Necrostatin-1 protection of dopaminergic neurons.
Necroptosis is characterized by programmed necrotic cell death and autophagic activation and might be involved in the death process of dopaminergic neurons in Parkinson's disease. We hypothesized that necrostatin-1 could block necroptosis and give protection to dopaminergic neurons. There is likely to be crosstalk between necroptosis and other cell death pathways, such as apoptosis and autophagy. PC12 cells were pretreated with necroststin-1 1 hour before exposure to 6-hydroxydopamine. We examined cell viability, mitochondrial membrane potential and expression patterns of apoptotic and necroptotic death signaling proteins. The results showed that the autophagy/lysosomal pathway is involved in the 6-hydroxydopamine-induced death process of PC12 cells. Mitochondrial disability induced overactive autophagy, increased cathepsin B expression, and diminished Bcl-2 expression. Necrostatin-1 within a certain concentration range (5-30 μM) elevated the viability of PC12 cells, stabilized mitochondrial membrane potential, inhibited excessive autophagy, reduced the expression of LC3-II and cathepsin B, and increased Bcl-2 expression. These findings suggest that necrostatin-1 exerted a protective effect against injury on dopaminergic neurons. Necrostatin-1 interacts with the apoptosis signaling pathway during this process. This pathway could be a new neuroprotective and therapeutic target in Parkinson's disease.
Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, Jiangsu Province, China.
Jing-Ru
JR
Wu
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical College, Xuzhou, Jiangsu Province, China.
Jie
J
Wang
Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu Province, China.
Sheng-Kui
SK
Zhou
Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu Province, China.
Long
L
Yang
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical College, Xuzhou, Jiangsu Province, China.
Jia-le
JL
Yin
Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, Jiangsu Province, China.
Jun-Ping
JP
Cao
Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu Province, China.
Yan-Bo
YB
Cheng
6-hydroxydopamine; PC12 cells; Parkinson's disease; apoptosis; autophagy; cytotoxicity; necroptosis; necrosis; necrostatin-1; nerve regeneration; neural regeneration; neurodegeneration; neurodegenerative disease; neuroprotection; programmed cell death