β-adrenoceptor blockers protect against staurosporine-induced apoptosis in SH-SY5Y neuroblastoma cells

Mikami, Maya; Goubaeva, Farida; Song, Jing-Sheng; Lee, H.T.; Yang, Jay

doi:10.1016/j.ejphar.2008.04.045

Cited by 16 publications

(19 citation statements)

References 43 publications

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“…Indeed, SH-SY5Y cells express both β1- and β2-AR but not β3-AR (29). APPswe cells were treated using increasing concentrations of the β2-AR antagonist ICI (Fig.…”

Section: Resultsmentioning

confidence: 99%

Amyloid β production is regulated by β2-adrenergic signaling-mediated post-translational modifications of the ryanodine receptor

Bussiere

Lacampagne

Reiken

et al. 2017

Journal of Biological Chemistry

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Alteration of ryanodine receptor (RyR)-mediated calcium (Ca2+) signaling has been reported in Alzheimer disease (AD) models. However, the molecular mechanisms underlying altered RyR-mediated intracellular Ca2+ release in AD remain to be fully elucidated. We report here that RyR2 undergoes post-translational modifications (phosphorylation, oxidation, and nitrosylation) in SH-SY5Y neuroblastoma cells expressing the β-amyloid precursor protein (βAPP) harboring the familial double Swedish mutations (APPswe). RyR2 macromolecular complex remodeling, characterized by depletion of the regulatory protein calstabin2, resulted in increased cytosolic Ca2+ levels and mitochondrial oxidative stress. We also report a functional interplay between amyloid β (Aβ), β-adrenergic signaling, and altered Ca2+ signaling via leaky RyR2 channels. Thus, post-translational modifications of RyR occur downstream of Aβ through a β2-adrenergic signaling cascade that activates PKA. RyR2 remodeling in turn enhances βAPP processing. Importantly, pharmacological stabilization of the binding of calstabin2 to RyR2 channels, which prevents Ca2+ leakage, or blocking the β2-adrenergic signaling cascade reduced βAPP processing and the production of Aβ in APPswe-expressing SH-SY5Y cells. We conclude that targeting RyR-mediated Ca2+ leakage may be a therapeutic approach to treat AD.

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“…Indeed, SH-SY5Y cells express both β1- and β2-AR but not β3-AR (29). APPswe cells were treated using increasing concentrations of the β2-AR antagonist ICI (Fig.…”

Section: Resultsmentioning

confidence: 99%

Amyloid β production is regulated by β2-adrenergic signaling-mediated post-translational modifications of the ryanodine receptor

Bussiere

Lacampagne

Reiken

et al. 2017

Journal of Biological Chemistry

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“…Since differentiation agents were found to affect various signaling pathways, their application would probably influence the tauopathy induction [28], [29]. Thus, we established more organotypic-like spheroid cultures from all three cell lines (Fig.…”

Section: Resultsmentioning

confidence: 99%

Induced Tauopathy in a Novel 3D-Culture Model Mediates Neurodegenerative Processes: A Real-Time Study on Biochips

et al. 2012

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Tauopathies including Alzheimer’s disease represent one of the major health problems of aging population worldwide. Therefore, a better understanding of tau-dependent pathologies and consequently, tau-related intervention strategies is highly demanded. In recent years, several tau-focused therapies have been proposed with the aim to stop disease progression. However, to develop efficient active pharmaceutical ingredients for the broad treatment of Alzheimer’s disease patients, further improvements are necessary for understanding the detailed neurodegenerative processes as well as the mechanism and side effects of potential active pharmaceutical ingredients (API) in the neuronal system. In this context, there is a lack of suitable complex in vitro cell culture models recapitulating major aspects of taupathological degenerative processes in sufficient time and reproducible manner.Herewith, we describe a novel 3D SH-SY5Y cell-based, tauopathy model that shows advanced characteristics of matured neurons in comparison to monolayer cultures without the need of artificial differentiation promoting agents. Moreover, the recombinant expression of a novel highly pathologic fourfold mutated human tau variant lead to a fast and emphasized degeneration of neuritic processes. The neurodegenerative effects could be analyzed in real time and with high sensitivity using our unique microcavity array-based impedance spectroscopy measurement system. We were able to quantify a time- and concentration-dependent relative impedance decrease when Alzheimer’s disease-like tau pathology was induced in the neuronal 3D cell culture model. In combination with the collected optical information, the degenerative processes within each 3D-culture could be monitored and analyzed. More strikingly, tau-specific regenerative effects caused by tau-focused active pharmaceutical ingredients could be quantitatively monitored by impedance spectroscopy.Bringing together our novel complex 3D cell culture taupathology model and our microcavity array-based impedimetric measurement system, we provide a powerful tool for the label-free investigation of tau-related pathology processes as well as the high content analysis of potential active pharmaceutical ingredient candidates.

