FASEB：仿照河豚鱼肝肾病患者有望减少血液中氨毒死亡

生物谷

    全世界每年有许多肝病和肾病患者因血液中氨含量过多而中毒死亡，对此，美国和日本科学家表示，他们已寻找到可降低患者血液中氨含量的方法。  　　

    在4月份出版的《FASEB》杂志上，科学家介绍说，河豚鱼体内的一种蛋白能将氨从其腮中排出体外，这种蛋白同人体Rh血蛋白极其类似，因此通过对Rh血蛋白的研究，有望开发出帮助患者排出体内有害氨的新方法。

    对肝病和肾病患者而言，及时有效地排除体内自然产生的氨十分重要。人类因为大脑十分容易受到氨的影响，低含量氨能够导致患者出现轻微或严重的思绪混乱、睡意或颤栗，而高含量氨则导致他们昏迷并最终死亡。人体中的Rh血蛋白通常用于帮助人们决定血型，例如具有A、B、AB或O阳性血型的人，其体内红血细胞表面有Rh血蛋白，而具有A、B、AB或O阴性血型的人，其体内红血细胞表面则没有Rh血蛋白。

    科学家表示，Rh血蛋白将是今后医治肝病患者体内自然产生的高氨含量的方向。在研究报告中，科学家介绍了河豚利用类似人体Rh血蛋白的蛋白将氨排出其体外的微观过程。据悉，他们的发现与Rh血蛋白存在于许多有机物的事实结合起来，还有助于揭开进化论之谜。因为它表明，Rh血蛋白出现在动物系统进化的早期，并一直在排出体内氨方面起着十分重要的作用。

部分英文原文：

The FASEB Journal. 2007;21:1067-1074.

Ammonia secretion from fish gill depends on a set of Rh glycoproteins

Tsutomu Nakada*, Connie M. Westhoff {dagger} , {ddagger} , Akira Kato* and Shigehisa Hirose*,1

* Department of Biological Sciences, Tokyo Institute of Technology, Yokohama, Japan;

{dagger} Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA; and

{ddagger} American Red Cross, Philadelphia, Pennsylvania, USA

1Correspondence: Department of Biological Sciences, Tokyo Institute of Technology, 4259-B-19 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan. E-mail: shirose@bio.titech.ac.jp

Ammonia excretion from the gill in teleost fish is essential for nitrogen elimination. Although numerous physiological studies have measured ammonia excretion, the mechanism of ammonia movement through the membranes of gill epithelial cells is still unknown. Mammalian Rh glycoproteins are members of a family of proteins that mediate ammonia transport in bacteria, yeast, and plants. We identified the Rh glycoprotein homologs, fRhag, fRhbg, fRhcg1, and fRhcg2, of the pufferfish, Takifugu rubripes. Northern blot, in situ hybridization, and immunohistochemistry revealed that the pufferfish erythroid Rh glycoprotein homologue fRhag was present in red blood cells and the hematological organs (spleen and kidney) in fish. All four pufferfish Rh glycoproteins are specifically localized in the gill and line the pillar cells, pavement cells, and the mitochondrion-rich cells. Heterologous expression in Xenopus oocytes showed that they mediate methylammonium (an analog of ammonium) transport. These results suggest that pufferfish Rh glycoproteins are involved in ammonia excretion from the gill. These findings challenge the classic view that ammonia excretion in the fish gill occurs by passive diffusion.—Nakada, T., Westhoff, C. M., Kato, A., Hirose, S. Ammonia secretion from fish gill depends on a set of Rh glycoproteins.

Key Words: RhAG • Rhesus glycoprotein • ammonium transporter • mitochondria-rich cell • teleost

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