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The unravelling of metabolic dysfunctions linked to metal-associated diseases by blue native polyacrylamide gel electrophoresis

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Abstract

Gel electrophoresis is routinely used to separate and analyse macromolecules in biological systems. Although many of these electrophoretic techniques necessitate the denaturing of the analytes prior to their analysis, blue native polyacrylamide gel electrophoresis (BN-PAGE) permits the investigation of proteins/enzymes and their supramolecular structures such as the metabolon in native form. This attribute renders this analytical tool conducive to deciphering the metabolic perturbations invoked by metal toxicity. In this review, we elaborate on how BN-PAGE has led to the discovery of the dysfunctional metabolic pathways associated with disorders such as Alzheimer’s disease, Parkinson’s disease, and obesity that have been observed as a consequence of exposure to various metal toxicants.

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Abbreviations

ACC:

Acetyl coenzyme A carboxylase

BN buffer:

Blue native buffer

BN-PAGE:

Blue native polyacrylamide gel electrophoresis

ETC:

Electron transport chain

FAD:

Flavin adenine dinucleotide

Fe-S:

iron–sulfur

G6PDH:

Glucose 6-phosphate dehydrogenase

HK:

Hexokinase

ICDH:

Isocitrate dehydrogenase

INT:

Iodonitrotetrazolium chloride

NEIL:

Endonuclease VIII-like

PK:

Pyruvate kinase

PMS:

Phenazine methosulfate

ROS:

Reactive oxygen species

SDS-PAGE:

Sodium dodecyl sulfate polyacrylamide gel electrophoresis

TCA:

Tricarboxylic acid

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Acknowledgments

This work was supported by funding from Laurentian University and Industry Canada. C.A. is a recipient of a Natural Sciences and Engineering Research Council of Canada’s postgraduate scholarship at doctoral level.

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  1. Department of Chemistry and Biochemistry, Laurentian University, Sudbury, ON, P3E 2C6, Canada

    Sungwon Han, Christopher Auger, Zachary Castonguay, Varun P. Appanna, Sean C. Thomas & Vasu D. Appanna

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  1. Sungwon Han
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  2. Christopher Auger
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Correspondence to Vasu D. Appanna.

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Published in the topical collection Metallomics with guest editors Uwe Karst and Michael Sperling

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Han, S., Auger, C., Castonguay, Z. et al. The unravelling of metabolic dysfunctions linked to metal-associated diseases by blue native polyacrylamide gel electrophoresis. Anal Bioanal Chem 405, 1821–1831 (2013). https://doi.org/10.1007/s00216-012-6413-9

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