RT Journal Article
T1 Peroxiredoxin 6 Down-Regulation Induces Metabolic Remodeling and Cell Cycle Arrest in HepG2 Cells.
A1 López Grueso, María José
A1 Tarradas Valero, Rosa María
A1 Carmona-Hidalgo, Beatriz
A1 Lagal Ruiz, Daniel José
A1 Peinado, José
A1 McDonagh, Brian
A1 Requejo Aguilar, Raquel
A1 Bárcena Ruiz, José Antonio
A1 Padilla Peña, Carmen Alicia
K1 Peroxiredoxin
K1 cell cycle
K1 lipid metabolism
K1 redox homeostasis
K1 redox proteome
K1 thiol redox regulation
AB 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.
SN 2076-3921
YR 2019
FD 2019-10-23
LK https://hdl.handle.net/10668/26796
UL https://hdl.handle.net/10668/26796
LA en
DS RISalud
RD Apr 6, 2025