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*

*Corresponding author for this work

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

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