Oxidative Stress Induces Neuronal Death by Recruiting a Protease and Phosphatase-gated Mechanism

Sée, Violaine; Loeffler, Jean‐Philippe

doi:10.1074/jbc.m104988200

Cited by 73 publications

(11 citation statements)

References 62 publications

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“…3 A , one possible explanation for the decrease in cyclin D 1 expression is the profound steady-state decrease in MAPK phosphorylation, from c-RAF to CREB (55), that accompanied NOX1 knockdown. CREB plays a critical role in the regulation of cyclin D 1 expression (56) and is known to be regulated by oxidative stress (57, 58). …”

Section: Discussionmentioning

confidence: 99%

NADPH oxidase 1 supports proliferation of colon cancer cells by modulating reactive oxygen species-dependent signal transduction

Juhász

Markel²,

Gaur³

et al. 2017

Journal of Biological Chemistry

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Reactive oxygen species (ROS) play a critical role in cell signaling and proliferation. NADPH oxidase 1 (NOX1), a membrane-bound flavin dehydrogenase that generates O2˙̄, is highly expressed in colon cancer. To investigate the role that NOX1 plays in colon cancer growth, we used shRNA to decrease NOX1 expression stably in HT-29 human colon cancer cells. The 80–90% decrease in NOX1 expression achieved by RNAi produced a significant decline in ROS production and a G1/S block that translated into a 2–3-fold increase in tumor cell doubling time without increased apoptosis. The block at the G1/S checkpoint was associated with a significant decrease in cyclin D1 expression and profound inhibition of mitogen-activated protein kinase (MAPK) signaling. Decreased steady-state MAPK phosphorylation occurred concomitant with a significant increase in protein phosphatase activity for two colon cancer cell lines in which NOX1 expression was knocked down by RNAi. Diminished NOX1 expression also contributed to decreased growth, blood vessel density, and VEGF and hypoxia-inducible factor 1α (HIF-1α) expression in HT-29 xenografts initiated from NOX1 knockdown cells. Microarray analysis, supplemented by real-time PCR and Western blotting, revealed that the expression of critical regulators of cell proliferation and angiogenesis, including c-MYC, c-MYB, and VEGF, were down-regulated in association with a decline in hypoxic HIF-1α protein expression downstream of silenced NOX1 in both colon cancer cell lines and xenografts. These studies suggest a role for NOX1 in maintaining the proliferative phenotype of some colon cancers and the potential of NOX1 as a therapeutic target in this disease.

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Section: Discussionmentioning

confidence: 99%

NADPH oxidase 1 supports proliferation of colon cancer cells by modulating reactive oxygen species-dependent signal transduction

Juhász

Markel²,

Gaur³

et al. 2017

Journal of Biological Chemistry

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“…The neuroprotective effect of cotreatment with PP2B and calpain inhibitors against oxidative stress was reported by Sée and Loeffler (2001). To our knowledge, this is the first study showing that cotreatment with PP‐1/2A and calpain inhibitors rescues neuronal cells from OGD/reoxygenation‐induced cell death in vitro.…”

Section: Discussionmentioning

confidence: 56%

Dual inhibition of protein phosphatase‐1/2A and calpain rescues nerve growth factor‐differentiated PC12 cells from oxygen‐glucose deprivation‐induced cell death

