Vig P J, Subramony S H, Currier R D, Desaiah D
Department of Neurology, University of Mississippi Medical Center, Jackson 39216.
J Neurol Sci. 1992 Jul;110(1-2):139-43. doi: 10.1016/0022-510x(92)90020-l.
We have investigated inositol 1,4,5-trisphosphate (InsP3) metabolism in cerebellar membranes of normal humans and patients with dominant ataxia ('C' kindred), and also in cerebellar microsomes of Lurcher mutant mouse (a suggested model for cerebellar ataxia). Various [3H]InsP3 metabolites formed were separated by HPLC using 3 successive convex gradients of 1.7 M ammonium formate, pH 3.7. [3H]InsP3 metabolism was rapid and in 15- and 45-day-old control mice cerebella about 50% of [3H]InsP3 was metabolized within 20 s. In 15-day-old Lurcher mice the rate of [3H]InsP3 metabolism was significantly low (40% of normal). [3H]InsP3 metabolism was almost absent in 45-day-old Lurcher mice cerebellar microsomes. The decreased [3H]InsP3 metabolism was consistent with decreased recovery of the various inositol polyphosphates formed. Similarly, in cerebellar membranes of human patients with olivopontocerebellar atrophy (OPCA) a significant decrease in [3H]InsP3 metabolism was observed when compared with normal controls. These data suggest that altered phosphoinositide turnover may be associated with the onset of neuronal degeneration in human OPCA.
我们研究了正常人和显性共济失调患者（“C”家族）小脑膜中的肌醇1,4,5-三磷酸（InsP3）代谢，还研究了Lurcher突变小鼠（一种提示的小脑共济失调模型）的小脑微粒体中的InsP3代谢。使用1.7 M甲酸铵（pH 3.7）的3个连续凸梯度，通过高效液相色谱法分离形成的各种[3H]InsP3代谢物。[3H]InsP3代谢迅速，在15日龄和45日龄对照小鼠的小脑中，约50%的[3H]InsP3在20秒内被代谢。在15日龄的Lurcher小鼠中，[3H]InsP3代谢率显著降低（为正常的40%）。在45日龄的Lurcher小鼠小脑微粒体中，[3H]InsP3代谢几乎不存在。[3H]InsP3代谢的降低与所形成的各种肌醇多磷酸的回收率降低一致。同样，与正常对照相比，在橄榄桥脑小脑萎缩（OPCA）患者的小脑膜中观察到[3H]InsP3代谢显著降低。这些数据表明，磷脂酰肌醇周转率的改变可能与人类OPCA中神经元变性的发生有关。
