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5-Hydroxytryptophan inhibits β-casein biosynthesis and promotes goat mammary epithelial cell apoptosis through the JAK2/STAT5a axis and the HTR7

文献类型： 外文期刊

作者： Du, Wei 1 ; Zhang, Zhi Fei 1 ; Xiao, Jia Ying 1 ; Wang, Ying 1 ; Liu, Weng Yi 1 ; Zheng, Hui Ling 1 ;

作者机构： 1.Northwest A&F Univ, Coll Anim Sci & Technol, Shaanxi Key Lab Mol Biol Agr, Yangling, Shaanxi, Peoples R China

2.Guangdong Acad Agr Sci, Inst Anim Sci, Guangzhou, Peoples R China

关键词： 5-HTP; beta-casein; JAK2/STAT5a; apoptosis; mammary epithelial cell

期刊名称：JOURNAL OF ANIMAL SCIENCE （ 影响因子：3.3； 五年影响因子：3.1 ）

ISSN： 0021-8812

年卷期： 2023 年 101 卷

页码：

收录情况： SCI

摘要： 5-Hydroxytryptamine (5-HT) is an amine produced in both the mammary gland and the central nervous system. Tryptophan hydroxylase 1 (TPH1) catalyzes the conversion of 5-hydroxytryptophan (5-HTP) into l-tryptophan, which is then converted into 5-HT by monoamine-oxidase (MAO-A). In the mammary gland, 5-HT has been shown to have a variety of paracrine-autocrine actions, including suppressing lactation, controlling the destiny of mammary epithelial cells, and maintaining calcium homeostasis throughout the transition from pregnancy to lactation. To examine the effects of 5-HT on the composition of colostrum and milk, a total of 30 transition Guan Zhong dairy goats were intramuscularly injected with 5-HTP (1.0 mg/kg) every morning before feeding from 10 d before the projected parturition date to the day of parturition. The average number of days animals received injections was 8.2 +/- 3.2 d. 5-HTP treatment increased serum 5-HT concentration from days 5 to 2 relative to parturition (P < 0.05), and decreased the casein concentration of colostrum (P < 0.05). In the in vitro experiment, mammary epithelial cells isolated from three individual goats' mammary glands were separately treated with 200 mu M 5-HTP, 30 mu M PCPA (the specific inhibitor of TPH1), or 200 mu M 5-HTP + 50 mu M SB269970 (the selective antagonist of 5-HTR7). The results showed that 200 mu M 5-HTP inhibited the expression of beta-casein, downregulated the activity of the JAK2/ STAT5a signaling pathway, and promoted the apoptosis of goat mammary epithelial cells (GMECs) (P < 0.05). When GMECs were treated with 30 mu M Four-chloro-dl-phenylalanine (PCPA), a specific inhibitor of 5-HT synthesis, the mRNA expression of STAT5a and the phosphorylated STAT5a protein level were upregulated. The 50 mu M SB269970 treatment rescued the effects of 5-HTP on GMECs (P < 0.05). Taken together, the results indicated that 5-HTP exerted an inhibitory effect on beta-casein synthesis and a proapoptotic effect in GMECs via HTR7 and the JAK2/STAT5a axis.

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