ABSTRACT
Amyloid-ß (Aß), a primary component of amyloid plaques, has been widely associated with the pathogenesis of Alzheimer's disease. The Ca2+-binding protein regucalcin (RGN) plays multiple roles in maintaining cell functions by regulating intracellular calcium homeostasis, various signaling pathways, and gene expression systems. Here, we investigated the functional role of RGN against Aß-induced cytotoxicity in neuronally differentiated PC12 cells. Overexpression of RGN reduced Aß-induced apoptosis by reducing mitochondrial dysfunction and caspase activation. It also attenuated Aß-induced reactive oxygen species production and oxidative damage and decreased Aß-induced nitric oxide (NO) overproduction, upregulation of inducible NO synthase by nuclear factor-κB, and nitrosative damage. Interestingly, the genetic disruption of RGN increased the susceptibility of neuronally differentiated PC12 cells to Aß toxicity. Thus, RGN possesses antioxidant activity against Aß-induced oxidative and nitrosative stress and may play protective roles against Aß-induced neurotoxicity in Alzheimer's disease.