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牛磺酸缺乏与细胞凋亡:来自牛磺酸转运体基因敲除小鼠的研究结果

Taurine deficiency and apoptosis: findings from the taurine transporter knockout mouse.

作者信息

Warskulat Ulrich, Borsch Elena, Reinehr Roland, Heller-Stilb Birgit, Roth Christian, Witt Martin, Häussinger Dieter

机构信息

Department of Gastroenterology, Hepatology and Infectiology, Heinrich-Heine-University Düsseldorf, Germany.

出版信息

Arch Biochem Biophys. 2007 Jun 15;462(2):202-9. doi: 10.1016/j.abb.2007.03.022. Epub 2007 Apr 9.

Abstract

Apoptosis is characterized by cell shrinkage, nuclear condensation, DNA-fragmentation and apoptotic body formation. Compatible organic osmolytes, e.g. taurine, modulate the cellular response to anisotonicity and may protect from apoptosis. Taurine transporter knockout mice (taut-/- mice) show strongly decreased taurine levels in a variety of tissues. They develop clinically important age-dependent diseases and some of them are characterized by apoptosis. Increased photoreceptor apoptosis leads to blindness of taut-/- mice at an early age. The taurine transporter may not be essential for the differentiation of photoreceptor cells, but many mature cells do not survive without an intact taurine transporter. The olfactory epithelium of taut-/- mice also exhibits structural and functional abnormalities. When compared with wild-types, taut-/- mice have a significantly higher proliferative activity of immature olfactory receptor neurons and an increased number of apoptotic cells. This is accompanied by electrophysiological findings indicating a reduced olfactory sensitivity. Furthermore, taut-/- and taut+/- mice develop moderate unspecific hepatitis and liver fibrosis beyond 1 year of age where hepatocyte apoptosis and activation of the CD95 system are pronounced.

摘要

细胞凋亡的特征是细胞皱缩、核固缩、DNA片段化以及凋亡小体形成。相容性有机渗透溶质,如牛磺酸,可调节细胞对非等渗状态的反应,并可能预防细胞凋亡。牛磺酸转运体基因敲除小鼠(taut-/-小鼠)多种组织中的牛磺酸水平显著降低。它们会患上具有临床重要性的年龄依赖性疾病,其中一些疾病的特征是细胞凋亡。光感受器细胞凋亡增加导致taut-/-小鼠在幼年时失明。牛磺酸转运体对于光感受器细胞的分化可能并非必不可少,但许多成熟细胞如果没有完整的牛磺酸转运体则无法存活。taut-/-小鼠的嗅觉上皮也表现出结构和功能异常。与野生型小鼠相比,taut-/-小鼠未成熟嗅觉受体神经元的增殖活性显著更高,凋亡细胞数量增加。这伴随着表明嗅觉敏感性降低的电生理结果。此外,taut-/-和taut+/-小鼠在1岁以后会发展为中度非特异性肝炎和肝纤维化,此时肝细胞凋亡和CD95系统的激活较为明显。

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