Quinolinic acid promotes the activation of Cullin3 and enhances Nrf2 ubiquitination in the nucleus of rat striatal cells

• DOI: 10.22533/at.ed.1593142327022

• Palavras-chave: -

• Keywords: QUINOLINIC ACID, CULLIN 3, NEDD8, NRF2, NEURODEGENERATION

• Abstract:

  Quinolinic acid (QUIN) is a neurotoxin that induces oxidative stress. The Nrf2- signaling pathway is a key player in the protection against oxidative stress, and is regulated by the interaction of Nrf2 with the Keap1 protein, which triggers Nrf2 degradation via the proteasome throughout Cullin3 (Cul3) ubiquitin ligase. In this paper, we show that QUIN induces nuclear expression of Cul3 and overexpression of its activator Nedd8 in both ex vivo and in vivo models, leading to the formation of Cul3-Keap1-Nrf2 complexes, with concomitant increase of Nrf2 ubiquitination. These results reveal the neddylation pathway as a key player on QUIN toxicity.