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Open AccessArticle

Peroxiredoxin 6 Down-Regulation Induces Metabolic Remodeling and Cell Cycle Arrest in HepG2 Cells

1
Department of Biochemistry and Molecular Biology, University of Córdoba, 14074 Córdoba, Spain
2
Maimónides Biomedical Research Institute of Córdoba (IMIBIC), 14004 Córdoba, Spain
3
Department of Physiology, School of Medicine, NUI Galway, H91 TK33 Galway, Ireland
*
Author to whom correspondence should be addressed.
Antioxidants 2019, 8(11), 505; https://doi.org/10.3390/antiox8110505
Received: 27 September 2019 / Revised: 16 October 2019 / Accepted: 18 October 2019 / Published: 23 October 2019
(This article belongs to the Special Issue Peroxiredoxin)
Peroxiredoxin 6 (Prdx6) is the only member of 1-Cys subfamily of peroxiredoxins in human cells. It is the only Prdx acting on phospholipid hydroperoxides possessing two additional sites with phospholipase A2 (PLA2) and lysophosphatidylcholine-acyl transferase (LPCAT) activities. There are contrasting reports on the roles and mechanisms of multifunctional Prdx6 in several pathologies and on its sensitivity to, and influence on, the redox environment. We have down-regulated Prdx6 with specific siRNA in hepatoblastoma HepG2 cells to study its role in cell proliferation, redox homeostasis, and metabolic programming. Cell proliferation and cell number decreased while cell volume increased; import of glucose and nucleotide biosynthesis also diminished while polyamines, phospholipids, and most glycolipids increased. A proteomic quantitative analysis suggested changes in membrane arrangement and vesicle trafficking as well as redox changes in enzymes of carbon and glutathione metabolism, pentose-phosphate pathway, citrate cycle, fatty acid metabolism, biosynthesis of aminoacids, and Glycolysis/Gluconeogenesis. Specific redox changes in Hexokinase-2 (HK2), Prdx6, intracellular chloride ion channel-1 (CLIC1), PEP-carboxykinase-2 (PCK2), and 3-phosphoglycerate dehydrogenase (PHGDH) are compatible with the metabolic remodeling toward a predominant gluconeogenic flow from aminoacids with diversion at 3-phospohglycerate toward serine and other biosynthetic pathways thereon and with cell cycle arrest at G1/S transition. View Full-Text
Keywords: Peroxiredoxin; thiol redox regulation; redox proteome; redox homeostasis; lipid metabolism; cell cycle Peroxiredoxin; thiol redox regulation; redox proteome; redox homeostasis; lipid metabolism; cell cycle
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Grueso, M.J.L.; Valero, R.M.T.; Carmona, H.B.; Ruiz, D.J.L.; Peinado, J.; McDonagh, B.; Aguilar, R.R.; Ruiz, J.A.B.; Peña, C.A.P. Peroxiredoxin 6 Down-Regulation Induces Metabolic Remodeling and Cell Cycle Arrest in HepG2 Cells. Antioxidants 2019, 8, 505.

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