The Significance Of KCNA5 Knockdown And Over-expression For PC12 Apoptotsis And Proliferation

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 and participated in signaling pathway in neurons.KCNA5(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 KCNA5.Therefore,the molecular mechanisms involved in KCNA5channel functions in neurons may act as therapeutic targets in PD.Methods:Knockdown KCNA5 PC12 cell model was established with pSINsi-hU6-KCNA5 treated by the RNAi method.MTT,Western Blot and Realtime PCR were used to detect the influence of KCNA5 on PC12 cells proliferation,and the effect of KCNA5 on PC12 cells apoptosis after MPP~+treatment in vitro.Results:1)Knockdown and over-expressed KCNA5 participated in PC12 cells proliferation.Transiently over-expressed KCNA5 could boost the survival rate of PC12 cells,while transiently silence KCNA5 inhibited PC12 cells proliferation.But Knockdown KCNA5PC12 cells model didn’t effect PC12 cells double time.2)The effect of KCNA5 on PC12cells proliferation was through PI3K/Akt signaling pathway.Over-expressed KCNA5 could induce the activation of Akt,and Bcl-2 expression in PC12 cells;Knockdown KCNA5 in PC12 inhibited the activation of Akt,Bcl-2 expression,and promoted MAPK phosphorylation.3)Over-expressed KCNA5 could significantly prevent PC12 cell from apoptosis induced by MPP~+via activating Akt pathway and increasing Bcl-2 expression;Knockdown of KCNA5wass more sensitive than its control counterpart when treated with MPP~+for 48h.Conclution:KCNA5 could hinder MPP~+neurotoxicity to PC12 cells by PI3K/Akt signaling pathway.