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Glutathione S-Transferase pi Mediates MPTP-Induced c-Jun N-Terminal Kinase Activation in the Nigrostriatal Pathway

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Glutathione S-Transferase pi Mediates MPTP-Induced c-Jun N-Terminal Kinase Activation in the Nigrostriatal Pathway. / Castro-Caldas, M.; Carvalho, A.N.; Rodrigues, E.; Gama, M.J.; Henderson, C.; Wolf, C.R.

In: Molecular Neurobiology, 01.01.2012, p. 1-12.

Research output: Contribution to journalArticle

Harvard

Castro-Caldas, M, Carvalho, AN, Rodrigues, E, Gama, MJ, Henderson, C & Wolf, CR 2012, 'Glutathione S-Transferase pi Mediates MPTP-Induced c-Jun N-Terminal Kinase Activation in the Nigrostriatal Pathway' Molecular Neurobiology, pp. 1-12., 10.1007/s12035-012-8266-9

APA

Castro-Caldas, M., Carvalho, A. N., Rodrigues, E., Gama, M. J., Henderson, C., & Wolf, C. R. (2012). Glutathione S-Transferase pi Mediates MPTP-Induced c-Jun N-Terminal Kinase Activation in the Nigrostriatal Pathway. Molecular Neurobiology, 1-12. 10.1007/s12035-012-8266-9

Vancouver

Castro-Caldas M, Carvalho AN, Rodrigues E, Gama MJ, Henderson C, Wolf CR. Glutathione S-Transferase pi Mediates MPTP-Induced c-Jun N-Terminal Kinase Activation in the Nigrostriatal Pathway. Molecular Neurobiology. 2012 Jan 1;1-12. Available from: 10.1007/s12035-012-8266-9

Author

Castro-Caldas, M.; Carvalho, A.N.; Rodrigues, E.; Gama, M.J.; Henderson, C.; Wolf, C.R. / Glutathione S-Transferase pi Mediates MPTP-Induced c-Jun N-Terminal Kinase Activation in the Nigrostriatal Pathway.

In: Molecular Neurobiology, 01.01.2012, p. 1-12.

Research output: Contribution to journalArticle

Bibtex - Download

@article{262e1322073745c8aeb34d667581e848,
title = "Glutathione S-Transferase pi Mediates MPTP-Induced c-Jun N-Terminal Kinase Activation in the Nigrostriatal Pathway",
author = "M. Castro-Caldas and A.N. Carvalho and E. Rodrigues and M.J. Gama and C. Henderson and C.R. Wolf",
year = "2012",
doi = "10.1007/s12035-012-8266-9",
pages = "1--12",
journal = "Molecular Neurobiology",
issn = "0893-7648",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Glutathione S-Transferase pi Mediates MPTP-Induced c-Jun N-Terminal Kinase Activation in the Nigrostriatal Pathway

A1 - Castro-Caldas,M.

A1 - Carvalho,A.N.

A1 - Rodrigues,E.

A1 - Gama,M.J.

A1 - Henderson,C.

A1 - Wolf,C.R.

AU - Castro-Caldas,M.

AU - Carvalho,A.N.

AU - Rodrigues,E.

AU - Gama,M.J.

AU - Henderson,C.

AU - Wolf,C.R.

PY - 2012/1/1

Y1 - 2012/1/1

N2 - Parkinson's disease (PD) is a progressive movement disorder resulting from the death of dopaminergic neurons in the substantia nigra. Neurotoxin-based models of PD using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) recapitulate the neurological features of the disease, triggering a cascade of deleterious events through the activation of the c-Jun N-terminal kinase (JNK). The molecular mechanisms underlying the regulation of JNK activity under cellular stress conditions involve the activation of several upstream kinases along with the fine-tuning of different endogenous JNK repressors. Glutathione S-transferase pi (GSTP), a phase II detoxifying enzyme, has been shown to inhibit JNK-activated signaling by protein-protein interactions, preventing c-Jun phosphorylation and the subsequent trigger of the cell death cascade. Here, we use C57BL/6 wild-type and GSTP knockout mice treated with MPTP to evaluate the regulation of JNK signaling by GSTP in both the substantia nigra and the striatum. The results presented herein show that GSTP knockout mice are more susceptible to the neurotoxic effects of MPTP than their wild-type counterparts. Indeed, the administration of MPTP induces a progressive demise of nigral dopaminergic neurons together with the degeneration of striatal fibers at an earlier time-point in the GSTP knockout mice when compared to the wild-type mice. Also, MPTP treatment leads to increased p-JNK levels and JNK catalytic activity in both wild-type and GSTP knockout mice midbrain and striatum. Moreover, our results demonstrate that in vivo GSTP acts as an endogenous regulator of the MPTP-induced cellular stress response by controlling JNK activity through protein-protein interactions. © 2012 Springer Science+Business Media, LLC.

AB - Parkinson's disease (PD) is a progressive movement disorder resulting from the death of dopaminergic neurons in the substantia nigra. Neurotoxin-based models of PD using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) recapitulate the neurological features of the disease, triggering a cascade of deleterious events through the activation of the c-Jun N-terminal kinase (JNK). The molecular mechanisms underlying the regulation of JNK activity under cellular stress conditions involve the activation of several upstream kinases along with the fine-tuning of different endogenous JNK repressors. Glutathione S-transferase pi (GSTP), a phase II detoxifying enzyme, has been shown to inhibit JNK-activated signaling by protein-protein interactions, preventing c-Jun phosphorylation and the subsequent trigger of the cell death cascade. Here, we use C57BL/6 wild-type and GSTP knockout mice treated with MPTP to evaluate the regulation of JNK signaling by GSTP in both the substantia nigra and the striatum. The results presented herein show that GSTP knockout mice are more susceptible to the neurotoxic effects of MPTP than their wild-type counterparts. Indeed, the administration of MPTP induces a progressive demise of nigral dopaminergic neurons together with the degeneration of striatal fibers at an earlier time-point in the GSTP knockout mice when compared to the wild-type mice. Also, MPTP treatment leads to increased p-JNK levels and JNK catalytic activity in both wild-type and GSTP knockout mice midbrain and striatum. Moreover, our results demonstrate that in vivo GSTP acts as an endogenous regulator of the MPTP-induced cellular stress response by controlling JNK activity through protein-protein interactions. © 2012 Springer Science+Business Media, LLC.

UR - http://www.scopus.com/inward/record.url?scp=84860117545&partnerID=8YFLogxK

U2 - 10.1007/s12035-012-8266-9

DO - 10.1007/s12035-012-8266-9

M1 - Article

JO - Molecular Neurobiology

JF - Molecular Neurobiology

SN - 0893-7648

SP - 1

EP - 12

ER -

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