Carnosic acid prevents 6-hydroxydopamine induced-apoptosis associated with modulation ARTS and XIAP by parkin in SH-SY5Y cells

Abstract

U the neuroprotective effects of carnosic acid (CA) from rosemary has attracted increasing attention in recent years. Parkin promotes the degradation of mitochondria pro-apoptotic ARTS (apoptosis-related protein in the TGF-β signaling pathway) protein and prevents it antagonizes XIAP (X-linked inhibitors of apoptosis proteins) leading to caspase activation. In this present study, we explored whether CA could prevent 6-hydroxydopamine (6-OHDA)-induced apoptosis via modulation of ARTS and XIAP by parkin in SH-SY5Y cells. The results showed that pretreatment cells with CA reduced 6-OHDA-induced the nuclear condensation and apoptotic proteins. Treatment cells with 6-OHDA increased ARTS protein and decreased XIAP protein as well as parkin protien. However, CA pretreatment reversed the effect by 6-OHDA. Performing immunoprecipitation using an antiARTS antibody, 6-OHDA increased the XIAP protein. In contrast, CA pretreatment reduced XIAP protein and increased ubiquitin protein in 6-OHDA treated cells. Silencing of XIAP reduced the CA inhibited 6-OHDA-increased the cleavage of caspase 9, 3, 7 and PARP. With parkin siRNA, CA reversed the 6-OHDA-induced ARTS and reduced XIAP was inhibited, which resulted in increasing apoptotic related proteins. In conclusion, CA protects SH-SY5Y cells against 6-OHDA-stimulated apoptosis via induction of parkin by enhancing the ubiquitination of ARTS, leading to induction of XIAP.