REDOX proteomics reveals energy metabolism alterations in the liver of M. spretus mice exposed to p, p′-DDE

- p,p′-DDE exposure caused an impairment in liver redox homeostasis in M. spretus mice.
- Histological analysis showed hydropic degeneration of hepatocytes.
- p,p′-DDE exposure increased hepatic lipid peroxidation and the activity of glycolytic enzymes.
- The livers of p,p′-DDE-fed M. spretus mice lacked certain protective enzymes.
- p,p′-DDE shifts the liver metabolism towards aerobic glycolysis and FA accumulation.

The toxicity induced by the pesticide 2,2-bis(p-chlorophenyl)-1,1,1,-trichloroethane (DDT) and its derivative 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p′-DDE) has been associated with mitochondrial dysfunction, uncoupling of oxidative phosphorylation and respiratory chain electron transport, intracellular ion imbalance, generation of reactive oxygen species and impairment of the antioxidant defense system. A disruption in the cellular redox status causes protein Cys-based regulatory shifts that influence the activity of many proteins and trigger signal transduction alterations. Here, we analyzed the ability of p,p′-DDE to alter the activities of hepatic antioxidants and glycolytic enzymes to investigate the oxidative stress generation in the liver of p,p′-DDE-fed M. spretus mice. We also determined the consequences of the treatment on the redox status in the thiol Cys groups. The data indicate that the liver of p,p'-DDE exposed mice lacks certain protective enzymes, and p,p′-DDE caused a metabolic reprogramming that increased the glycolytic rate and disturbed the metabolism of lipids. Our results suggested that the overall metabolism of the liver was altered because important signaling pathways are controlled by p,p′-DDE-deregulated proteins. The histological data support the proposed metabolic consequences of the p,p′-DDE exposure.

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