Cell Biology and Toxicology

, Volume 29, Issue 2, pp 75–84 | Cite as

How aluminum, an intracellular ROS generator promotes hepatic and neurological diseases: the metabolic tale

  • Sungwon Han
  • Joseph Lemire
  • Varun P. Appanna
  • Christopher Auger
  • Zachary Castonguay
  • Vasu D. Appanna
Review Article

Abstract

Metal pollutants are a global health risk due to their ability to contribute to a variety of diseases. Aluminum (Al), a ubiquitous environmental contaminant is implicated in anemia, osteomalacia, hepatic disorder, and neurological disorder. In this review, we outline how this intracellular generator of reactive oxygen species (ROS) triggers a metabolic shift towards lipogenesis in astrocytes and hepatocytes. This Al-evoked phenomenon is coupled to diminished mitochondrial activity, anerobiosis, and the channeling of α-ketoacids towards anti-oxidant defense. The resulting metabolic reconfiguration leads to fat accumulation and a reduction in ATP synthesis, characteristics that are common to numerous medical disorders. Hence, the ability of Al toxicity to create an oxidative environment promotes dysfunctional metabolic processes in astrocytes and hepatocytes. These molecular events triggered by Al-induced ROS production are the potential mediators of brain and liver disorders.

Keywords

Aluminum toxicity Reactive oxygen species Mitochondrial dysfunction Dyslipidemia α-ketoacids Neurological and hepatic diseases 

Abbreviations

BADH

Betaine-aldehyde dehydrogenase

BBDOX

γ-butyrobetaine dioxygenase

ETC

Electron transport chain

HDL

High-density lipoprotein

HIF

Hypoxia-inducible factor

HTML

3-hydroxy-N6-trimethyllysine

ICDH

Isocitrate dehydrogenase

KGDH

Alpha-ketoglutarate dehydrogenase

LDL

Low-density lipoprotein

MDH

Malate dehydrogenase

PHD

Prolyl hydroxylase

ROS

Reactive oxygen species

TCA

Tricarboxylic acid

TML

N6-trimethyllysine

TMLD

Trimethyllysine dioxygenase

VLDL

Very-low-density lipoprotein

Notes

Acknowledgments

This work was supported by the Laurentian University and Industry Canada. Joseph Lemire was a recipient of the Alexander Graham Bell Canadian Graduate Scholarship (NSERC) and currently holds an NSERC-PDF, Christopher Auger is a recipient of the NSERC PGS-D.

Declaration of interest

The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.

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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Sungwon Han
    • 1
  • Joseph Lemire
    • 2
  • Varun P. Appanna
    • 1
  • Christopher Auger
    • 1
  • Zachary Castonguay
    • 1
  • Vasu D. Appanna
    • 1
  1. 1.Department of Chemistry and BiochemistryLaurentian UniversitySudburyCanada
  2. 2.Department of Biological SciencesUniversity of CalgaryCalgaryCanada

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