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牛磺酸的体内平衡需要在斑马鱼胚胎早期发育过程中通过半胱氨酸亚磺酸脱羧酶进行从头合成。

Taurine homeostasis requires de novo synthesis via cysteine sulfinic acid decarboxylase during zebrafish early embryogenesis.

机构信息

Department of Animal Science and Technology, National Taiwan University, Taipei 106, Taiwan.

出版信息

Amino Acids. 2013 Feb;44(2):615-29. doi: 10.1007/s00726-012-1386-8. Epub 2012 Aug 21.

DOI:10.1007/s00726-012-1386-8
PMID:22907836
Abstract

Cysteine sulfinic acid decarboxylase (Csad) is the rate-limiting enzyme in the de novo biosynthesis of taurine. There are a number of physiological roles of taurine, such as bile salt synthesis, osmoregulation, lipid metabolism, and oxidative stress inhibition. To investigate the role of de novo synthesis of taurine during embryonic development, zebrafish csad was cloned and functionally analyzed. Semi-quantitative RT-PCR showed that csad transcripts are maternally deposited, while whole-mount in situ hybridization demonstrated that csad is expressed in yolk syncytial layer and various embryonic tissues such as notochord, brain, retina, pronephric duct, liver, and pancreas. Knockdown of csad significantly reduced the embryonic taurine level, and the affected embryos had increased early mortality and cardiac anomalies. mRNA coinjection and taurine supplementation rescued the cardiac phenotypes suggesting that taurine originating from the de novo synthesis pathway plays a role in cardiac development. Our findings indicated that the de novo synthesis pathway via Csad plays a critical role in taurine homeostasis and cardiac development in zebrafish early embryos.

摘要

半胱亚磺酸脱羧酶(Csad)是牛磺酸从头生物合成中的限速酶。牛磺酸具有多种生理作用,如胆汁盐合成、渗透压调节、脂质代谢和氧化应激抑制。为了研究牛磺酸从头合成在胚胎发育过程中的作用,克隆了斑马鱼 csad 并进行了功能分析。半定量 RT-PCR 显示 csad 转录物是母源沉积的,而整体原位杂交显示 csad 在卵黄合胞层和各种胚胎组织中表达,如脊索、脑、视网膜、前肾管、肝和胰腺。csad 的敲低显著降低了胚胎牛磺酸水平,受影响的胚胎早期死亡率增加且出现心脏异常。mRNA 共注射和牛磺酸补充挽救了心脏表型,表明来自从头合成途径的牛磺酸在心脏发育中起作用。我们的研究结果表明,通过 Csad 的从头合成途径在斑马鱼早期胚胎中对牛磺酸的动态平衡和心脏发育起着关键作用。

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