeneration and lipid oxidation. Further investigation revealed that PA-facilitated iron translocation is due to Fe/PA-mediated extracellular oxidative stress and the subsequent membrane damage with increased membrane permeability. Fe/PA-mediated toxic effects were reduced in ρ0 cells lacking mitochondrial DNA or by antioxidant enzyme SOD, especially mitochondrially localized MnSOD, suggesting a permissive role of PA for iron deposition on the vascular wall and its subsequent toxicity via mitochondrial oxidative stress. This observation was confirmed in vivo in mice, wherein higher vascular iron deposition and accompanying superoxide release were observed in the presence of a high-fat diet with iron administration.",
author = "Dachun Yao and Weibin Shi and Yulan Gou and Xinrong Zhou and Tak, {Yee Aw} and Yikai Zhou and Zhengxiang Liu",
year = "2005",
month = "11",
day = "15",
doi = "10.1016/j.freeradbiomed.2005.07.015",
language = "English (US)",
volume = "39",
pages = "1385--1398",
journal = "Free Radical Biology and Medicine",
issn = "0891-5849",
publisher = "Elsevier Inc.",
number = "10",

}

Fatty acid-mediated intracellular iron translocation : A synergistic mechanism of oxidative injury. / Yao, Dachun; Shi, Weibin; Gou, Yulan; Zhou, Xinrong; Tak, Yee Aw; Zhou, Yikai; Liu, Zhengxiang.

In: Free Radical Biology and Medicine, Vol. 39, No. 10, 15.11.2005, p. 1385-1398.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Fatty acid-mediated intracellular iron translocation

T2 - A synergistic mechanism of oxidative injury

AU - Yao, Dachun

AU - Shi, Weibin

AU - Gou, Yulan

AU - Zhou, Xinrong

AU - Tak, Yee Aw

AU - Zhou, Yikai

AU - Liu, Zhengxiang

PY - 2005/11/15

Y1 - 2005/11/15

N2 - Fatty acid has been reported to be associated with cardiovascular diseases and cancer, but the possible mechanism remains unclear. Here, we reported a novel mechanism for the permissive role of fatty acid on iron intracellular translocation and subsequent oxidative injury. In vitro study from endothelial cells showed that iron alone had little effect, whereas in combination with PA (palmitic acid), iron-mediated toxicity was markedly potentiated, as reflected in mitochondrial dysfunction, cell death, apoptosis, and DNA mutation. We also showed that PA not only facilitated iron translocation into cells through a transferrin-receptor (TfR)-independent mechanism, but also translocated iron into mitochondria; the subsequent intracellular iron overload resulted in reactive oxygen species (ROS) overgeneration and lipid oxidation. Further investigation revealed that PA-facilitated iron translocation is due to Fe/PA-mediated extracellular oxidative stress and the subsequent membrane damage with increased membrane permeability. Fe/PA-mediated toxic effects were reduced in ρ0 cells lacking mitochondrial DNA or by antioxidant enzyme SOD, especially mitochondrially localized MnSOD, suggesting a permissive role of PA for iron deposition on the vascular wall and its subsequent toxicity via mitochondrial oxidative stress. This observation was confirmed in vivo in mice, wherein higher vascular iron deposition and accompanying superoxide release were observed in the presence of a high-fat diet with iron administration.

AB - Fatty acid has been reported to be associated with cardiovascular diseases and cancer, but the possible mechanism remains unclear. Here, we reported a novel mechanism for the permissive role of fatty acid on iron intracellular translocation and subsequent oxidative injury. In vitro study from endothelial cells showed that iron alone had little effect, whereas in combination with PA (palmitic acid), iron-mediated toxicity was markedly potentiated, as reflected in mitochondrial dysfunction, cell death, apoptosis, and DNA mutation. We also showed that PA not only facilitated iron translocation into cells through a transferrin-receptor (TfR)-independent mechanism, but also translocated iron into mitochondria; the subsequent intracellular iron overload resulted in reactive oxygen species (ROS) overgeneration and lipid oxidation. Further investigation revealed that PA-facilitated iron translocation is due to Fe/PA-mediated extracellular oxidative stress and the subsequent membrane damage with increased membrane permeability. Fe/PA-mediated toxic effects were reduced in ρ0 cells lacking mitochondrial DNA or by antioxidant enzyme SOD, especially mitochondrially localized MnSOD, suggesting a permissive role of PA for iron deposition on the vascular wall and its subsequent toxicity via mitochondrial oxidative stress. This observation was confirmed in vivo in mice, wherein higher vascular iron deposition and accompanying superoxide release were observed in the presence of a high-fat diet with iron administration.

UR - http://www.scopus.com/inward/record.url?scp=27544495240&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27544495240&partnerID=8YFLogxK

U2 - 10.1016/j.freeradbiomed.2005.07.015

DO - 10.1016/j.freeradbiomed.2005.07.015

M3 - Article

C2 - 16257648

AN - SCOPUS:27544495240

VL - 39

SP - 1385

EP - 1398

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

SN - 0891-5849

IS - 10

ER -