Redox survival signalling in retina-derived 661W cells

Mackey, Ashley; Sanvicens, Nuria; Groeger, Gillian; Doonan, Francesca; Wallace, Deborah; Cotter, Thomas G.

doi:10.1038/cdd.2008.43

Cited by 58 publications

(70 citation statements)

References 40 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In brain slices subjected to hypoxia, H 2 O 2 spares neurons from irreversible firing inhibition and induces neuroprotection (32,33). In retinal cells, H 2 O 2 -initiated AKT signaling is necessary to prevent apoptosis (34). Our current results expand the established protective effect of H 2 O 2 to show that enzymatic H 2 O 2 production in one cell-type (astrocytes) affords protection to a neighboring cell population (neurons).…”

Section: Discussionsupporting

confidence: 51%

Controlled enzymatic production of astrocytic hydrogen peroxide protects neurons from oxidative stress via an Nrf2-independent pathway

Haskew-Layton

Payappilly

Smirnova

et al. 2010

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

132

117

View full text Add to dashboard Cite

Neurons rely on their metabolic coupling with astrocytes to combat oxidative stress. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) appears important for astrocyte-dependent neuroprotection from oxidative insults. Indeed, Nrf2 activators are effective in stroke, Parkinson disease, and Huntington disease models. However, key endogenous signals that initiate adaptive neuroprotective cascades in astrocytes, including activation of Nrf2-mediated gene expression, remain unclear. Hydrogen peroxide (H 2 O 2 ) plays an important role in cell signaling and is an attractive candidate mediator of adaptive responses in astrocytes. Here we determine (i) the significance of H 2 O 2 in promoting astrocyte-dependent neuroprotection from oxidative stress, and (ii) the relevance of H 2 O 2 in inducing astrocytic Nrf2 activation. To control the duration and level of cytoplasmic H 2 O 2 production in astrocytes cocultured with neurons, we heterologously expressed the H 2 O 2 -producing enzyme Rhodotorula gracilis D-amino acid oxidase (rgDAAO) selectively in astrocytes. Exposure of rgDAAO-astrocytes to D-alanine lead to the concentration-dependent generation of H 2 O 2 . Seven hours of low-level H 2 O 2 production (∼3.7 nmol·min·mg protein) in astrocytes protected neurons from oxidative stress, but higher levels (∼130 nmol·min·mg protein) were neurotoxic. Neuroprotection occurred without direct neuronal exposure to astrocyte-derived H 2 O 2 , suggesting a mechanism specific to astrocytic intracellular signaling. Nrf2 activation mimicked the effect of astrocytic H 2 O 2 yet H 2 O 2 -induced protection was independent of Nrf2. Astrocytic protein tyrosine phosphatase inhibition also protected neurons from oxidative death, representing a plausible mechanism for H 2 O 2 -induced neuroprotection. These findings demonstrate the utility of rgDAAO for spatially and temporally controlling intracellular H 2 O 2 concentrations to uncover unique astrocyte-dependent neuroprotective mechanisms.

show abstract

Section: Discussionsupporting

confidence: 51%

Controlled enzymatic production of astrocytic hydrogen peroxide protects neurons from oxidative stress via an Nrf2-independent pathway

Haskew-Layton

Payappilly

Smirnova

et al. 2010

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

132

117

View full text Add to dashboard Cite

show abstract

“…PTEN, PP1a, PP2A, SHP-2 and PTP-1B were all found to be expressed (Figure 4a). The antibody used to detect PTEN is also described to be able to detect the oxidized form of PTEN 15 but we were unable to detect oxidized PTEN in the TonB.210 cells. Treatment of TonB.210 with calyculin A, which inhibits PP1a and PP2A activity, resulted in increased phosphorylation of Akt and GSK3b whereas treatment with okadaic acid, which inhibits PP2A activity but has little effect on PP1a activity at low concentrations, 23 had no effect on Akt and GSK3b phosphorylation (Figure 4b).…”

