Regulating glycolysis and heat shock proteins in Gannan yaks (Bos grunniens) in response to hypoxia of the Qinghai-Tibet Plateau.

Glycolysis and heat shock proteins (HSPs) play an important role in hypoxia-intolerant species during hypoxia conditions. This study was conducted to evaluate the differences of glycolysis and heat shock proteins (HSPs) in Gannan yaks (Bos grunniens), with the main goal of understanding how the response to hypoxia changes with altitude. Here, the genes and enzymes of glycolysis and HSPs were detected in heart, liver, lung, kidney, and longissimus dorsi from Gannan yaks at different altitude (2500 and 3500  $m$ ) using qPCR, western blot, and enzyme kits. The results showed that the expression of HIF1A and PDK4 was increased with altitude ( $P<0.01$ ) in above tissues. Significantly increased lactate dehydrogenase (LDH), adenosine triphosphate (ATP), and nicotinamide adenine dinucleotide (NADH) levels and the ratio of NADH/NAD ${}^{+}$ were also observed in heart, lung, and longissimus dorsi tissues ( $P<0.05$ ), as well as a decreased citric acid (CA) level ( $P<0.05$ ). Furthermore, we observed significant global increases in the protein and mRNA expression levels of both the ATP-independent HSP27 and the ATP-dependent HSP60 during hypoxic conditions ( $P<0.01$ ). These findings revealed that hypoxia-reprogrammed glucose metabolism promotes energy supply via up-regulated glycolysis and weakness of the tricarboxylic acid (TCA) cycle. HSPs were activated and the prioritization of cytoprotective protein chaperone functions over energy conservation in yak under hypoxic conditions. These results are useful to better understand the unique adaptability of yak, allowing them to survive in hypoxia conditions.