Acute heat stress upregulates Akr1b3 through Nrf-2 to increase endogenous fructose leading to kidney injury

Shuai Wang; Xuan Pang; Yujuan Cai; Xue Tian; Jingyi Bai; Mingchuan Xi; Jiaxue Cao; Long Jin; Xun Wang; Tao Wang; Diyan Li; Mingzhou Li; Xiaolan Fan

doi:10.1016/j.jbc.2024.108121

Acute heat stress upregulates Akr1b3 through Nrf-2 to increase endogenous fructose leading to kidney injury

J Biol Chem. 2024 Dec 20:108121. doi: 10.1016/j.jbc.2024.108121. Online ahead of print.

Authors

Shuai Wang¹, Xuan Pang¹, Yujuan Cai¹, Xue Tian¹, Jingyi Bai¹, Mingchuan Xi¹, Jiaxue Cao², Long Jin², Xun Wang², Tao Wang³, Diyan Li³, Mingzhou Li⁴, Xiaolan Fan⁵

Affiliations

¹ State Key Laboratory of Swine and Poultry Breeding Industry, Sichuan Agricultural University, Chengdu, 611130, China.
² State Key Laboratory of Swine and Poultry Breeding Industry, Sichuan Agricultural University, Chengdu, 611130, China; Livestock and Poultry Multi-omics Key Laboratory of Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, 611130, China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan, China.
³ Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, School of Pharmacy,Chengdu University, Chengdu, China.
⁴ State Key Laboratory of Swine and Poultry Breeding Industry, Sichuan Agricultural University, Chengdu, 611130, China; Livestock and Poultry Multi-omics Key Laboratory of Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, 611130, China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan, China. Electronic address: mingzhou.li@sicau.edu.cn.
⁵ State Key Laboratory of Swine and Poultry Breeding Industry, Sichuan Agricultural University, Chengdu, 611130, China; Livestock and Poultry Multi-omics Key Laboratory of Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, 611130, China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan, China. Electronic address: xiaolanfan@sicau.edu.sn.

PMID: 39710324
DOI: 10.1016/j.jbc.2024.108121

Abstract

In recent years, the prevalence of extremely high-temperature climates, has led to an increase in cases of acute heat stress, which has been identified as a contributing factor to various kidney diseases. Fructose, the end product of the polyol pathway, has been linked to kidney conditions such as kidney stones, chronic kidney disease and acute kidney injury. However, the relationship between acute heat stress and kidney injury caused by endogenous fructose remains unclear. The study found that acute heat stress triggers the production of reactive oxygen species (ROS), which in turn activate the Nrf-2 and Akr1b3 leading to an increase in endogenous fructose levels in kidney cells. It was further demonstrated that the elevated levels of endogenous fructose play a crucial role in causing damage to kidney cells. Moreover, inhibiting Nrf-2 effectively mitigated kidney damage induced by acute heat stress by reducing endogenous fructose levels. These findings underscore the detrimental impact of excessive fructose resulting from acute stress on kidney function, offering a novel perspective for future research on the prevention and treatment of acute heat stress-induced kidney injury.

Keywords: Akr1b3; Fructose; Heat stress; Kidney; Nrf-2.