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“…When expressed, this vector yields two independent proteins, EGFP and the human SK1 protein fused with the HA tag. Lentivirus was produced by a triple transfection of CMV-SK1-pLL3.7 (10 g), pVSVG (Vesicular stomatitis virus G, Invitrogen; 7 g), and p⌬8.9 (from Dr. V. Parjs, MIT, MA; 5 g) as previously described (26). In brief, CMV-SK1-pLL3.7 and the two packaging vectors were cotransfected into 80 -90% confluent HEK-293FT cells in 10-cm tissue culture plates using 20 l of Lipofectamine 2000 (Invitrogen, Carlsbad, CA) in serum-free OptiMEM medium according to the manufacturer's recommendations.…”

Section: Methodsmentioning

confidence: 99%

Isoflurane via TGF-β1 release increases caveolae formation and organizes sphingosine kinase signaling in renal proximal tubules

Song

Kim

Park

et al. 2010

American Journal of Physiology-Renal Physiology

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We previously showed that the inhalational anesthetic isoflurane protects against renal proximal tubule necrosis via isoflurane-mediated stimulation and translocation of sphingosine kinase-1 (SK1) with subsequent synthesis of sphingosine-1-phosphate (S1P) in renal proximal tubule cells (Kim M, Kim M, Kim N, D'Agati VD, Emala CW Sr, Lee HT. Am J Physiol Renal Physiol 293: F1827-F1835, 2007). We also demonstrated that the anti-necrotic and anti-inflammatory effect of isoflurane is due in part to phosphatidylserine (PS) externalization and subsequent release of transforming growth factor-beta1 (TGF-beta1) (Lee HT, Kim M, Kim J, Kim N, Emala CW. Am J Nephrol 27: 416-424, 2007). In this study, we tested the hypothesis that isoflurane, via TGF-beta1 release, increases caveolae formation in the buoyant fraction of the cell membrane of human renal proximal tubule (HK-2) cells to organize SK1 and S1P signaling. To detect SK1 protein in the caveolae/caveolin fractions, we overexpressed human SK1 in HK-2 cells (SK1-HK-2). SK1-HK-2 cells exposed to isoflurane increased caveolae/caveolin formation in the buoyant membrane fractions which contained key signaling intermediates involved in isoflurane-mediated renal tubule protection, including S1P, SK1, ERK MAPK, and TGF-beta1 receptors. Furthermore, treating SK1-HK-2 cells with recombinant TGF-beta1 or PS liposome mixture increased caveolae formation, mimicking the effects of isoflurane. Conversely, TGF-beta1-neutralizing antibody blocked the increase in caveolae formation induced by isoflurane in SK1-HK-2 cells. The increase in SK1 activity in the caveolae-enriched fractions from isoflurane-treated nonlentivirus-infected HK-2 cells, while smaller in magnitude, was qualitatively similar to that found in the SK1-HK-2 cell line. Finally, isoflurane also increased caveolae formation in the kidneys of TGF-beta1 +/+ mice but not in TGF-beta1 +/- mice (mice with reduced levels of TGF-beta1). Our study demonstrates that isoflurane organizes several key cytoprotective signaling intermediates including TGF-beta1 receptors, SK1 and ERK, within the caveolae fraction of the plasma membrane. Our findings may help to unravel the cellular signaling pathways of volatile anesthetic-mediated renal protection and lead to new therapeutic applications of inhalational anesthetics during the perioperative period.

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β-adrenoceptor blockers protect against staurosporine-induced apoptosis in SH-SY5Y neuroblastoma cells

Cited by 16 publications

References 43 publications

Amyloid β production is regulated by β2-adrenergic signaling-mediated post-translational modifications of the ryanodine receptor

Amyloid β production is regulated by β2-adrenergic signaling-mediated post-translational modifications of the ryanodine receptor

Induced Tauopathy in a Novel 3D-Culture Model Mediates Neurodegenerative Processes: A Real-Time Study on Biochips

Isoflurane via TGF-β1 release increases caveolae formation and organizes sphingosine kinase signaling in renal proximal tubules

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