PTEN, Akt, and GSK3β signalling in rat primary cortical neuronal cultures following tumor necrosis factor‐α and trans‐4‐hydroxy‐2‐nonenal treatments

Rickle, Annika; Behbahani, Homira; Ankarcrona, Maria; Winblad, Bengt; Cowburn, Richard F.

doi:10.1002/jnr.20970

Cited by 17 publications

(9 citation statements)

References 36 publications

(39 reference statements)

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“…4-HNE can also be conjugated with GSH through Michael adduction 12. Results of our present study and of previous reports14,42,43 suggest that RPE cells use the Nrf2-dependent antioxidant system to detoxify 4-HNE.…”

Section: Discussionsupporting

confidence: 75%

Phosphatidylinositol 3 Kinase Pathway and 4-Hydroxy-2-Nonenal-Induced Oxidative Injury in the RPE

Chen

Sternberg

et al. 2009

Invest. Ophthalmol. Vis. Sci.

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Purpose 4-Hydroxy-2-nonenal (4-HNE) is a major lipid peroxidation product in the retina and the retinal pigment epithelium. The purpose of the present study was to investigate how NF-E2–related factor-2 (Nrf2) and phosphatidylinositol 3 (PI3K) pathways affect the responses of cultured human retinal pigment epithelial (RPE) cells to 4-HNE. Methods Cultured ARPE-19 cells were treated with different concentrations of 4-HNE and a PI3K inhibitor, LY294002. Intracellular glutathione (GSH) was measured by high-performance liquid chromatography (HPLC). The transcriptional activity of Nrf2 was measured by dual luciferase assay after transient transfection with reporter plasmids. The mRNA level of glutamate cysteine ligase (GCL) was quantified by real-time RT-PCR. Formation of HNE adduct on heat shock cognate protein 70 (Hsc70) was measured by immunoprecipitation and Western blot analyses. Results Treatment with 4-HNE increased Nrf2 activity and GSH synthesis in a dose-dependent manner in cultured RPE cells. The modulatory subunit of GCL was upregulated by 4-HNE. Antioxidant responses were largely abolished by pretreatment with LY294002. The modification of Hsc70 by 4-HNE was increased when PI3K was inhibited. Conclusions The Nrf2-dependent antioxidant response protects against 4-HNE toxicity, and this protective mechanism is dependent on the functions of the PI3K pathway.

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Section: Discussionsupporting

confidence: 75%

Phosphatidylinositol 3 Kinase Pathway and 4-Hydroxy-2-Nonenal-Induced Oxidative Injury in the RPE

Chen

Sternberg

et al. 2009

Invest. Ophthalmol. Vis. Sci.

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“…242 Consistently, HNE (5 mM) was found to induce early neuronal cell death. 243 On the contrary, using human neuroblastoma IRM-32 cells, Dozza et al 244 observed that treatment with 10 mM HNE provoked significant inhibition of the glycogen synthase kinase 3b, likely through the phosphorylation and activation of both Akt and ERK2; this HNEdependent effect was clearly abolished by cell co-treatment with LY294002 or U0126, inhibitors of the PI3K and ERK pathways, respectively. 244…”

Section: B Effect On the Serine/threonine Kinase Aktmentioning

confidence: 99%

4‐Hydroxynonenal: A membrane lipid oxidation product of medicinal interest

Poli

Schaur

Siems³

et al. 2007

Medicinal Research Reviews

389

411

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A comprehensive focus on 4-hydroxynonenal (HNE) as candidate molecule in a variety of pathophysiological conditions occurring in humans is here provided. Despite an active, now well characterized, metabolism in most cells and tissues, HNE can be easily detected and quantified by means of several methods, although with different sensitivity. Measurements of HNE and/or stable metabolites in biological fluids are already applied as lipid peroxidation/oxidative stress markers in a huge number of human disease processes, often sustained by inflammatory reactions. A primary involvement of this aldehydic product of membrane lipid oxidation in inflammation-related events, as well as in regulation of cell proliferation and growth, in necrotic or apoptotic cell death, appears supported by its marked ability to modulate several major pathways of cell signaling and, consequently, gene expression. The actual knowledge of HNE reactivity, metabolism, signaling and modulatory effect in the various human organs should provide a solid background to the investigation of the aldehyde's contribution to the pathogenesis of human major chronic diseases and would likely promote advanced and oriented applications not only in diagnosis and prevention but also in molecular treatment of human diseases.

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“…It has been reported that PTEN protein levels are reduced in AD brains accompanied by elevated Akt phosphorylation [106, 107, 108]. It was recently shown that S -nitrosylation of PTEN was markedly elevated in the brains in the early stages of AD [87].…”

Section: Contribution Of No and Protein S-nitrosylation In The Bramentioning

confidence: 99%

Protein S-nitrosylation: Role for nitric oxide signaling in neuronal death

Shahani

Sawa

2012

Biochimica et Biophysica Acta (BBA) - General Subjects

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One of the signaling mechanisms mediated by nitric oxide (NO) is through S-nitrosylation, the reversible redox-based modification of cysteine residues, on target proteins that regulate a myriad of physiological and pathophysiological processes. In particular, an increasing number of studies have identified important roles for S-nitrosylation in regulating cell death. These roles include double-edged effects dependent on the levels, spatiotemporal distribution, and origins of NO in the brain: in general S-nitrosylation resulting from the basal low level of NO in cells exerts anti-cell death effects, whereas S-nitrosylation elicited by induced NO upon stressed conditions is implicated in either pro-cell death effects or serves as a negative feedback mechanism and inhibits cell death. Furthermore, in addition to these cascades, mainly associated with apoptosis, massive levels of NO can lead to necrotic cell death. This review focuses on the proteins that are regulated by S-nitrosylation during cell death, in particular neuronal cell death and apoptosis. These mechanisms are involved in the pathogenesis of several diseases including degenerative diseases of the central nervous system (CNS).

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PTEN, Akt, and GSK3β signalling in rat primary cortical neuronal cultures following tumor necrosis factor‐α and trans‐4‐hydroxy‐2‐nonenal treatments

Cited by 17 publications

References 36 publications

Phosphatidylinositol 3 Kinase Pathway and 4-Hydroxy-2-Nonenal-Induced Oxidative Injury in the RPE

Phosphatidylinositol 3 Kinase Pathway and 4-Hydroxy-2-Nonenal-Induced Oxidative Injury in the RPE

4‐Hydroxynonenal: A membrane lipid oxidation product of medicinal interest

Protein S-nitrosylation: Role for nitric oxide signaling in neuronal death

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