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Human embryonic stem cell derived astrocytes mediate non-cell-autonomous neuroprotection through endogenous and drug-induced mechanisms

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Human embryonic stem cell derived astrocytes mediate non-cell-autonomous neuroprotection through endogenous and drug-induced mechanisms. / Gupta, K.; Patani, R.; Baxter, P.; Serio, A.; Story, D.; Tsujita, T.; Hayes, J. D.; Pedersen, R. A.; Hardingham, G. E.; Chandran, S.

In: Cell Death & Differentiation, Vol. 19, No. 5, 05.2012, p. 779-787.

Research output: Contribution to journalArticle

Harvard

Gupta, K, Patani, R, Baxter, P, Serio, A, Story, D, Tsujita, T, Hayes, JD, Pedersen, RA, Hardingham, GE & Chandran, S 2012, 'Human embryonic stem cell derived astrocytes mediate non-cell-autonomous neuroprotection through endogenous and drug-induced mechanisms' Cell Death & Differentiation, vol 19, no. 5, pp. 779-787.

APA

Gupta, K., Patani, R., Baxter, P., Serio, A., Story, D., Tsujita, T., Hayes, J. D., Pedersen, R. A., Hardingham, G. E., & Chandran, S. (2012). Human embryonic stem cell derived astrocytes mediate non-cell-autonomous neuroprotection through endogenous and drug-induced mechanisms. Cell Death & Differentiation, 19(5), 779-787doi: 10.1038/cdd.2011.154

Vancouver

Gupta K, Patani R, Baxter P, Serio A, Story D, Tsujita T et al. Human embryonic stem cell derived astrocytes mediate non-cell-autonomous neuroprotection through endogenous and drug-induced mechanisms. Cell Death & Differentiation. 2012 May;19(5):779-787.

Author

Gupta, K.; Patani, R.; Baxter, P.; Serio, A.; Story, D.; Tsujita, T.; Hayes, J. D.; Pedersen, R. A.; Hardingham, G. E.; Chandran, S. / Human embryonic stem cell derived astrocytes mediate non-cell-autonomous neuroprotection through endogenous and drug-induced mechanisms.

In: Cell Death & Differentiation, Vol. 19, No. 5, 05.2012, p. 779-787.

Research output: Contribution to journalArticle

Bibtex - Download

@article{2fd91dd986354cebb82c99c4ec600b03,
title = "Human embryonic stem cell derived astrocytes mediate non-cell-autonomous neuroprotection through endogenous and drug-induced mechanisms",
author = "K. Gupta and R. Patani and P. Baxter and A. Serio and D. Story and T. Tsujita and Hayes, {J. D.} and Pedersen, {R. A.} and Hardingham, {G. E.} and S. Chandran",
year = "2012",
volume = "19",
number = "5",
pages = "779--787",
journal = "Cell Death & Differentiation",
issn = "1350-9047",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Human embryonic stem cell derived astrocytes mediate non-cell-autonomous neuroprotection through endogenous and drug-induced mechanisms

A1 - Gupta,K.

A1 - Patani,R.

A1 - Baxter,P.

A1 - Serio,A.

A1 - Story,D.

A1 - Tsujita,T.

A1 - Hayes,J. D.

A1 - Pedersen,R. A.

A1 - Hardingham,G. E.

A1 - Chandran,S.

AU - Gupta,K.

AU - Patani,R.

AU - Baxter,P.

AU - Serio,A.

AU - Story,D.

AU - Tsujita,T.

AU - Hayes,J. D.

AU - Pedersen,R. A.

AU - Hardingham,G. E.

AU - Chandran,S.

PY - 2012/5

Y1 - 2012/5

N2 - <p>The glial environment is an important determinant of neuronal health in experimental models of neurodegeneration. Specifically, astrocytes have been shown, dependent on context, to be both injurious and protective. Human pluripotent stem cells offer a powerful new system to improve our understanding of the mechanisms underlying astrocyte-mediated neuroprotection. Here, we describe a human embryonic stem cell (HESC)-based system to assess the scope and mechanism of human astrocyte-mediated neuroprotection. We first report the generation of enriched and functional HESC-derived astrocytes, by combining BMP-mediated Smad and LIF-mediated JAK-STAT signalling. These astrocytes promote the protection of HESC-derived neurons against oxidative insults. Moreover, their neuroprotective capacity can be greatly enhanced by treatment with the nuclear factor-erythroid 2-related factor 2 (Nrf2)-activating triterpenoid 1[2-Cyano-3,12-dioxool-eana-1,9(11)-dien-28-oyl] trifluoroethylamide (CDDOTFEA). Activation of the transcription factor Nrf2 in human astrocytes by CDDOTFEA treatment induced expression of the glutamate-cysteine ligase (GCL) catalytic subunit, leading to enhanced GCL activity and glutathione production, and strong neuroprotection against H2O2. This enhanced neuroprotection was found to be dependent on astrocytic GCL activity, unlike the basal neuroprotection afforded by untreated astrocytes. Direct treatment of HESC-derived neurons with CDDOTFEA elicited no induction of Nrf2 target genes, nor any neuroprotection. Thus, human astrocytes can mediate neuroprotection through glutathione-dependent and glutathione-independent mechanisms, and represent a therapeutic target for human disorders associated with neuronal oxidative stress. Cell Death and Differentiation (2012) 19, 779-787; doi:10.1038/cdd.2011.154; published online 18 November 2011</p>

AB - <p>The glial environment is an important determinant of neuronal health in experimental models of neurodegeneration. Specifically, astrocytes have been shown, dependent on context, to be both injurious and protective. Human pluripotent stem cells offer a powerful new system to improve our understanding of the mechanisms underlying astrocyte-mediated neuroprotection. Here, we describe a human embryonic stem cell (HESC)-based system to assess the scope and mechanism of human astrocyte-mediated neuroprotection. We first report the generation of enriched and functional HESC-derived astrocytes, by combining BMP-mediated Smad and LIF-mediated JAK-STAT signalling. These astrocytes promote the protection of HESC-derived neurons against oxidative insults. Moreover, their neuroprotective capacity can be greatly enhanced by treatment with the nuclear factor-erythroid 2-related factor 2 (Nrf2)-activating triterpenoid 1[2-Cyano-3,12-dioxool-eana-1,9(11)-dien-28-oyl] trifluoroethylamide (CDDOTFEA). Activation of the transcription factor Nrf2 in human astrocytes by CDDOTFEA treatment induced expression of the glutamate-cysteine ligase (GCL) catalytic subunit, leading to enhanced GCL activity and glutathione production, and strong neuroprotection against H2O2. This enhanced neuroprotection was found to be dependent on astrocytic GCL activity, unlike the basal neuroprotection afforded by untreated astrocytes. Direct treatment of HESC-derived neurons with CDDOTFEA elicited no induction of Nrf2 target genes, nor any neuroprotection. Thus, human astrocytes can mediate neuroprotection through glutathione-dependent and glutathione-independent mechanisms, and represent a therapeutic target for human disorders associated with neuronal oxidative stress. Cell Death and Differentiation (2012) 19, 779-787; doi:10.1038/cdd.2011.154; published online 18 November 2011</p>

U2 - 10.1038/cdd.2011.154

DO - 10.1038/cdd.2011.154

M1 - Article

JO - Cell Death & Differentiation

JF - Cell Death & Differentiation

SN - 1350-9047

IS - 5

VL - 19

SP - 779

EP - 787

ER -

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