First Author | Carvalho AN | Year | 2016 |
Journal | FEBS Lett | Volume | 590 |
Issue | 10 | Pages | 1455-66 |
PubMed ID | 27086966 | Mgi Jnum | J:233693 |
Mgi Id | MGI:5787865 | Doi | 10.1002/1873-3468.12177 |
Citation | Carvalho AN, et al. (2016) S-Glutathionylation of Keap1: a new role for glutathione S-transferase pi in neuronal protection. FEBS Lett 590(10):1455-66 |
abstractText | 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. |