The effect of acute hypoxic exercise on the protein kinase A/ arachidonic acid/ transient receptor potential vanilloid 4 pathway in the prefrontal cortex of rats

Wenlei Xu; Xing Huang; Xiaolong Wu

doi:10.1016/j.abb.2024.110214

The effect of acute hypoxic exercise on the protein kinase A/ arachidonic acid/ transient receptor potential vanilloid 4 pathway in the prefrontal cortex of rats

Arch Biochem Biophys. 2024 Nov 18:110214. doi: 10.1016/j.abb.2024.110214. Online ahead of print.

Authors

Wenlei Xu¹, Xing Huang², Xiaolong Wu¹

Affiliations

¹ Capital University of Physical Education and Sports, Beijing 100191, China.
² Capital University of Physical Education and Sports, Beijing 100191, China. Electronic address: huangxing@cupes.edu.cn.

PMID: 39566673
DOI: 10.1016/j.abb.2024.110214

Abstract

Acute hypoxic exercise will cause insufficient oxygen supply in brain tissue, and a succession of variations such as central dysfunction will occur. For example, the muscles don't have an adequate supply of oxygen, which leads to decrease in exercise capacity [1]. The prefrontal cortex in the brain is primarily responsible for regulating the executive functions of the brain. TRPV4 channel is a cation channel with permeability to Ca²⁺. Signals such as hypotonic solution stimulation, cell swelling, temperature stimulation, mechanical stimulation, arachidonic acid and its metabolites can activate TRPV4 channel.

Purpose: In conditions of ischemia and hypoxia, the central nervous system of the brain is damaged. Therefore, studying the biological mechanism of TRPV4 pathway can help prevent the damage caused by cerebral ischemia and hypoxia to the human.

Results: Studies have found that PKA-mediated phosphorylation at Ser-824 affects AA. This is an important signaling pathway for coronary dilatation. This signaling pathway can activate TRPV4 channels. Therefore, we studied the effect of acute hypoxic exercise on the PKA/AA/TRPV4 pathway in the prefrontal cortex of rats. Furthermore, we concluded that the hypoxic environment can shorten the time of increasing load exercise in rats. In this way, the rat entered a state of exhaustion in advance, and the exercise ability was significantly reduced. After further study, blocking TRPV4 channel can prolong the time of incremental load exercise in hypoxic environment, and the exercise ability is improved. Acute hypoxic exercise led to an increase in the concentration of 14,15-EET, which was speculated to be one of the reasons for the increased expression of TRPV4 channels. Acute hypoxic exercise can activate the PKA/AA/TRPV4 signaling pathway in the prefrontal cortex of rats. Further research on blocking the TRPV4 channel can alleviate the activation of the PKA/AA/TRPV4 signaling pathway in the prefrontal cortex of rats by acute hypoxic exercise.

Conclusion: These results suggest that blocking the TRPV4 channel may be one of the ways to reduce the damage and apoptosis of prefrontal cortex cells in rats due to acute hypoxic exercise. In future studies, multiple time points will be selected for collection. Alternatively, TRPV4 agonists, PKA agonists or blockers and 14,15-EET agonists or blockers can be added for further pathway validation. To provide a biological mechanism for the study of nutrient targets on the problem of reduced exercise capacity when military personnel and travel enthusiasts first went to the plateau. Better medical reference for athletes training at high altitudes or patients with respiratory issues.

Keywords: 14,15-EET; PKA; TRPV4; hypoxic exercise.