The effects of 3, 4 or 5 amino salicylic acids on manganese-induced neuronal death: ER stress and mitochondrial complexes

This study was designed to investigate the mechanisms that are associated with manganese (Mn) toxicity. In addition, the association between Mn toxicity and 3, 4, 5 amino salicylic acid (ASA), anti-oxidants, including N-acetyl cysteine (NAC), was examined by dopaminergic cell line, SK-M-NC. Our studies showed that Mn influenced the mitochondria dysfunction and endoplasmic reticulum stress (ER stress). It reduced the mitochondria complex I activity but did not affect the complex II, III, or IV activities. The presence of 3, 4, 5 ASA protected against Mn-induced-apoptosis, as did NAC. However, the salicylate analogues and the antioxidants did not mediate ER stress in this model. The salicylate analogues reduced reactive oxygen species (ROS) and reversed the deficient mitochondrial membrane potential that was induced by Mn. Taken together, the 3, 4, 5 ASA worked in a similar way, regulating the Mn-induced mitochondrial dysfunction and protecting cells.