Wang Shuai, Pang Xuan, Cai Yujuan, Tian Xue, Bai Jingyi, Xi Mingchuan, Cao Jiaxue, Jin Long, Wang Xun, Wang Tao, Li Diyan, Li Mingzhou, Fan Xiaolan
State Key Laboratory of Swine and Poultry Breeding Industry, Sichuan Agricultural University, Chengdu, China.
State Key Laboratory of Swine and Poultry Breeding Industry, Sichuan Agricultural University, Chengdu, 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, China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan, China.
J Biol Chem. 2025 Feb;301(2):108121. doi: 10.1016/j.jbc.2024.108121. Epub 2024 Dec 21.
In recent years, the prevalence of extremely high-temperature climates has led to an increase in cases of acute heat stress (HS), 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 HS and kidney injury caused by endogenous fructose remains unclear. The study found that acute HS triggers the production of reactive oxygen species, 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 HS 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 HS-induced kidney injury.
近年来，极端高温气候的普遍存在导致急性热应激（HS）病例增加，急性热应激已被确定为导致各种肾脏疾病的一个因素。多元醇途径的终产物果糖与肾结石、慢性肾病和急性肾损伤等肾脏疾病有关。然而，急性热应激与内源性果糖引起的肾损伤之间的关系仍不清楚。该研究发现，急性热应激会触发活性氧的产生，进而激活Nrf-2和Akr1b3，导致肾细胞内源性果糖水平升高。进一步证明，内源性果糖水平升高在导致肾细胞损伤中起关键作用。此外，抑制Nrf-2可通过降低内源性果糖水平有效减轻急性热应激诱导的肾损伤。这些发现强调了急性应激导致的过量果糖对肾功能的有害影响，为未来急性热应激诱导的肾损伤的预防和治疗研究提供了新的视角。
