GDF-15 promotes mitochondrial function and proliferation in neuronal HT22 cells.

The neuronal cell line HT22 is an excellent model for studying Parkinson's disease. Growth differentiation factor 15 (GDF15) plays a critical role in Parkinson's disease, but the molecular mechanism involved are not well understood. We constructed the GDF15 overexpression HT22 cells and detected the effects of overexpression of GDF15 on the viability, oxygen consumption, mitochondrial membrane potential of oligomycin-treated HT22 cells. In addition, we used a high-throughput RNA-sequencing to study the lncRNA and mRNA expression profiling and obtained key lncRNAs, mRNA, gene ontology (GO), and Kyoto encyclopedia of genes and genomes (KEGG) pathway. The expression of selected DElncRNAs was validated by quantitative real-time PCR (qRT-PCR). Our results showed that overexpression of GDF15 significantly reversed the cells viability, oxygen consumption, and mitochondrial membrane potential effect caused by oligomycin in HT22 cells. The 1093 DEmRNAs and 395 DElncRNAs in HT22 cells between GDF15-oligomycin non-intervention group and a normal control-oligomycin un-intervention group were obtained, and 394 DEmRNAs and 271 DElncRNAs in HT22 cells between GDF15-oligomycin intervention group and normal control-oligomycin intervention group were identified. Base on the GO and KEGG enrichment analysis of between GDF15-oligomycin intervention group and normal control-oligomycin intervention group, positive regulation of cell proliferation was most significantly enriched GO terms, and Cav1 was enriched in positive regulation of cell proliferation pathway. PI3K-Akt signaling pathway was one significantly enriched pathway in GDF15-oligomycin intervention group. The qRT-PCR results were consistent with RNA-sequencing, generally. GDF15 might promote mitochondrial function and proliferation of HT22 cells by regulating PI3K/Akt signaling pathway. Our study may be helpful in understanding the potential molecular mechanism of GDF15 in Parkinson's disease.