A novel function of peroxiredoxin 1 (Prx‐1) in apoptosis signal‐regulating kinase 1 (ASK1)‐mediated signaling pathway

Kim, So Yong; Kim, Tae Jin; Lee, Ki-Young

doi:10.1016/j.febslet.2008.05.015

Cited by 118 publications

(98 citation statements)

References 21 publications

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“…We did not observe an increase in chondrocyte JNK phosphorylation in response to menadione-induced oxidative stress but rather found increased phosphorylation of MMK-3/6 and p38 along with inhibition of IGF-1-mediated Akt activation. This was consistent with previous studies demonstrating that PRX and thioredoxin can act as negative regulators of cell death pathways by direct inhibition of the ASK1-MKK3/6-p38 pathway in mice (49) and cell lines (50), an effect inhibited by oxidative stress. ROS-induced inhibition of Akt was also found to result in activation of the ASK1-MKK3/6-p38 pathway, which caused cell death in several cell lines (51).…”

Section: Discussionsupporting

confidence: 81%

Oxidative Stress Promotes Peroxiredoxin Hyperoxidation and Attenuates Pro-survival Signaling in Aging Chondrocytes

Collins

Wood

Nelson

et al. 2016

Journal of Biological Chemistry

114

122

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Oxidative stress-mediated post-translational modifications of redox-sensitive proteins are postulated as a key mechanism underlying age-related cellular dysfunction and disease progression. Peroxiredoxins (PRX) are critical intracellular antioxidants that also regulate redox signaling events. Age-related osteoarthritis is a common form of arthritis that has been associated with mitochondrial dysfunction and oxidative stress. The objective of this study was to determine the effect of aging and oxidative stress on chondrocyte intracellular signaling, with a specific focus on oxidation of cytosolic PRX2 and mitochondrial PRX3. Menadione was used as a model to induce cellular oxidative stress. Compared with chondrocytes isolated from young adult humans, chondrocytes from older adults exhibited higher levels of PRX1-3 hyperoxidation basally and under conditions of oxidative stress. Peroxiredoxin hyperoxidation was associated with inhibition of pro-survival Akt signaling and stimulation of pro-death p38 signaling. These changes were prevented in cultured human chondrocytes by adenoviral expression of catalase targeted to the mitochondria (MCAT) and in cartilage explants from MCAT transgenic mice. Peroxiredoxin hyperoxidation was observed in situ in human cartilage sections from older adults and in osteoarthritic cartilage. MCAT transgenic mice exhibited less age-related osteoarthritis. These findings demonstrate that age-related oxidative stress can disrupt normal physiological signaling and contribute to osteoarthritis and suggest peroxiredoxin hyperoxidation as a potential mechanism.Aging is characterized by an inability to maintain homeostasis resulting in a progressive loss of function and is associated with many chronic conditions including cancer, type II diabetes, neurodegenerative disease, cardiovascular disease, and osteoarthritis (1, 2). Although several theories aimed at explaining the aging phenotype have been suggested, an age-related imbalance between the production of reactive oxygen species (ROS) 2 and the antioxidant capacity of the cell has been identified as a contributing factor (3-5). Although the original free radical theory of aging focused on accumulation of cellular damage from excessive ROS as a cause for aging and age-related conditions, more recent studies suggest that disturbances in redox signaling that result from age-related oxidative stress are likely to play a key role (5-7). Increased levels of ROS caused by mitochondrial dysfunction, one of the hallmarks of aging, have been proposed to contribute to age-related oxidative stress, but the underlying mechanisms for how this increase causes a disruption in cell signaling leading to cell and tissue dysfunction is poorly understood (1, 4, 8).Recent advances in redox signaling recognize that reversible post-translational oxidative modifications of reactive protein cysteine thiols mediated by controlled production of H 2 O 2 regulate key signal transduction events (9, 10). The cysteine-dependent peroxiredoxins (PRXs), which display high rea...

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Section: Discussionsupporting

confidence: 81%

Oxidative Stress Promotes Peroxiredoxin Hyperoxidation and Attenuates Pro-survival Signaling in Aging Chondrocytes

Collins

Wood

Nelson

et al. 2016

Journal of Biological Chemistry

114

122

View full text Add to dashboard Cite

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“…Activated ASK1 phosphorylates MKK3/6, which, in turn, phosphorylates p38 MAPK (53). However, PRDX1 overexpression has also been reported to inhibit the phosphorylation of ASK1, MKK3/6, and p38 MAPK, although PRDX1 interacts with ASK1 via the thioredoxin-binding domain of the latter (55). PRDX1-mediated IL-12 production may be regulated by a pathway involving phosphatase and tensin homolog (PTEN) and PI3K, independent of c-Rel induction and p38 MAPK activation.…”

