Investigation Of Cardiac Gene And Protein Expressions Associated With High-Altitude Adaptation In Yak

Qinghai–Tibet Plateau(QTP)is the highest elevated unique region and called to be the roof of world with standard height of ?4000-5000 meters above sea level.High altitude species are case of strong external factors to survive due to harsh environments like hypoxia,hyper radiation,cold and deficiency of biological production,creating these kind of species more valued example for evolutionary comparative analyses.Many factors influenced hypoxic adaptation as it is a complex attribute.Yaks inhabiting high-altitude are well-adapted to the hypoxic environments.Though,the mechanisms involved in regulatory genes and protein expression at high-altitude were not completely comprehended.Mammals inhabiting QTP show strong cardiac functions,and genes exhibiting expressions associated with hypoxia adaptation by cumulative systemic circulation,and protecting cardiac cells and tissue constructions.Both transcriptome and proteome analysis were previously used for screening functional genes elaboration in muscle growth lipid deposition in yak and other domestic species.To revel the molecular mechanism of hypoxic adaptation in yak,here we have applied comparative myocardial transcriptome and proteome analysis between yak and cattle by RNA-sequencing and iTRAQ labelling.To understand the systematic gene expression variations in myocardial tissues which involved in the hypoxic adaptation in yak,we have found 20646 genes were identified as differentially expressed genes(DEGs)in yak as compare to cattle by RNA-sequencing results,the DEGs(GSTA2,AHCYL2,SOD1,Idh1,GATM,HK3 and BCAA),in yak were found to be associated with high-altitude adaptation through intracellular calcium release,stabilization of HIF-1? under hypoxia,induce NADPH(Nicotinamide adenine dinucleotide phosphate)processes by altering isocitrate to ?-ketoglutarate and energy metabolism.Furthermore,our findings revealed that many DEGs were associated with very important KEGG pathways that are suggested to be associated with regulation of key signaling pathways involved in high altitude adaptation by mediating acute responses in endothelium activated in reaction to VEGF(vascular endothelial growth factor),trigger the inflammatory,cytotoxic and hypersensitivity functions and stressresponsive protein involved in protection of heart from ischemia reperfusion injury.To understand the systematic protein expression variations in myocardial tissues that involved in the hypoxic adaptation in yak,we have performed iTRAQ analysis pooled with LCMS/MS.Bioinformatics analysis was performed towards finding association of these differentially expressed proteins(DEPs)with different functions and pathways.By using STRING database,protein to protein interaction was analyzed for 64 proteins.686 DEPs were identified in yak as compare to cattle,in which 480 DEPs were expressed high and 206 were down-regulated in yak.Upregulated expression of ASB4,STAT,HRG,RHO and TSP4 in yak may be associated with angiogenesis,cardiovascular development,response to pressure overload to heart and regulation of myocardial contraction in response to increased oxygen tension.The up-regulation of mitochondrial proteins,ACAD8,GPDH-M,PTPMT1,and ALDH2,may have contributed to oxidation within mitochondria,hypoxia-induced cell metabolism and protection of heart against cardiac ischemic injuries.Further,the upregulated expression of SAA1,PTX,HP and MBL2 involved in immune response potentially helpful in myocardial protection against ischemic injuries,extracellular matrix remodeling and free heme neutralization/clearance in oxygen-deficient environment.Therefore,the identification of these myocardial genes and proteins will be conducive to investigate the mechanisms involved in molecular hypoxic adaptations of yak at high-altitude condition and hypothetically furnished novel visualizations of high-altitude adaptation in human and other animals.However,additional investigations are needed to confirm the DEGs and DEPs which were associated with the regulation of hypoxia,identified in this experiment.