Quantitative Proteome and Transcriptome Dynamics Analysis Reveals Iron Deficiency Response Networks and Signature in...

Area of Science:

• Neuroscience
• Molecular Biology
• Cellular Biology

Background:

• Iron and oxygen deficiencies are prevalent in diseases like ischemia, neurological disorders, and cancer.
• Cells adapt to these deficiencies through mechanisms such as reduced mitochondrial respiration, enhanced angiogenesis, and cell cycle regulation.

Purpose of the Study:

• To investigate global proteomic changes in hippocampal neuronal cells due to acute hypoxia and iron deficiency (ID).
• To compare proteomic alterations in cultured cells with transcriptomic changes in rat hippocampus to identify specific neuronal effects of ID.

Main Methods:

• Systematic proteomics analysis of hippocampal neuronal cells under acute hypoxia and chronic/acute iron deficiency.
• Comparative analysis of proteomic data from cultured cells and transcriptomic data from rat hippocampus.
• Transcription factor enrichment and correlation analysis.

Main Results:

• Over 8600 proteins were identified, showing distinct and overlapping pathway regulations under hypoxia and ID.
• Comparative analysis highlighted common altered pathways in cultured cells and rat hippocampus, indicating specific neuronal responses to ID.
• Key transcription factors, including HIF1, NFY, NRF1, and notably MEF2, were identified as activated by ID in both models, linking ID to MEF2-dependent signaling in neuronal development.

Conclusions:

• Hypoxia and iron deficiency differentially regulate diverse signaling networks in neuronal cells.
• Iron deficiency activates specific transcription factors, including MEF2, impacting neuronal development pathways.
• The study provides insights into cellular adaptive responses to iron deficiency in the nervous system.