Yoshimura T, Kobayashi T, Mitsuo K, Goto I
Department of Neurology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
J Neurochem. 1989 Mar;52(3):836-41. doi: 10.1111/j.1471-4159.1989.tb02529.x.
We examined chronological changes of myelin proteins of the brainstem and spinal cord of the twitcher mouse (15, 20, and 30 days old), a murine model of human globoid cell leukodystrophy caused by a genetic deficiency of galactosylceramidase I activity. The yield of myelin was normal until postnatal day 20, whereas galactosylsphingosine (psychosine) accumulated with age in myelin. The protein profiles of myelin and the activity of 2',3'-cyclic nucleotide 3'-phosphodiesterase in the myelin remained normal throughout the experimental period. Fatty acylation of proteolipid protein (PLP) was examined in a cell-free system by incubation of myelin with [3H]palmitic acid, CoA, and ATP, and was normal at postnatal day 15, but decreased after postnatal day 20. Decreased fatty acylation of PLP was also observed in the twitcher mouse at postnatal day 20 when the isolated myelin was incubated with [14C]palmitoyl-CoA in the absence of ATP and CoA, or the slices of brainstem and spinal cord were incubated with [3H]palmitic acid. The activity of fatty acid:CoA ligase was reduced in myelin. These data suggest that decreased acylation of PLP in twitcher mouse myelin is probably due to reduced activities for both activation and transfer of fatty acid into PLP and that metabolic disturbance is present in myelin because acylation of PLP has been shown to occur in myelin membrane. Although psychosine (200 microM) inhibited only 17% of the acylation in vitro, it may be responsible for the reduced acylation of PLP in vivo.
我们研究了震颤小鼠（15日龄、20日龄和30日龄）脑干和脊髓髓鞘蛋白的时间变化，震颤小鼠是一种人类球状细胞脑白质营养不良的小鼠模型，由半乳糖神经酰胺酶I活性的基因缺陷引起。在出生后第20天之前，髓鞘的产量正常，而半乳糖神经鞘氨醇（精神活性物质）在髓鞘中随年龄积累。在整个实验期间，髓鞘的蛋白质谱和髓鞘中2',3'-环核苷酸3'-磷酸二酯酶的活性保持正常。通过将髓鞘与[3H]棕榈酸、辅酶A和ATP一起孵育，在无细胞系统中检测了蛋白脂蛋白（PLP）的脂肪酰化，在出生后第15天其正常，但在出生后第20天之后降低。当分离的髓鞘在没有ATP和辅酶A的情况下与[14C]棕榈酰辅酶A孵育，或者脑干和脊髓切片与[3H]棕榈酸孵育时，在出生后第20天的震颤小鼠中也观察到PLP的脂肪酰化降低。髓鞘中脂肪酸：辅酶A连接酶的活性降低。这些数据表明，震颤小鼠髓鞘中PLP酰化降低可能是由于脂肪酸激活和转移到PLP中的活性降低，并且髓鞘中存在代谢紊乱，因为PLP的酰化已被证明发生在髓鞘膜中。虽然精神活性物质（200 microM）在体外仅抑制17%的酰化，但它可能是体内PLP酰化降低的原因。
