Butyrate alleviates oxidative stress by regulating NRF2 nuclear accumulation and H3K9/14 acetylation via GPR109A in bovine mammary epithelial cells and mammary glands
Butyrate alleviates oxidative stress by regulating NRF2 nuclear accumulation and H3K9/14 acetylation via GPR109A in bovine mammary epithelial cells and mammary glands
复制标题
丁酸盐通过 GPR109A 调节 NRF2 核积累和 H3K9/14 乙酰化来减轻牛乳腺上皮细胞和乳腺中的氧化应激
DOI：
10.1016/j.freeradbiomed.2020.01.016
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发表时间：
2020-05-20
影响因子：
7.4
通讯作者：
Fu, Shoupeng
中科院分区：
文献类型：
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作者：
Guo, Wenjin;Liu, Juxiong;Fu, Shoupeng
氧化应激持续影响奶牛的哺乳期长度和质量。高产奶牛乳腺中的氧化应激是一个严重的问题。因此，我们研究了丁酸在奶牛氧化应激中的作用，并进一步阐明了乳牛乳腺上皮细胞抗氧化作用的机制。高产奶牛体内存在氧化应激和Gpr109a活性。分离牛乳腺上皮细胞，检测氧化应激相关蛋白的表达，证实丁酸钠通过Gpr109a、NRF2和H3K9/14乙酰化发挥抗氧化作用。为了进一步研究丁酸在奶牛体内的抗氧化机制，我们还通过Western blotting证实了丁酸通过AMPK信号通路促进NRF2核积聚和H3K9/14乙酰化。此外，我们还利用Co-IP和CHIP初步阐明了NRF2与H3K9/14 ACET甲基化的相互作用。丁酸通过Gpr109a激活AMPK信号通路，促进NRF2核聚集和H3K9/14乙酰化，进而通过这两个过程的协同作用发挥抗氧化作用。然后，我们在体内研究了丁酸对奶牛氧化应激的影响，结果与体外的结果一致。因此，丁酸盐通过Gpr109a/AMPK/NRF2信号通路发挥抗氧化和抗凋亡作用，而H3K9/14乙酰化可促进NRF2转录，增强BMECs的抗氧化能力。
Oxidative stress consistently affects lactation length and quality in dairy cows. Oxidative stress in the mammary gland of high -yielding dairy cows is a serious problem. Therefore, we studied the role of butyrate in dairy cow oxidative stress and further elucidated the mechanism of the antioxidative action of mammary epithelial cells in dairy cows. Oxidative stress and activated GPR109A were present in high -yielding dairy cows. Then, bovine mammary epithelial cells (BMECs) were isolated, and oxidative stress -related protein expression was measured, confirming that sodium butyrate (NaB) exerted antioxidant effects through GPR109A, NRF2 and H3K9/14 acetylation. To further study the antioxidative mechanism of butyrate in dairy cows, we also confirmed that butyrate promoted NRF2 nuclear accumulation and H3K9/14 acetylation through the AMPK signaling pathway by western blotting. Additionally, we preliminarily clarified the interaction between NRF2 and H3K9/14 acet- ylation by Co-IP and ChIP. Butyrate activated the AMPK signaling pathway through GPR109A to promote NRF2 nuclear accumulation and H3K9/14 acetylation, subsequently exerting antioxidant effects through the sy- nergistic functions of these two processes. Then, we studied the effect of butyrate on oxidative stress in dairy cows in vivo , and the results were consistent with those in vitro . Therefore, butyrate played an antioxidant and antiapoptotic role through the GPR109A/AMPK/NRF2 signaling pathway, while H3K9/14 acetylation could promote NRF2 transcription and enhance the antioxidant capacity of BMECs.