Wnt3a protects SH-SY5Y cells against 6-hydroxydopamine toxicity by restoration of mitochondria function

• Published in: Translational neurodegeneration Vol. 4; no. 1; p. 11
• Main Authors: Wei, Lei, Ding, Li, Mo, Ming-Shu, Lei, Ming, Zhang, Limin, Chen, Kang, Xu, Pingyi
• Format: Journal Article
• Language: English
• Published: England BioMed Central 16.06.2015
• Subjects: 6-OHDA; Mitochondria function; Wnt3a; Parkinson’s disease
• ISSN: 2047-9158; 2047-9158
• DOI: 10.1186/s40035-015-0033-1

Wnt/β-catenin signal has been reported to exert cytoprotective effects in cellular models of several diseases, including Parkinson's disease (PD). This study aimed to investigate the neuroprotective effects of actived Wnt/β-catenin signal by Wnt3a on SH-SY5Y cells treated with 6-hydroxydopamine (6-OHDA). Wnt3a-conditioned medium (Wnt3a-CM) was used to intervene dopaminegic SH-SY5Y cells treated with 6-OHDA. Cell toxicity was determined by cell viability and lactate dehydrogenase leakage (LDH) assay. The mitochondria function was measured by the mitochondrial membrane potential, while oxidative stress was monitored with intracellular reactive oxygen species (ROS). Western blot analysis was used to detect the expression of GSK3β, β-catenin as well as Akt. Our results showed that 100 μM 6-OHDA treated for 24 h significantly decreased cell viability and mitochondrial transmembrane potential, reduced the level of β-catenin and p-Akt, increased LDH leakage, ROS production and the ratio of p-GSK3β (Tyr216) to p-GSK3β (Ser9). However, Wnt3a-conditioned medium reversing SH-SY5Y cells against 6-OHDA-induced neurotoxicity by reversing these changes. Activating of Wnt/β-catenin pathway by Wnt3a-CM attenuated 6-OHDA-induced neurotoxicity significantly, which related to the inhibition of oxidative stress and maintenance of normal mitochondrial function.