Overexpression of Kir2.3 in PC12 cells resists rotenone-induced neurotoxicity associated with PKC signaling pathway.
Parkinson's disease (PD) can be triggered by genetic or environmental factors. Although the precise etiopathogenesis of the disease remains unknown, recent studies focusing on the K(+) channel gene have uncovered the dysfunctions in various K(+) channels (e.g., Kir2, Kv, K(ATP), and SKCa) that are involved in the pathological mechanisms underlying PD. Here we show that Kir2.3 overexpression can protect against rotenone-induced apoptosis in cell models in the neurodegenerative process, suggesting Kir2.3's general neuroprotective function. The protection of Kir2.3 against neurodegeneration may be associated with the protein kinase C (PKC) pathway, as PKC is downregulated by Kir2.3 overexpression and the PKC activator can reduce the protective effect of Kir2.3. Our studies provide an entry point for understanding the novel roles of Kir2.3 in cell models of PD, and they offer clues for the common mechanisms underlying different neurodegenerative conditions.
Wang
Gang
G
Department of Neurology & Neuroscience Institute, Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China. wgneuron@hotmail.com
Zeng
Jie
J
Shen
Cheng-Yu
CY
Wang
Zhi-Quan
ZQ
Chen
Sheng-Di
SD
D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D004247:DNA / Q000235:genetics; D016716:PC12 Cells; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000096:biosynthesis* / Q000235:genetics; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D012402:Rotenone / Q000633:toxicity; D015398:Signal Transduction; D014162:Transfection
C490968:Kcnj4 protein, rat; D024661:Potassium Channels, Inwardly Rectifying; D012402:Rotenone; D004247:DNA; D011493:Protein Kinase C