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

Area of Science:

• Neuroscience
• Molecular Biology
• Cell Biology

Background:

• Parkinson's disease (PD) pathogenesis involves complex molecular mechanisms.
• Growth differentiation factor 15 (GDF15) is implicated in PD, but its precise role and molecular pathways remain unclear.
• The HT22 neuronal cell line serves as a valuable model for investigating PD.

Purpose of the Study:

• To investigate the effects of GDF15 overexpression on mitochondrial function in an in vitro model of PD.
• To identify molecular pathways and gene expression changes associated with GDF15 in neuronal cells under stress.
• To elucidate the potential therapeutic mechanisms of GDF15 in PD.

Main Methods:

• HT22 cells were engineered to overexpress GDF15.
• Cells were treated with oligomycin to induce mitochondrial stress.
• Cell viability, oxygen consumption, and mitochondrial membrane potential were assessed.
• High-throughput RNA sequencing (RNA-seq) was employed to profile lncRNA and mRNA expression.
• Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed.
• Quantitative real-time PCR (qRT-PCR) was used for validation of selected differentially expressed lncRNAs (DElncRNAs).

Main Results:

• GDF15 overexpression significantly ameliorated oligomycin-induced decreases in cell viability, oxygen consumption, and mitochondrial membrane potential.
• RNA-seq identified numerous differentially expressed mRNAs (DEmRNAs) and DElncRNAs between GDF15-overexpressing and control groups.
• GO analysis highlighted the positive regulation of cell proliferation as a key enriched term, with Cav1 identified in this pathway.
• KEGG analysis revealed the PI3K-Akt signaling pathway as significantly enriched in the GDF15 intervention group.
• qRT-PCR results corroborated the RNA-seq findings.

Conclusions:

• GDF15 plays a protective role against mitochondrial dysfunction in neuronal cells.
• GDF15 may enhance mitochondrial function and promote cell proliferation in HT22 cells.
• The PI3K/Akt signaling pathway is likely involved in mediating the effects of GDF15.
• These findings provide insights into the molecular mechanisms of GDF15 in Parkinson's disease and suggest potential therapeutic targets.