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

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.

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Abbreviations

BADH:

Betaine-aldehyde dehydrogenase

BBDOX:

γ-butyrobetaine dioxygenase

ETC:

Electron transport chain

HDL:

High-density lipoprotein

HIF:

Hypoxia-inducible factor

HTML:

3-hydroxy-N 6-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:

N 6-trimethyllysine

TMLD:

Trimethyllysine dioxygenase

VLDL:

Very-low-density lipoprotein

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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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Correspondence to Vasu D. Appanna.

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Han, S., Lemire, J., Appanna, V.P. et al. How aluminum, an intracellular ROS generator promotes hepatic and neurological diseases: the metabolic tale. Cell Biol Toxicol 29, 75–84 (2013). https://doi.org/10.1007/s10565-013-9239-0

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Keywords

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