Neuroserpin, a brain-associated inhibitor of tissue plasminogen activator is localized primarily in neurons - Implications for the regulation of motor learning and neuronal survival

被引:198
作者
Hastings, GA
Coleman, TA
Haudenschild, CC
Stefansson, S
Smith, EP
Barthlow, R
Cherry, S
Sandkvist, M
Lawrence, DA
机构
[1] Amer Red Cross, Jerome H Holland Lab, Dept Biochem, Rockville, MD 20855 USA
[2] Amer Red Cross, Jerome H Holland Lab, Dept Expt Pathol, Rockville, MD 20855 USA
[3] Human Genome Sci Inc, Dept Prot Therapeut, Rockville, MD 20850 USA
[4] Human Genome Sci Inc, Dept Prot Express, Rockville, MD 20850 USA
关键词
D O I
10.1074/jbc.272.52.33062
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A cDNA clone for the serine proteinase inhibitor (serpin), neuroserpin, was isolated from a human whole brain cDNA library, and recombinant protein was expressed in insect cells, The purified protein is an efficient inhibitor of tissue type plasminogen activator (tPA), having an apparent second-order rate constant of 6.2 x 10(5) M-1 s(-1) for the two-chain form. However, unlike other known plasminogen activator inhibitors, neuroserpin is a more effective inactivator of tPA than of urokinase-type plasminogen activator, Neuroserpin also effectively inhibited trypsin and nerve growth factor-gamma but reacted only slowly with plasmin and thrombin, Northern blot analysis showed a 1.8 kilobase messenger RNA expressed predominantly in adult human brain and spinal cord, and immunohistochemical studies of normal mouse tissue detected strong staining primarily in neuronal cells with occasionally positive microglial cells. Staining was most prominent in the ependymal cells of the choroid plexus, Purkinje cells of the cerebellum, select neurons of the hypothalamus and hippocampus, and in the myelinated axons of the commissura, Expression of tPA within these regions is reported to be high and has previously been correlated with both motor learning and neuronal survival, Taken together, these data suggest that neuroserpin is likely to be a critical regulator of tPA activity in the central nervous system, and as such may play an important role in neuronal plasticity and/or maintenance.
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页码:33062 / 33067
页数:6
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