S-Glutathionylation of Keap1: a new role for glutathione S-transferase pi in neuronal protection.
Andreia Neves CarvalhoCarla MarquesRita C GuedesMargarida Castro-CaldasElsa RodriguesJack van HorssenMaria João GamaPublished in: FEBS letters (2016)
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.
Keyphrases
- oxidative stress
- transcription factor
- nuclear factor
- diabetic rats
- cerebral ischemia
- ischemia reperfusion injury
- dna damage
- protein protein
- induced apoptosis
- toll like receptor
- poor prognosis
- heat shock
- machine learning
- gene expression
- hydrogen peroxide
- white matter
- small molecule
- subarachnoid hemorrhage
- nitric oxide
- resting state
- long non coding rna
- immune response