title: Phospholipase A(2) of peroxiredoxin 6 has a critical role in tumor necrosis factor-induced apoptosis.
abstract: Peroxiredoxin 6 (Prdx6) is a bifunctional enzyme with peroxidase and phospholipase A(2) (PLA(2)) activities. Although the cellular function of the peroxidase of Prdx6 has been well elucidated, the function of the PLA(2) of Prdx6 is largely unknown. Here, we report a novel function for the PLA(2) in regulating TNF-induced apoptosis through arachidonic acid (AA) release and interleukin-1β (IL-1β) production. Prdx6 knockdown (Prdx6(KD)) in human bronchial epithelial cells (BEAS2B) shows severe decreases of peroxidase and PLA(2) activities. Surprisingly, Prdx6(KD) cells are markedly resistant to apoptosis induced by TNF-α in the presence of cycloheximide, but are highly sensitive to hydrogen peroxide-induced apoptosis. Furthermore, the release of AA and the production of IL-1β induced by proinflammatory stimuli, such as TNF-α, LPS, and poly I/C, are severely decreased in Prdx6(KD) cells. More interestingly, the restoration of Prdx6 expression with wild-type Prdx6, but not PLA(2)-mutant Prdx6 (S32A), in Prdx6(KD) cells dramatically induces the recovery of TNF-induced apoptosis, AA release, and IL-1β production, indicating specific roles for the PLA(2) activity of Prdx6. Our results provide new insights into the distinct roles of bifunctional Prdx6 with peroxidase and PLA(2) activities in oxidative stress-induced and TNF-induced apoptosis, respectively.
authors.affiliation: Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Korea.
authors.forename: S Y
authors.initials: SY
authors.lastname: Kim
authors.forename: E
authors.initials: E
authors.lastname: Chun
authors.forename: K-Y
authors.initials: KY
authors.lastname: Lee
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D016718:Arachidonic Acid / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D053938:DNA Fragmentation / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D054465:Peroxiredoxin VI / Q000235:genetics / Q000378:metabolism*; D054467:Phospholipases A2 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016718:Arachidonic Acid; D054465:Peroxiredoxin VI; D054467:Phospholipases A2; D053148:Caspase 3; D053181:Caspase 8