Hemmings S J, Storey K B
Department of Physiology College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Mol Cell Biochem. 1999 Dec;202(1-2):119-30. doi: 10.1023/a:1007069431615.
The characteristics, cellular locus and regulation of the enzyme gamma-glutamyltranspeptidase (gammaGT) in brain were examined. In rat brain homogenates, the activity of the enzyme exhibited tissue differences--kidney>>>brain==testis>>liver>>skeletal muscle=ventricular muscle and regional differences--brain stem>hippocampus=cerebellum>cerebral cortex, with no significant species/strain differences in the select group of mammals studied. Methods were developed for the isolation from brain of microvessels (MV) and plasma membranes from neuronal/glial cells (N/G PM) utilizing morphological indicators and marker analyses. GammaGT activity was >12 higher in MV than N/G PM; however the enzyme displayed: stability, heat-activation and inhibition with maleate to the same extent in both fractions. A comparative study indicated that in the N/G PM fraction, gammaGT activity was low in all animals studied; gammaGT activity in MV however, was barely detectable in amphibians and reptiles, very low in birds and very high in mammal -mirroring the phylogenetic development of a functional blood-brain barrier. In the rat, gammaGT in both MV and N/G PM displayed a pronounced postnatal increase in activity but the extent and the patterns were different--in all cases, that of the MV greatly exceeded that of the N/G PM and in the MV, the enzyme activity the exhibited the same pattern as the postnatal development of the blood-brain barrier. The induction of congenital hypothyroidism by propylthiouracil (PTU) had no effect on gammaGT in N/G PM but effected a one third reduction in the activity of gammaGT in MV. The normalization by thyroid hormone replacement indicated that MVgammaGT is under thyroid hormone control. The induction of hypothyroidism by PTU in the adult, however, was without effect on enzyme activity in either fraction. The implications of the thyroid hormone dependency of MVgammaGT in the neonatal period and the relationship of gammaGT to the function of the blood brain-barrier is discussed.
对大脑中γ-谷氨酰转肽酶（γGT）的特性、细胞定位及调节进行了研究。在大鼠脑匀浆中，该酶的活性表现出组织差异——肾脏＞大脑=睾丸＞肝脏＞骨骼肌=心室肌，以及区域差异——脑干＞海马体=小脑＞大脑皮层，在所研究的特定哺乳动物组中无明显的物种/品系差异。利用形态学指标和标志物分析，开发了从大脑中分离微血管（MV）和神经元/胶质细胞膜（N/G PM）的方法。MV中的γGT活性比N/G PM高12倍以上；然而，该酶在两个组分中均表现出：稳定性、热激活以及被马来酸盐抑制的程度相同。一项比较研究表明，在N/G PM组分中，所研究的所有动物的γGT活性都很低；然而，MV中的γGT活性在两栖动物和爬行动物中几乎检测不到，在鸟类中非常低，而在哺乳动物中非常高——这反映了功能性血脑屏障的系统发育发展。在大鼠中，MV和N/G PM中的γGT在出生后活性均显著增加，但程度和模式不同——在所有情况下，MV的增加幅度大大超过N/G PM，并且在MV中，酶活性与血脑屏障的出生后发育表现出相同的模式。丙硫氧嘧啶（PTU）诱导的先天性甲状腺功能减退对N/G PM中的γGT没有影响，但使MV中γGT的活性降低了三分之一。甲状腺激素替代后的正常化表明，MVγGT受甲状腺激素控制。然而，PTU在成年期诱导的甲状腺功能减退对任何一个组分中的酶活性均无影响。讨论了新生儿期MVγGT对甲状腺激素的依赖性及其与血脑屏障功能的关系。
