1. Unveiling the regulatory role of SIRT1 in the oxidative stress response of bovine mammary cells.
- Author
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Zhang, Yufei, Liu, Juxiong, Yuan, Shuai, Liu, Shu, Zhang, Meng, Hu, Huijie, Cao, Yu, Hu, Guiqiu, Fu, Shoupeng, and Guo, Wenjin
- Subjects
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SIRTUINS , *OXIDANT status , *DAIRY cattle , *REACTIVE oxygen species , *AMP-activated protein kinases - Abstract
The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. High-yield dairy cows typically undergo intense cellular metabolism, leading to oxidative stress in their mammary tissues. Our study found that compared with ordinary cows, these high-yield cows had significantly elevated levels of H 2 O 2 , lipoperoxidase, and total antioxidant capacity in their blood. This increased oxidative stress is associated with heightened expression of genes such as GCLC , GCLM , and SIRT1 and proteins such as SIRT1 in the mammary tissue of high-yield cows. We stimulated MAC-T cells with H 2 O 2 at a concentration equal to the average H 2 O 2 level in the serum of ethically high-yielding cows, as detected by an assay kit. Our observations revealed that short-term exposure (12 h) to H 2 O 2 upregulated the expression of the SIRT1 gene and SIRT1 protein. It also increased gene expression for SOD2 , CAT , GCLC , GCLM , PGC-1α , and NQO1 , elevated the phosphorylation of AMPK, and enhanced protein expression of PGC-1α, NQO1, Nrf2, and HO-1, as well as reduced the phosphorylation of NF-κB. Additionally, short-term H 2 O 2 stimulation resulted in increased total antioxidant capacity and levels of superoxide dismutase, glutathione, and catalase in the mammary epithelial cells of dairy cows. In contrast, prolonged exposure to H 2 O 2 (24 h) yielded opposite results, indicating reduced antioxidant capacity. Further investigation showed that the SIRT1 inhibitor EX 527 could reverse the enhanced cellular antioxidant capacity triggered by short-term oxidative stress. However, it is crucial to note that although 12 h of H 2 O 2 stimulation improved antioxidant capacity, reactive oxygen species (ROS) and malondialdehyde (MDA) levels inside the cell gradually increased over time, suggesting greater damage under long-term stimulation. Conversely, the SIRT1 activator SRT 2104 could reverse the reduced cellular antioxidant capacity caused by long-term oxidative stress and significantly inhibit the accumulation of ROS and MDA. Notably, SRT 2104 demonstrated similar effects in MAC-T cells during lactation. In summary, SIRT1 plays a crucial role in regulating the antioxidant capacity of mammary epithelial cells in dairy cows. This discovery provides valuable insights into the antioxidant mechanisms of mammary cells, which can serve as a theoretical foundation for future mammary health strategies. [Display omitted] [ABSTRACT FROM AUTHOR]
- Published
- 2024
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