Voltage-Gated Potassium Channel KV1.5 Protects against MPP+ Mediated Neurotoxicity in PC12 Cells

Chao Qu
2014 Advances in Biochemistry  
Parkinson's disease (PD) is the second most common neurodegenerative disease and afflicts almost 1.8% of over 65-year-old group in the world. Epidemiological projections showed that the incidence of PD was increasing continuously each year, with a wider age range as well. A large number of studies indicated that voltage-gated potassium channel (Kv) played significant roles in cellular signaling in both excitable and non-excitable cells. What's more, Kv was also ubiquitously expressed in neurons
more » ... and participated in signaling pathway in neurons. Kv1.5 (encoded by KCNA5) is an important voltage-gated K + channel, which is not only necessary for critical processes such as cell proliferation and apoptosis but ubiquitously expressed in neurons. Recent studies reported that PD clinical drugs could inhibit the expression of Kv1.5. To determine the mechanisms by which Kv1.5 protects against MPP + mediated neurotoxicity in PC12 cells. Materials and Methods: Knockdown of Kv1.5 model was established with pSINsi-hU6-Kv1.5 treated by the RNAi method in PC12. MTT, and Western Blot were used to detect the influence of Kv1.5 on PC12 proliferation, and the effect of Kv1.5 on PC12 apoptosis after MPP + treatment in vitro. Results: 1) Knockdown and overexpression of Kv1.5 participated in PC12 proliferation. Transiently over-expressed Kv1.5 could boost the survival rate of PC12, while transiently knockdown of Kv1.5 inhibited PC12 proliferation. 2) The effect of Kv1.5 on PC12 proliferation was through PI3K/Akt signaling pathway. Over-expressed Kv1.5 could induce the activation of Akt, and Bcl-2 expression in PC12; Knockdown of Kv1.5 in PC12 inhibited the activation of Akt, Bcl-2 expression, and promoted MAPK phosphorylation. 3) Over-expressed Kv1.5 could significantly prevent PC12 from apoptosis induced by MPP + via activating Akt pathway and increasing Bcl-2 expression; Knockdown of Kv1.5 was more sensitive than its control counterpart when treated with MPP + for 24 h. Conclusion: Kv1.5 could hinder MPP + neurotoxicity to PC12 by PI3K/Akt signaling pathway.
doi:10.11648/j.ab.20140206.14 fatcat:424wjye6pzeptltti4sk4uhf6y