Melatonin reduces the impairment of axonal transport and axonopathy induced by calyculin A

Previous studies have reported that calyculin A (CA), a selective inhibitor of protein phosphatase (PP)-2A and PP-1, impairs axonal transport in neuroblastoma N2a cells. Melatonin prevents Alzheimer-like hyperphosphorylation of cytoskeletal proteins and the impairment of spatial memory retention induced by CA. In this study, we tested the effects of melatonin on the impairment of axonal transport induced by CA in neuroblastoma N2a cells. We found that melatonin protected the cells from CA-induced toxicity in metabolism and viability as well as hyperphosphorylation of tau and neurofilaments. Furthermore, melatonin partially reversed the CA-induced phosphorylation of the catalytic subunit of PP-2A at tyrosine 307, a crucial site that negatively regulates the activity of PP-2A, and reduced the levels of malondialdehyde and the activity of superoxide dismutase, which are markers of oxidative stress. Melatonin also significantly reversed the CA-induced impairment of axonal transport. These results suggest that melatonin may have a role in protecting against the CA-induced impairment of axonal transport by modulating the activity of PP-2A and oxidative stress.