Tseng H C, Graves D J
Neuroscience Program and Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, Iowa, 50011, USA.
Biochem Biophys Res Commun. 1998 Sep 29;250(3):726-30. doi: 10.1006/bbrc.1998.9382.
The natural osmolyte trimethylamine N-oxide (TMAO) at 200 mM increases the extent and the rate of formation of polymerized microtubule (MT) complex caused by tau. TMAO at this concentration has no effect on tubulin alone. Urea at 200 mM blocks tubulin assembly caused by tau, but this inhibition can be reversed by an equal amount of TMAO. Besides TMAO, betaine, another natural osmolyte, was found to have the same effects on MT as TMAO. On the contrary, glycerol (a carbohydrate osmolyte) and glycine (an amino acid osmolyte) do not increase tau-induced MT assembly. The mechanism by which TMAO and betaine enhance tau's effectiveness is not known, but physical studies suggest that the secondary structure of tau is not appreciably changed by 200 mM TMAO. This is the first report showing that natural osmolytes, TMAO and betaine, at a near physiological concentration are able to stimulate tau-induced tubulin assembly.
200 mM的天然渗透剂氧化三甲胺（TMAO）可增加由tau蛋白引起的聚合微管（MT）复合物形成的程度和速率。该浓度的TMAO对单独的微管蛋白没有影响。200 mM的尿素可阻断由tau蛋白引起的微管蛋白组装，但等量的TMAO可逆转这种抑制作用。除了TMAO，另一种天然渗透剂甜菜碱对MT的作用与TMAO相同。相反，甘油（一种碳水化合物渗透剂）和甘氨酸（一种氨基酸渗透剂）不会增加tau蛋白诱导的MT组装。TMAO和甜菜碱增强tau蛋白有效性的机制尚不清楚，但物理研究表明，200 mM的TMAO不会明显改变tau蛋白的二级结构。这是第一份表明接近生理浓度的天然渗透剂TMAO和甜菜碱能够刺激tau蛋白诱导的微管蛋白组装的报告。
