N-acetylcysteine (NAC) Attenuating Apoptosis and Autophagy in RAW264.7 Cells in Response to Incubation with Mycolic Acid from Bovine Mycobacterium tuberculosis Complex
N-acetylcysteine (NAC) Attenuating Apoptosis and Autophagy in RAW264.7 Cells in Response to Incubation with Mycolic Acid from Bovine Mycobacterium tuberculosis Complex
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N-乙酰半胱氨酸 (NAC) 减弱 RAW264.7 细胞中牛结核分枝杆菌复合体分枝酸孵育后的细胞凋亡和自噬
DOI：
10.33073/pjm-2020-026
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发表时间：
2020-01-01
影响因子：
2.1
通讯作者：
Wang, Yujiong
中科院分区：
文献类型：
--
作者：
Lin, Xue;Wei, Mengmeng;Wang, Yujiong
摘要牛结核病是由结核分枝杆菌复合群引起的一种空气传播的传染病。分枝菌酸（MA）是结核分枝杆菌细胞膜的主要脂质成分。它被NAD（P）H非酶促还原，并进一步产生活性氧（ROS），这可能导致人体细胞中的氧化应激。N-乙酰半胱氨酸（NAC）是谷胱甘肽（GSH）的合成前体，具有抗ROS活性。然而，其保护特性的潜在机制仍不确定。在此，在用NAC预孵育RAW264.7细胞后，测量与凋亡和自噬相关的因子。机制上，NAC可以减少MA诱导的促凋亡和促自噬蛋白的表达。在mRNA水平，NAC可抑制AMPK并激活mTOR表达。结果提示NAC可能通过AMPK/mTOR通路调控RAW264.7细胞的自噬。为了进一步证明NAC对MA的影响，使用ICR小鼠来评价肺损伤。对肺进行苏木精-伊红（HE）染色。结果表明，NAC可减轻MA引起的细胞损伤。总之，我们的研究表明，NAC减弱细胞凋亡和自噬反应与分枝菌酸孵育。
Abstract Bovine tuberculosis is an airborne infectious disease caused by organisms of the Mycobacterium tuberculosis (MTB) complex. Mycolic acid (MA) is the main lipid component of the cell membrane of MTB. It is non-enzymatically reduced by NAD(P)H and further produces reactive oxygen species (ROS), which can cause oxidative stress in human cells. N-acetylcysteine (NAC) is a synthetic precursor of glutathione (GSH) and exhibits anti-ROS activity. However, the underlying mechanisms of its protective properties remain uncertain. Herein, after pre-incubation of RAW264.7 cells with NAC, the factors associated with apoptosis and autophagy were measured. Mechanistically, NAC could reduce MA-induced expression of pro-apoptotic and pro-autophagy proteins. At the mRNA level, NAC can inhibit AMPK and activate mTOR expression. The results indicate that NAC might regulate autophagy in RAW264.7 cells through the AMPK/mTOR pathway. To further prove the effect of NAC on MA, ICR mice were used to evaluate the lung injury. Hematoxylin-eosin (HE) staining was performed on the lung. The results show that NAC could reduce cell injury induced by MA. In conclusion, our research showed that NAC attenuates apoptosis and autophagy in response to incubation with mycolic acid.