Section: Discussionmentioning

confidence: 99%

Peroxiredoxin 1 Contributes to Host Defenses against Mycobacterium tuberculosis

Matsumura

Iwai

Kato-Miyazawa

et al. 2016

The Journal of Immunology

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Peroxiredoxin (PRDX)1 is an antioxidant that detoxifies hydrogen peroxide and peroxinitrite. Compared with wild-type (WT) mice, Prdx1-deficient (Prdx1−/−) mice showed increased susceptibility to Mycobacterium tuberculosis and lower levels of IFN-γ and IFN-γ–producing CD4+ T cells in the lungs after M. tuberculosis infection. IL-12 production, c-Rel induction, and p38 MAPK activation levels were lower in Prdx1−/− than in WT bone marrow–derived macrophages (BMDMs). IFN-γ–activated Prdx1−/− BMDMs did not kill M. tubercuosis effectively. NO production levels were lower, and arginase activity and arginase 1 (Arg1) expression levels were higher, in IFN-γ–activated Prdx1−/− than in WT BMDMs after M. tuberculosis infection. An arginase inhibitor, Nω-hydroxy-nor-arginine, restored antimicrobial activity and NO production in IFN-γ–activated Prdx1−/− BMDMs after M. tuberculosis infection. These results suggest that PRDX1 contributes to host defenses against M. tuberculosis. PRDX1 positively regulates IL-12 production by inducing c-Rel and activating p38 MAPK, and it positively regulates NO production by suppressing Arg1 expression in macrophages infected with M. tuberculosis.

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“…ASK1 activity is regulated in multiple ways, one of which is through interaction with Prx1. The overexpression of Prx1 inhibits the activation of ASK1, and results in the inhibition of downstream signaling cascades such as the mitogen-activated protein kinase kinase 3/6 (MKK3/6), p38 and c-JNK pathway [25] . Moreover, overexpression of Prx1 could directly suppress IR-induced c-JNK activation and cell apoptosis through interaction with the glutathione S-transferase π (GSTπ)-JNK complex [26] .…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, overexpression of Prx1 could directly suppress IR-induced c-JNK activation and cell apoptosis through interaction with the glutathione S-transferase π (GSTπ)-JNK complex [26] . While, in Prx1 knock-down cells, ASK1, p38, and c-JNK are quickly activated, leading to cell apoptosis in response to H 2 O 2 [25] . The cell cycle phase also determines a cell's relative radiosensitivity, with cells being most radiosensitive in the G 2 -M phase, less sensitive in the G 1 phase, and least sensitive during the latter part of the S phase [27] .…”

Section: Discussionmentioning

confidence: 99%

Silencing Prx1 and/or Prx5 sensitizes human esophageal cancer cells to ionizing radiation and increases apoptosis via intracellular ROS accumulation

Gao

Jia

et al. 2011

Acta Pharmacol Sin

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Aim: To investigate whether down-regulation of peroxiredoxin 1 (Prx1) and/or peroxiredoxin 5 (Prx5) sensitizes human esophageal cancer cells to ionizing radiation (IR). Methods: Human esophageal carcinoma cell lines Eca-109 and TE-1 were used. Prx mRNA expression profiles in Eca-109 and TE-1 cells were determined using RT-PCR. Two highly expressed isoforms of Prxs, Prx1 and Prx5, were silenced by RNA interference (RNAi). Following IR, intracellular reactive oxygen species (ROS) and apoptosis were measured using flow cytometry, the activities of catalase, superoxide dismutase and glutathione peroxidase were measured, and the radiosensitizing effect of RNAi was observed. Tumor xenograft model was also used to examine the radiosensitizing effect of RNAi in vivo. Results: Down-regulation of Prx1 and/or Prx5 by RNAi does not alter the activities of catalase, superoxide dismutase and glutathione peroxidase, but made human tumor cells more sensitive to IR-induced apoptosis both in vitro and in vivo. When the two isoforms were decreased simultaneously, intracellular ROS and apoptosis significantly increased after IR. Conclusion: Silencing Prx1 and/or Prx5 by RNAi sensitizes human Eca-109 and TE-1 cells to IR, and the intracellular ROS accumulation may contribute to the radiosensitizing effect of the RNAi.

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A novel function of peroxiredoxin 1 (Prx‐1) in apoptosis signal‐regulating kinase 1 (ASK1)‐mediated signaling pathway

Cited by 118 publications

References 21 publications

Oxidative Stress Promotes Peroxiredoxin Hyperoxidation and Attenuates Pro-survival Signaling in Aging Chondrocytes

Oxidative Stress Promotes Peroxiredoxin Hyperoxidation and Attenuates Pro-survival Signaling in Aging Chondrocytes

Peroxiredoxin 1 Contributes to Host Defenses against Mycobacterium tuberculosis

Silencing Prx1 and/or Prx5 sensitizes human esophageal cancer cells to ionizing radiation and increases apoptosis via intracellular ROS accumulation

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