Nakajima

Wakasa

Okuma

et al. 2005

J of Neuroscience Research

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In the present study, we examined how the cell survival signaling via cyclic AMP-responsive element binding protein (CREB) and Akt, and the cell death signaling via cystein proteases, calpain and caspase-3, are involved in oxygen-glucose deprivation (OGD) followed by reoxygenation (OGD/reoxygenation)-induced cell death in nerve growth factor (NGF)-differentiated PC12 cells. OGD/reoxygenation-induced cell death was evaluated by LDH release into the culture medium. The level of LDH release was low (9.0% +/- 4.1%) immediately after 4 hr of OGD (0 hr of reoxygenation), was significantly increased to 28.6% +/- 6.6% at 3 hr of reoxygenation, and remained at similar levels at 6 and 20 hr of reoxygenation, suggesting that reoxygenation at least for 3 hr resulted in the loss of cell membrane integrity. After 4 hr of OGD followed by 3 hr of reoxygenation, dephosphorylation of phosphorylated CREB (pCREB), but not phosphorylated Akt (pAkt), was induced. Under these conditions, calpain- but not caspase-3-mediated alpha-spectrin breakdown product was increased, indicating that OGD/reoxygenation also induced an increase in calpain activity. The restoration of pCREB by protein phosphatase (PP)-1/2A inhibitors or the inhibition of excessive activation of calpain by calpain inhibitor did not reduce OGD/reoxygenation-induced LDH release. Cotreatment with PP-1/2A and calpain inhibitors reduced OGD/reoxygenation-induced LDH release. The present study suggests that a balance in the phosphorylation and proteolytic signaling is involved in the survival of NGF-differentiated PC12 cells.

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“…CaMK4 and CREB are degraded by calpain, a calcium-dependent protease [78, 79]. Active calpain degraded CaMK4 and CREB in cultured neurons treated with hydrogen peroxide after CREB (P-S133) dephosphorylation [80]. Increased levels of calpain have been observed in in vitro and in vivo models of prion disease [81, 82], and calpain inhibition limited neuronal death in prion-infected cultured organotypic cerebellar slices or cultured neurons treated with PrP106-126 [81, 83, 84].…”

Section: Discussionmentioning

confidence: 99%

Activation of Pro-survival CaMK4β/CREB and Pro-death MST1 signaling at early and late times during a mouse model of prion disease

Shott

Majer

Frost

et al. 2014

Virol J

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BackgroundThe signaling pathways most critical to prion disease pathogenesis are as yet incompletely characterized. We have developed a kinomics approach to identify signaling pathways that are dysregulated during prion pathogenesis. The approach is sensitive and specific enough to detect signaling pathways dysregulated in a simple in vitro model of prion pathogenesis. Here, we used this approach to identify signaling pathways dysregulated during prion pathogenesis in vivo.MethodsMice intraperitoneally infected with scrapie (strain RML) were euthanized at 70, 90, 110, 130 days post-infection (dpi) or at terminal stages of disease (155–190 dpi). The levels of 139 protein kinases in brainstem-cerebellum homogenates were analyzed by multiplex Western blots, followed by hierarchical clustering and analyses of activation states.ResultsHierarchical and functional clustering identified CaMK4β and MST1 signaling pathways as potentially dysregulated. Targeted analyses revealed that CaMK4β and its downstream substrate CREB, which promotes neuronal survival, were activated at 70 and 90 dpi in cortical, subcortical and brainstem-cerebellum homogenates from scrapie-infected mice. The activation levels of CaMK4β/CREB signaling returned to those in mock-infected mice at 110 dpi, whereas MST1, which promotes neuronal death, became activated at 130 dpi.ConclusionPro-survival CaMK4β/CREB signaling is activated in mouse scrapie at earlier times and later inhibited, whereas pro-death MST1 signaling is activated at these later times.Electronic supplementary materialThe online version of this article (doi:10.1186/1743-422X-11-160) contains supplementary material, which is available to authorized users.

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Oxidative Stress Induces Neuronal Death by Recruiting a Protease and Phosphatase-gated Mechanism

Cited by 73 publications

References 62 publications

NADPH oxidase 1 supports proliferation of colon cancer cells by modulating reactive oxygen species-dependent signal transduction

NADPH oxidase 1 supports proliferation of colon cancer cells by modulating reactive oxygen species-dependent signal transduction

Dual inhibition of protein phosphatase‐1/2A and calpain rescues nerve growth factor‐differentiated PC12 cells from oxygen‐glucose deprivation‐induced cell death

Activation of Pro-survival CaMK4β/CREB and Pro-death MST1 signaling at early and late times during a mouse model of prion disease

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