Cysteamine affects skeletal development and impairs motor behavior in zebrafish.
Cysteamine affects skeletal development and impairs motor behavior in zebrafish.
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半胱胺影响斑马鱼的骨骼发育并损害运动行为
DOI：
10.3389/fphar.2022.966710
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发表时间：
2022
影响因子：
5.6
通讯作者：
Cao, Zigang
中科院分区：
文献类型：
--
作者：
Chen, Chao;Zheng, Yongliang;Li, Xue;Zhang, Li;Liu, Kangyu;Sun, Sujie;Zhong, Zilin;Hu, Hongmei;Liu, Fasheng;Xiong, Guanghua;Liao, Xinjun;Lu, Huiqiang;Bi, Yanlong;Chen, Jianjun;Cao, Zigang
半胱胺是农业生产中常用的一种饲料添加剂。它也是治疗胱氨酸病的唯一靶向药物，在临床应用中存在一定的副作用。然而，潜在的骨骼毒性仍有待进一步阐明。本研究首次利用斑马鱼模型对半胱胺引起的骨骼发育缺陷进行综合评价。从受精后 6 小时 (hpf) 到 72 hpf，用 0.35、0.70 和 1.05 mM 半胱胺处理胚胎。显着的骨骼改变表现为体长缩短、软骨减少和体节发育异常。 24 hpf 时的自发尾部卷曲和 120 hpf 时的运动结果表明，半胱胺会降低行为能力。此外，暴露于半胱胺后，骨骼中的氧化应激水平升高。转录检查显示，半胱胺上调破骨细胞相关基因的表达，但不影响成骨细胞相关基因的表达。此外，半胱胺暴露导致Notch信号下调，Notch信号激活部分减轻了骨骼缺陷。总的来说，我们的研究表明半胱胺会导致骨骼发育缺陷并降低运动活动。这种危害可能与半胱胺介导的 Notch 信号传导抑制以及氧化应激和细胞凋亡导致的脊索细胞紊乱有关。
Cysteamine is a kind of feed additive commonly used in agricultural production. It is also the only targeted agent for the treatment of cystinosis, and there are some side effects in clinical applications. However, the potential skeletal toxicity remains to be further elucidated. In this study, a zebrafish model was for the first time utilized to synthetically appraise the skeletal developmental defects induced by cysteamine. The embryos were treated with 0.35, 0.70, and 1.05 mM cysteamine from 6 h post fertilization (hpf) to 72 hpf. Substantial skeletal alterations were manifested as shortened body length, chondropenia, and abnormal somite development. The results of spontaneous tail coiling at 24 hpf and locomotion at 120 hpf revealed that cysteamine decreased behavioral abilities. Moreover, the level of oxidative stress in the skeleton ascended after cysteamine exposure. Transcriptional examination showed that cysteamine upregulated the expression of osteoclast-related genes but did not affect osteoblast-related genes expression. Additionally, cysteamine exposure caused the downregulation of the Notch signaling and activating of Notch signaling partially attenuated skeletal defects. Collectively, our study suggests that cysteamine leads to skeletal developmental defects and reduces locomotion activity. This hazard may be associated with cysteamine-mediated inhibition of the Notch signaling and disorganization of notochordal cells due to oxidative stress and apoptosis.
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影响因子：
4.2
作者：
Chen, Shan;Lee, Brendan H.;Bae, Yangjin
通讯作者：
Bae, Yangjin
影响因子：
3.7
作者：
Hu R;Wang Z;Peng Q;Zou H;Wang H;Yu X;Jing X;Wang Y;Cao B;Bao S;Zhang W;Zhao S;Ji H;Kong X;Niu Q
通讯作者：
Niu Q
母体供应半胱胺可减轻猪胎盘的氧化应激并增强血管生成
影响因子：
7
作者：
Huang S;Wu Z;Huang Z;Hao X;Zhang L;Hu C;Wei J;Deng J;Tan C
通讯作者：
Tan C
影响因子：
8.9
作者：
Bai, Zhonghui;Jia, Kun;Lu, Huiqiang
通讯作者：
Lu, Huiqiang
影响因子：
2.1
作者：
Du, G.;Shi, Z.;Zhao, R.
通讯作者：
Zhao, R.