S-Glutathionylation of Keap1: A new role for glutathione S-transferase pi in neuronal protection

Andreia Neves Carvalho, Carla Marques, Rita C. Guedes, Margarida Castro-Caldas, Elsa Rodrigues, Jack Van Horssen, Maria João Gama

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Oxidative stress is a key pathological feature of Parkinson's disease (PD). Glutathione S-transferase pi (GSTP) is a neuroprotective antioxidant enzyme regulated at the transcriptional level by the antioxidant master regulator nuclear factor-erythroid 2-related factor 2 (Nrf2). Here, we show for the first time that upon MPTP-induced oxidative stress, GSTP potentiates S-glutathionylation of Kelch-like ECH-associated protein 1 (Keap1), an endogenous repressor of Nrf2, in vivo. S-glutathionylation of Keap1 leads to Nrf2 activation and subsequently increases expression of GSTP. This positive feedback regulatory loop represents a novel mechanism by which GSTP elicits antioxidant protection in the brain.

Original languageEnglish
Pages (from-to)1455-1466
Number of pages12
JournalFEBS Letters
Volume590
Issue number10
DOIs
Publication statusPublished - 1 May 2016

Cite this

Carvalho, A. N., Marques, C., Guedes, R. C., Castro-Caldas, M., Rodrigues, E., Van Horssen, J., & Gama, M. J. (2016). S-Glutathionylation of Keap1: A new role for glutathione S-transferase pi in neuronal protection. FEBS Letters, 590(10), 1455-1466. https://doi.org/10.1002/1873-3468.12177
Carvalho, Andreia Neves ; Marques, Carla ; Guedes, Rita C. ; Castro-Caldas, Margarida ; Rodrigues, Elsa ; Van Horssen, Jack ; Gama, Maria João. / S-Glutathionylation of Keap1 : A new role for glutathione S-transferase pi in neuronal protection. In: FEBS Letters. 2016 ; Vol. 590, No. 10. pp. 1455-1466.
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Carvalho, AN, Marques, C, Guedes, RC, Castro-Caldas, M, Rodrigues, E, Van Horssen, J & Gama, MJ 2016, 'S-Glutathionylation of Keap1: A new role for glutathione S-transferase pi in neuronal protection' FEBS Letters, vol. 590, no. 10, pp. 1455-1466. https://doi.org/10.1002/1873-3468.12177

S-Glutathionylation of Keap1 : A new role for glutathione S-transferase pi in neuronal protection. / Carvalho, Andreia Neves; Marques, Carla; Guedes, Rita C.; Castro-Caldas, Margarida; Rodrigues, Elsa; Van Horssen, Jack; Gama, Maria João.

In: FEBS Letters, Vol. 590, No. 10, 01.05.2016, p. 1455-1466.

Research output: Contribution to journalArticleAcademicpeer-review

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T2 - A new role for glutathione S-transferase pi in neuronal protection

AU - Carvalho, Andreia Neves

AU - Marques, Carla

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AU - Rodrigues, Elsa

AU - Van Horssen, Jack

AU - Gama, Maria João

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