Cytosolic Peroxiredoxin Attenuates The Activation Of Jnk And P38 But Potentiates That Of Erk In Hela Cells Stimulated With Tumor Necrosis Factor-α

Abstract

Tumor necrosis factor-␣ (TNF-␣

Reversible oxidation and inactivation of the tumor suppressor PTEN in cells stimulated with peptide growth factors

“…It was not possible to examine the effect of Prx II-DN by transient transfection because, in contrast to the situation in stably transfected cells, only a small fraction of the mutant protein molecules was able to form heterodimers with endogenous Prx II. Heterodimerization with endogenous enzyme molecules is the basis of the dominant negative action of the mutant protein (17). Together, these results suggested that PIP 3 accumulates to a greater extent and persists for a longer time in EGF-stimulated cells in which the intracellular concentration of H 2 O 2 is increased.…”

“…NIH 3T3 cells overexpressing human NADPH oxidase 1 (Nox1) were provided by J. D. Lambeth (Emory University School of Medicine, Atlanta) (16). HeLa cells overexpressing wild-type or a dominant negative mutant (DN) of human Prx II were described previously (17). HeLa and NIH 3T3 cells were grown under an atmosphere of 5% CO 2 at 37°C in DMEM supplemented with 10% FBS, 100 units͞ml penicillin, and 100 units͞ml streptomycin.…”

“…Prx II is a cytosolic Prx isoform and eliminates intracellular H 2 O 2 generated in response to cell stimulation with PDGF or EGF (23). We previously established and characterized HeLa cell lines that stably express wild-type (WT) or a DN of Prx II (17). The level of Prx II expression in these cell lines was about twice that in control cells transfected with the corresponding empty vector.…”

Sulfiredoxin is an AP-1 target gene that is required for transformation and shows elevated expression in human skin malignancies

“…Hyperoxidized Prxs have been reported to inhibit JNK activities either by removal of hydrogen peroxide (35), or by directly interacting with GSTpi-JNK complex (36). Therefore, Srx may positively regulate JNK activity by maintaining a constant level of reduced Prxs, facilitating the release and activation of JNK from the GSTpi-JNK complex (36).…”

Basic Principles and Emerging Concepts in the Redox Control of Transcription Factors

“…However, the idea that at least some of the GPx-or Prx-type peroxidases could similarly act as sensors for H 2 O 2 , alkyl hydroperoxides, and peroxynitrite in mammals is intriguing in several respects. It would comply with the observation that redox signaling also takes place at physiological H 2 O 2 fluxes; it could explain why in some cases Prxs improve rather than inhibit signaling (75,238), and it finally might help to explain oxidative modification of proteins with SH group reactivities that are simply not competitive enough to occur without enzymatic support (134). Mechanistically, transducing mechanisms analogous to those worked out for peroxidases of yeasts and Kinetoplastida would be straight forward for all 2-Cys Prxs.…”