UFBP1 Ameliorates Heat Stress-Induced Apoptosis via Mitochondria-Mediated Pathway in Bovine Mammary Epithelial Cells
by
,
Yuan Li
1,2, 
Ran Yu
1,2,
Shujing Tan
1,2,
Yunlong Jiang
1,2,
Longwei Sun
1,2,
Manman Shen
1,2
,
Chuanjian Zhang
3,
Kunlin Chen
4 and
Chengmin Li
1,2,*
1
Jiangsu Key Laboratory of Sericultural and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, China
2
Key Laboratory of Silkworm and Mulberry Genetic Improvement, Ministry of Agriculture and Rural Affairs, The Sericultural Research Institute, Chinese Academy of Agricultural Sciences, Zhenjiang 212100, China
3
Institute of Veterinary Immunology and Engineering, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China
4
Institute of Animal Science, Jiangsu Academy of Agricultural Sciences, Ministry of Agriculture and Rural Affairs, Nanjing 210014, China
*
Author to whom correspondence should be addressed.
Animals 2025, 15(9), 1233; https://doi.org/10.3390/ani15091233
Submission received: 24 February 2025
/
Revised: 2 April 2025
/
Accepted: 24 April 2025
/
Published: 27 April 2025
(This article belongs to the Special Issue Genetic Research for Improving Livestock Heat Stress Resistance)
Simple Summary
Global warming exacerbates heat stress in dairy cows, leading to apoptosis and decreased secretion function in bovine mammary epithelial cells (BMECs). UFBP1 (Ufm1-binding protein 1) functions as a critical element in ufmylation, which is crucial for the maintenance of cellular homeostasis. In the present study, we explored the role of UFBP1 in heat stress-induced apoptosis in mammary epithelial cells. The results showed that UFBP1 significantly alleviated the increase in reactive oxygen species (ROS), mitochondrial impairment and cell apoptosis triggered by thermal stress in BMECs. Moreover, overexpression of UFBP1 restored the expression of genes involved in the biosynthesis of milk fat and protein. These results indicated that UFBP1 possessed potential therapeutic value for mitigating heat stress in dairy cows.
Abstract
Heat stress in dairy cows is aggravated by Global warming, which negatively affects their performance and health, especially high yielding cows are more susceptible to high temperature and humidity in summer. Besides increasing body temperature and reducing feed intake, heat stress also compromises mammary gland function by inducing apoptosis in bovine mammary epithelial cells (BMECs). UFBP1 (Ufm1-binding protein 1) serves as an essential component of ufmylation, is crucial for the preservation of cellular homeostasis. However, little is known about its contribution to heat stress-induced apoptosis in BMECs. Therefore, the present study aimed to elucidate the effect of UFBP1 on heat stress-induced apoptosis through knockdown and overexpression of UFBP1 in BMECs. The results showed that heat stress triggered cell apoptosis (increased apoptosis rate and Bax/Bcl-2 protein expression) and decreased the expression of genes associated with the production of milk fat and protein both in vivo and in vitro studies. Furthermore, UFBP1 silencing aggravated the high-temperature-induced cell damage, and overexpression of UFBP1 attenuated heat stress-induced mitochondrial dysfunction, as evidenced by increased mitochondrial membrane potential (MMP), ATP synthesis and NAD+/NADH ratio, as well as the reduced reactive oxygen species (ROS) generation. Importantly, the mitochondrial apoptosis pathway triggered by heat stress was blocked by UFBP1, as indicated by the reduced apoptosis rate and Bax/Bcl-2 protein expression. In addition, UFBP1 restored the expression of milk fat and protein-related genes in heat-stressed BMECs. In conclusion, these findings indicate that UFBP1 may serve as a promising therapeutic target for ameliorating heat stress in dairy cows, thereby providing novel theoretical insights into the mitigation of adverse thermal stress effects on livestock productivity.
