How aluminum, an intracellular ROS generator promotes hepatic and neurological diseases: the metabolic tale
- 884 Downloads
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.
KeywordsAluminum toxicity Reactive oxygen species Mitochondrial dysfunction Dyslipidemia α-ketoacids Neurological and hepatic diseases
Electron transport chain
Reactive oxygen species
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.
- Adibhatla RM, Hatcher JF. Altered lipid metabolism in brain injury and disorders lipids in health and disease. In: Quinn PJ, Wang X, editors. Springer, Dordrecht; 2008.Google Scholar
- Bhasin P, Singla N, Dhawan DK. Protective role of zinc during aluminum-induced hepatotoxicity. Environ Toxicol. 2012. doi: 10.1002/tox.21760.
- Bignucolo A, Lemire J, Auger C, Castonguay Z, Appanna V, Appanna VD. The molecular connection between aluminum toxicity, anemia, inflammation and obesity: therapeutic cues. In: Silverberg DD, editor. Anemia: InTech; 2012.Google Scholar
- Kawahara M, Kato-Negishi M. Link between aluminum and the pathogenesis of Alzheimer's disease: the integration of the aluminum and Amyloid cascade hypothesis. Int J Alzheimer's Dis. 2011; 276393.Google Scholar
- Krewski D, Yokel RA, Nieboer E, Borchelt D, Cohen J, Harry J, et al. Human health risk assessment for aluminium, aluminium oxide, and aluminium hydroxide. J Toxicol Environ Health B. 2007;10:1–269.Google Scholar
- Lemire J. A global metabolic perspective on aluminum toxicity in human astrocytes: Implications for neurological disorders. Ph.D, Laurentian University; 2011.Google Scholar
- Li X, Han Y, Guan Y, Zhang L, Bai C & Li Y. Aluminum induces osteoblast apoptosis through the oxidative stress-mediated jnk signaling pathway. Biol Trace Elem Res. 2012; 1–7.Google Scholar
- Mallet RT, Sun J, Knott EM, Sharma AB, Olivencia-Yurvati AH. Metabolic cardioprotection by pyruvate: recent progress. Exp Biol Med. 2005;230:435–43.Google Scholar
- Middaugh J, Hamel R, Jean-Baptiste G, Beriault R, Chenier D, Appanna VD. Aluminum triggers decreased aconitase activity via Fe–S cluster disruption and the overexpression of isocitrate dehydrogenase and isocitrate lyase: a metabolic network mediating cellular survival. J Biol Chem. 2005;280:3159–65.PubMedCrossRefGoogle Scholar
- Praticò D, Uryu K, Sung S, Tang S, Trojanowski J. Q. & Lee V. M.-Y. Aluminum modulates brain amyloidosis through oxidative stress in APP transgenic mice. The FASEB Journal. 2002. 16, 1138–1140Google Scholar
- Reichenbach A, Wolburg H. Structural association of astrocytes with neurons and vasculature: defining territorial boundaries astrocytes in (patho)physiology of the nervous system. In: Haydon PG, Parpura V, editors. New York: Springer; 2009.Google Scholar
- Taylor JM, Main BS, Crack PJ. Neuroinflammation and oxidative stress: co-conspirators in the pathology of Parkinson's disease. Neurochem Int. 2013. doi: 10.1016/j.neuint.2012.12.016.