Hydrogen Peroxide Activates p70S6k Signaling Pathway

Bae, Gyu‐Un; Seo, Dong Wan; Kwon, Hyoung-Keun; Lee, Hoi Young; Hong, Sungyoul; Lee, Zee-Won; Ha, Kwon‐Soo; Lee, Hyang-Woo; Han, Jeung‐Whan

doi:10.1074/jbc.274.46.32596

Cited by 137 publications

(102 citation statements)

References 55 publications

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“…Redox events are involved in IL-1 signaling (15), and exogenous oxidants can activate the ERK1͞2 pathway (16,17). We therefore tested in HSVEC whether IL-1␣ induces the production of ROS, whether ROS mediate the expression of COX-2, which enzymes are involved in ROS generation, and finally whether DHA modulates this process.…”

Section: Dha Reduces the Production Of Intracellular Reactive Oxygen mentioning

confidence: 99%

The omega-3 fatty acid docosahexaenoate attenuates endothelial cyclooxygenase-2 induction through both NADP(H) oxidase and PKCε inhibition

Massaro

Habib

Lubrano

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

202

149

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A high intake of the omega-3 fatty acid docosahexaenoate [docosahexaenoic acid (DHA)] has been associated with systemic antiinflammatory effects and cardiovascular protection. Cyclooxygenase (COX)-2 is responsible for the overproduction of prostaglandins (PG) at inflammatory sites, and its expression is increased in atheroma. We studied the effects of DHA on COX-2 expression and activity in human saphenous vein endothelial cells challenged with proinflammatory stimuli. A ≥24-h exposure to DHA reduced COX-2 expression and activity induced by IL-1, without affecting COX-1 expression. DHA effect depended on the NF-κB-binding site in the COX-2 promoter. EMSAs confirmed that DHA attenuated NF-κB activation. Because MAPK, PKC, and NAD(P)H oxidase all participate in IL-1-mediated COX-2 expression, we also tested whether these enzymes were involved in DHA effects. Western blots showed that DHA blocked nuclear p65 NF-κB subunit translocation by decreasing cytokine-stimulated reactive oxygen species and ERK1/2 activation by effects on both NAD(P)H oxidase and PKCε activities. Finally, to address the question whether DHA itself or DHA-derived products were responsible for these effects, we inhibited the most important enzymes involved in polyunsaturated fatty acid metabolism, showing that 15-lipoxygenase-1 products mediate part of DHA effects. These studies provide a mechanistic basis for antiinflammatory and possibly plaque-stabilizing effects of DHA

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Section: Dha Reduces the Production Of Intracellular Reactive Oxygen mentioning

confidence: 99%

The omega-3 fatty acid docosahexaenoate attenuates endothelial cyclooxygenase-2 induction through both NADP(H) oxidase and PKCε inhibition

Massaro

Habib

Lubrano

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

202

149

View full text Add to dashboard Cite

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“…S6K activity upon H 2 O 2 treatment of cells is also dose-and time-dependent (Bae et al, 1999;Huang et al, 2002;Kim et al, 2002;Patel et al, 2002). Bae et al (1999) found that H 2 O 2 addition to mouse epidermal JB6 cells led to an initial rise in phospho-S6K signal within minutes, but dropped to background levels after 1 h (Bae et al, 1999). In another study, 1 mM H 2 O 2 addition for 10 min in HEK293T cells severely decreased mTOR activity with almost completely wiped out S6K phosphorylation .…”

Section: Ultraviolet and Rosmentioning

confidence: 97%

“…The activating effect can be attributed to the generation of reactive oxygen (ROS) species that accumulate in response to UV exposure, whereas pretreatment with ROS scavengers or antioxidants prevents S6K activation . S6K activity upon H 2 O 2 treatment of cells is also dose-and time-dependent (Bae et al, 1999;Huang et al, 2002;Kim et al, 2002;Patel et al, 2002). Bae et al (1999) found that H 2 O 2 addition to mouse epidermal JB6 cells led to an initial rise in phospho-S6K signal within minutes, but dropped to background levels after 1 h (Bae et al, 1999).…”

Section: Ultraviolet and Rosmentioning

confidence: 99%

Stress and mTORture signaling

2006

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“…Thus, ROS generated in a MAP17-dependent manner function as intracellular signals and induce a growth-related program. Accumulating evidence implicates ROS in signaling cascades related to cell proliferation and transformation (Fernandez-Pol et al, 1982;Church et al, 1993;Sundaresan et al, 1995;Burdon, 1996;Yan et al, 1996;Irani et al, 1997;Bae et al, 1999;Arnold et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

p38α limits the contribution of MAP17 to cancer progression in breast tumors

et al. 2012

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MAP17 is a small, 17-kDa, non-glycosylated membrane protein that is overexpressed in a percentage of carcinomas. In the present work, we have analyzed the role of MAP17 expression during mammary cancer progression. We have found that MAP17 is expressed in 60% human mammary tumors while it is not expressed in normal or benign neoplasias. MAP17 levels increased with breast tumor stage and were strongly correlated with mammary tumoral progression. A significant increase in the levels of reactive oxygen species (ROS) was observed in MAP17-expressing cells, as compared with parental cells. This increase was further paralleled by an increase in the tumorigenic capacity of carcinoma cells but not in immortal non-tumoral breast epithelial cells, which provides a selective advantage once tumorigenesis has begun. Expression of specific MAP17 shRNA in proteinexpressing tumor cells reduced their tumorigenic capabilities, which suggests that this effect is dependent upon MAP17 protein expression. Our data show that ROS functions as a second messenger that enhances tumoral properties, which are inhibited in non-tumoral cells. We have found that p38a activation mediates this response. MAP17 triggers a ROS-dependent, senescence-like response that is abolished in the absence of p38a activation. Furthermore, in human breast tumors, MAP17 activation is correlated with a lack of phosphorylation of p38a. Therefore, MAP17 is overexpressed in late-stage breast tumors, in which oncogenic activity relies on p38 insensitivity to induce intracellular ROS.

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Hydrogen Peroxide Activates p70S6k Signaling Pathway

Cited by 137 publications

References 55 publications

The omega-3 fatty acid docosahexaenoate attenuates endothelial cyclooxygenase-2 induction through both NADP(H) oxidase and PKCε inhibition

The omega-3 fatty acid docosahexaenoate attenuates endothelial cyclooxygenase-2 induction through both NADP(H) oxidase and PKCε inhibition

Stress and mTORture signaling

p38α limits the contribution of MAP17 to cancer progression in breast tumors

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