In vitro 6-hydroxydopamine-induced neurotoxicity: New insights on NF κB modulation.

In vitro 6-hydroxydopamine-induced neurotoxicity: New insights on NFκB modulation. Toxicol In Vitro. 2019 Jun 24;: Authors: Iglesias González Pablo A, Conde Melisa A, Verónica GP, Uranga Romina M, Salvador Gabriela A Abstract Neuronal exposure to 6-hydroxydopamine (6-OHDA), a hydroxylated analog of dopamine, constitutes a very useful strategy for studying the molecular events associated with neuronal death in Parkinson's disease. 6-OHDA increases oxidant levels and impairs mitochondrial respiratory chain, thus promoting neuronal injury and death. Despite the extensive use of 6-OHDA in animal models, the exact molecular events triggered by this neurotoxicant at the neuronal level have not been yet fully understood. Human IMR-32 neuroblastoma cells exposed to increasing concentrations of 6-OHDA displayed high levels of reactive oxygen species and increased plasma membrane permeability with concomitant cell viability diminution. As part of the neuronal response to 6-OHDA exposure, the nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) p65 subunit was observed. NFκB nuclear localization was also accompanied by an increase of IκB phosphorylation as well as a rise in cyclooxygenase-2 (COX-2) and the prostaglandin receptor, EP4, mRNA levels. Even though the canonical pathways participating in the modulation of NFκB have been extensively described, here we tested the hypothesis that 6-OHDA-i...
Source: Toxicology in Vitro - Category: Toxicology Authors: Tags: Toxicol In Vitro Source Type: research