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

• Published in: Molecules (Basel, Switzerland) Vol. 27; no. 2; p. 484
• Main Authors: Erber, Luke, Liu, Shirelle, Gong, Yao, Tran, Phu, Chen, Yue
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 13.01.2022; MDPI
• Subjects: Amino acids; Angiogenesis; Animals; Biosynthesis; Cell culture; Cell cycle; Cell Line; Comparative analysis; Correlation analysis; Enzymes; Epigenetics; Fatty acids; Gene expression; Gene Expression Profiling; Gene Expression Regulation; Hippocampus; Hippocampus - metabolism; Homeostasis; Hypoxia; Hypoxia - metabolism; Iron; Iron - metabolism; Iron Deficiencies - genetics; Iron Deficiencies - metabolism; iron deficiency; Ischemia; MEF2 Transcription Factors - metabolism; Metabolism; Mice; Mitochondria; Myocyte enhancer factor 2; Neurological diseases; neuronal cells; Neurons - metabolism; Nutrient deficiency; oxygen sensing; Peptides; Phosphorylation; Physiology; Protein synthesis; Proteins; Proteome - analysis; Proteome - metabolism; Proteomes; Proteomics; Quantitative analysis; quantitative proteomics; Rats; Signal Transduction; Transcription factors; Transcription Factors - metabolism; Transcriptome; transcriptome analysis; Transcriptomes; Transcriptomics; hypoxia; hippocampus; neuronal cells; oxygen sensing; iron deficiency; transcriptome analysis; quantitative proteomics
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules27020484

Iron and oxygen deficiencies are common features in pathophysiological conditions, such as ischemia, neurological diseases, and cancer. Cellular adaptive responses to such deficiencies include repression of mitochondrial respiration, promotion of angiogenesis, and cell cycle control. We applied a systematic proteomics analysis to determine the global proteomic changes caused by acute hypoxia and chronic and acute iron deficiency (ID) in hippocampal neuronal cells. Our analysis identified over 8600 proteins, revealing similar and differential effects of each treatment on activation and inhibition of pathways regulating neuronal development. In addition, comparative analysis of ID-induced proteomics changes in cultured cells and transcriptomic changes in the rat hippocampus identified common altered pathways, indicating specific neuronal effects. Transcription factor enrichment and correlation analysis identified key transcription factors that were activated in both cultured cells and tissue by iron deficiency, including those implicated in iron regulation, such as HIF1, NFY, and NRF1. We further identified MEF2 as a novel transcription factor whose activity was induced by ID in both HT22 proteome and rat hippocampal transcriptome, thus linking iron deficiency to MEF2-dependent cellular signaling pathways in neuronal development. Taken together, our study results identified diverse signaling networks that were differentially regulated by hypoxia and ID in neuronal cells.