Hypoxia Induced Sex-Difference in Zebrafish Brain Proteome Profile Reveals the Crucial Role of H3K9me3 in Recovery From Acute Hypoxia

• DOI: 10.3389/fgene.2021.635904
• Publication Date: 2022-01-31T07:12:56Z
• Authors: Tapatee Das; Avijeet Kamle; Arvind Kumar; Sumana Chakravarty
• Keywords: Hypoxia; Proteome; KLF4

Understanding the molecular basis of sex differences in neural response to acute hypoxic insult has profound implications for effective prevention and treatment ischemic stroke. Global hypoxic-ischemic induced damage been studied recently under well-controlled, non-invasive, reproducible conditions using a zebrafish model. Our earlier report on difference global hypoxia-induced recovery prompted us conduct comprehensive study mechanisms underlying recovery. An omics approach studying quantitative changes brain proteome upon hypoxia following was undertaken iTRAQ-based LC-MS/MS approach. The results shed light altered expression many regulatory proteins differentially expressed along with uniform direction both sexes studied. Core analysis by Ingenuity Pathway Analysis (IPA) showed distinct disease function heatmap. Most upstream regulators obtained through IPA were validated at transcriptional level. Translational upregulation H3K9me3 males led elucidate mechanism confirming targets ChIP-qPCR. level 4 h post-hypoxia appears affect early neurogenic markers nestin, klf4, sox2, which might explain late males, compared females. Acute sex-specific comparison reveal proteins, can be further development novel better therapeutic strategy.