Activation of Wnt/β-catenin pathway by exogenous Wnt1 protects SH-SY5Y cells against 6-hydroxydopamine toxicity.
Wnt1, initially described as a modulator of embryonic development, has recently been discovered to exert cytoprotective effects in cellular models of several diseases, including Parkinson's disease (PD). We, therefore, examined the neuroprotective effects of exogenous Wnt1 on dopaminergic SH-SY5Y cells treated with 6-hydroxydopamine (6-OHDA). Here, we show that 10-500 μM 6-OHDA treatment decreased cell viability and increased lactate dehydrogenase (LDH) leakage. SH-SY5Y cells treated with 100 μM 6-OHDA for 24 h showed reduced Wnt/β-catenin activity, decreased mitochondrial transmembrane potential, elevated levels of reactive oxidative species (ROS) and phosphatidylserine (PS) extraversion, increased levels of Chop and Bip/GRP78 and reduced level of p-Akt (Ser473). In contrast, exogenous Wnt1 attenuated 6-OHDA-induced changes. These results suggest that activation of the Wnt/β-catenin pathway by exogenous Wnt1 protects against 6-OHDA-induced changes by restoring mitochondria and endoplasmic reticulum (ER) function.
Department of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, People's Republic of China.
Lei
L
Wei
Congcong
C
Sun
Ming
M
Lei
Guofei
G
Li
Li
L
Yi
Feifei
F
Luo
Yi
Y
Li
Li
L
Ding
Zhuolin
Z
Liu
Shaomin
S
Li
Pingyi
P
Xu
D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D059290:Dopaminergic Neurons / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D016627:Oxidopamine / Q000633:toxicity*; D010718:Phosphatidylserines / Q000032:analysis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051155:Wnt1 Protein / Q000378:metabolism* / Q000494:pharmacology
D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D010718:Phosphatidylserines; D017382:Reactive Oxygen Species; D051155:Wnt1 Protein; D051742:Transcription Factor CHOP; D016627:Oxidopamine; D007770:L-Lactate Dehydrogenase; D051057:Proto-Oncogene Proteins c-akt