The involvement of Eag1 potassium channels and miR-34a in rotenone-induced death of dopaminergic SH-SY5Y cells.

摘要: The loss of dopaminergic neurons and the resultant motor impairment are hallmarks Parkinson's disease. SH‑SY5Y cell line is a model neurons, allows for study neuronal injury. Previous studies have revealed changes in Ether go‑go 1 (Eag1) potassium channel expression during p53-induced apoptosis, regulatory involvement microRNA‑34a (miR‑34a) was demonstrated. In present study, Eag1 miR‑34a rotenone‑induced injury investigated. Rotenone neurotoxin, which often used to generate models disease, since it causes death nigrostriatal by inducing intracellular aggregation alpha synuclein ubiquitin. rotenone resulted dose‑dependent decrease viability, as 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide (MTT) trypan blue counting assays. addition, demonstrated be constitutively expressed cells, involved viability. Suppression with astemizole MTT assay. Astemizole also enhanced severity cells. RNA interference against Eag1, using synthetic small interfering RNAs (siRNAs), corroborated this finding, siRNAs potentiated Eag1‑targeted (kv10.1‑3 or EAG1hum_287) statistically significant 16.4‑23.5% increase vulnerability rotenone. An increased number apoptotic nuclei were observed cells transfected EAG1hum_287. Notably, siRNA intensified an caspase 3/7 activity. Conversely, inhibitor exert neuroprotective effects. viability exposed 24 48 h treated restored 8.4‑8.8%. conclusion, channels response rotenone-induced effect mir‑34a inhibitors merits further investigations animal