Section: Bcr-abl-induced Ros Exert Their Effects Through Inactivationmentioning

confidence: 56%

Bcr-Abl-mediated redox regulation of the PI3K/AKT pathway

et al. 2009

Self Cite

View full text Add to dashboard Cite

Bcr-Abl causes chronic myelogenous leukemia, a myeloproliferative disorder characterized by clonal expansion of hematopoietic progenitor cells. In this study, inducible expression of Bcr-Abl in TonB.210 cells is associated with increased production of intracellular reactive oxygen species (ROS), which is thought to play a role in survival signaling when generated at specific levels. Elevated ROS in Bcr-Abl-expressing cells were found to activate PI3k/Akt pathway members such as Akt and GSK3b as well as downstream targets b-catenin and Mcl-1. The activation of these proteins was inhibited by the flavoprotein inhibitor diphenyleneiodonium, which is commonly used to inhibit NADPH oxidase (Nox). This indicated that increased ROS might be related to increased activity of one member of the Nox family. Knock-down experiments using siRNA suggest that Nox-4 is the main source of increased ROS following Bcr-Abl expression. We showed that Bcr-Abl-induced ROS could also increase survival pathway signaling through redox inhibition of PP1a, a serine threonine phosphatase that negatively regulates the PI3k/Akt pathway. Overall our results demonstrate that Bcr-Abl expression increases Nox-4-generated ROS, which in turn increases survival signaling through PI3k/Akt pathway by inhibition of PP1a, thus contributing to the high level of resistance to apoptosis seen in these Bcr-Abl-expressing cells.

show abstract

“…This H 2 O 2 -induced prosurvival signaling pathway was also dependent on the oxidation and subsequent inhibition of the tumor suppressor PTEN (phosphatase and tensin homolog deleted from chromosome 10) (66,246). Similarly, in rat primary astrocytes, exogenous treatment with H 2 O 2 or application of hypoxia/reoxygenation triggered SHP-2 phosphorylation in a time-and dosedependent manner and led to its translocation into LRs, forming a complex with STAT-3 that activated downstream signaling molecules.…”

Section: Lr Redox Signaling Not Via Receptorsmentioning

confidence: 93%

Lipid Raft Redox Signaling: Molecular Mechanisms in Health and Disease

Jin

Zhang

Katirai

et al. 2011

Antioxidants & Redox Signaling

104

View full text Add to dashboard Cite

Lipid rafts, the sphingolipid and cholesterol-enriched membrane microdomains, are able to form different membrane macrodomains or platforms upon stimulations, including redox signaling platforms, which serve as a critical signaling mechanism to mediate or regulate cellular activities or functions. In particular, this raft platform formation provides an important driving force for the assembling of NADPH oxidase subunits and the recruitment of other related receptors, effectors, and regulatory components, resulting, in turn, in the activation of NADPH oxidase and downstream redox regulation of cell functions. This comprehensive review attempts to summarize all basic and advanced information about the formation, regulation, and functions of lipid raft redox signaling platforms as well as their physiological and pathophysiological relevance. Several molecular mechanisms involving the formation of lipid raft redox signaling platforms and the related therapeutic strategies targeting them are discussed. It is hoped that all information and thoughts included in this review could provide more comprehensive insights into the understanding of lipid raft redox signaling, in particular, of their molecular mechanisms, spatial-temporal regulations, and physiological, pathophysiological relevances to human health and diseases. Antioxid. Redox Signal. 15, 1043-1083.

show abstract

Redox survival signalling in retina-derived 661W cells

Cited by 58 publications

References 40 publications

Controlled enzymatic production of astrocytic hydrogen peroxide protects neurons from oxidative stress via an Nrf2-independent pathway

Controlled enzymatic production of astrocytic hydrogen peroxide protects neurons from oxidative stress via an Nrf2-independent pathway

Bcr-Abl-mediated redox regulation of the PI3K/AKT pathway

Lipid Raft Redox Signaling: Molecular Mechanisms in Health and Disease

Contact Info

Product

Resources

About