Saito M, Sugiyama K
Department of Clinical Pharmacology and Therapeutics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, 422-8526, Shizuoka, Japan.
Biochim Biophys Acta. 2000 Oct 18;1523(2-3):230-5. doi: 10.1016/s0304-4165(00)00127-6.
Adults rats with hypothyroidism were prepared by administration of 6-propyl-2-thiouracil (PTU) or methimazole, and the tissues were examined for their gangliosides through methods including glycolipid-overlay techniques. Normal thyroid tissue contained GM3, GD3, and GD1a as the major gangliosides, with GM1, GD1b, GT1b, and GQ1b in lesser amounts. The goitrous tissue of PTU-induced hypothyroid rats had higher concentrations of GM1 and GD1a with a concomitant decrease of GM3. The amount of GT3 in thyroid tissue was increased in hypothyroid animals. While normal liver tissue had a complex ganglioside pattern with a- and b-series gangliosides, the PTU-induced hypothyroid tissue showed a simpler ganglioside profile that consisted mainly of a-series gangliosides with almost undetectable amounts of b-series gangliosides. The expression of c-series gangliosides was suppressed in the hypothyroid liver tissue. Heart tissue had higher contents of GM3 and GT3 than control. No apparent change was observed in the compositions of major and c-series gangliosides in other extraneural tissues (i.e., kidney, lung, spleen, thymus, pancreas, testis, skeletal muscle, and eye lenses), and neural tissues (i.e., cerebrum and cerebellum) from PTU-induced hypothyroid rats. The ganglioside changes of thyroid, liver, and heart tissues were reproduced in corresponding tissues of methimazole-induced hypothyroid rats. These results suggest that hypothyroid conditions affect the biosynthesis and expression of gangliosides in specific tissue and cell types.
通过给予6-丙基-2-硫氧嘧啶（PTU）或甲巯咪唑制备成年甲状腺功能减退大鼠，并通过包括糖脂覆盖技术在内的方法检测组织中的神经节苷脂。正常甲状腺组织以GM3、GD3和GD1a作为主要神经节苷脂，GM1、GD1b、GT1b和GQ1b含量较少。PTU诱导的甲状腺功能减退大鼠的甲状腺肿组织中GM1和GD1a浓度较高，同时GM3减少。甲状腺功能减退动物的甲状腺组织中GT3含量增加。正常肝脏组织具有复杂的神经节苷脂模式，包含a系列和b系列神经节苷脂，而PTU诱导的甲状腺功能减退组织显示出更简单的神经节苷脂谱，主要由a系列神经节苷脂组成，几乎检测不到b系列神经节苷脂。甲状腺功能减退肝脏组织中c系列神经节苷脂的表达受到抑制。心脏组织中GM3和GT3的含量高于对照组。在PTU诱导的甲状腺功能减退大鼠的其他非神经组织（即肾脏、肺、脾脏、胸腺、胰腺、睾丸、骨骼肌和晶状体）以及神经组织（即大脑和小脑）中，主要和c系列神经节苷脂的组成没有明显变化。甲巯咪唑诱导的甲状腺功能减退大鼠的相应组织中再现了甲状腺、肝脏和心脏组织的神经节苷脂变化。这些结果表明，甲状腺功能减退状态会影响特定组织和细胞类型中神经节苷脂的生物合成和表达。
