Comparative proteomic study of early hypoxic response in the cerebral cortex of rats submitted to two different hypoxic models

Abstract

Purpose: The present study analyses and compares the cortical brain proteomic profiles of two different models of cerebral hypoxic insult in rats (HH: hypobaric hypoxia and HHI: ischemia followed by hypobaric hypoxia) in an attempt to describe the alterations of the early molecular hypoxic adaptive response underlying each one.

Experimental design: A quantitative proteomic profile of left-brain cortices of rats under HH, HHI, and control conditions was determined using isobaric labeling (Tandem Mass Tag™) on the protein extracts from pools of five individuals. Data are available via ProteomeXchange with identifier PXD004091.

Results: Altogether, 339 proteins were confidently quantified, 99 of them showing significant variations in the hypoxic conditions with respect to the control. The HHI model presents a global effect of protein downregulation while HH produces an overall increase of the protein levels. While HH mainly affecting oxidative and energetic metabolism, HHI also interferes with synaptic transmission, neurotransmitter secretion, substantia nigra development, and triggers apoptosis through mitochondrial pathway.

Conclusions and clinical relevance: The findings obtained show an overview of protein alterations under two hypoxic models of different aetiology and provide a basis for more detailed studies in order to unravel new specific mechanisms and therapies for hypoxic pathologies.

Keywords: Hypoxia; Ischemia; Proteomics; TMT.