Metabolism and distribution of the virus-encoded serine proteinase inhibitor SERP-1 in healthy rabbits

Metabolism and distribution of the virus-encoded serine proteinase inhibitor SERP-1 in healthy rabbits
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DOI:
10.1053/meta.2000.17666
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发表时间:
2000-11-01
影响因子:
9.8
通讯作者:
Lucas, A
Lucas, A
中科院分区:
医学1区
文献类型:
--
作者:
Hatton, MWC;Ross, B;Lucas, A

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SERP-1是丝氨酸蛋白酶抑制剂(“serpin”)家族的分泌型粘液瘤病毒编码的55-kd蛋白,其强烈抑制动脉中膜平滑肌细胞的有丝分裂,从而防止损伤的兔和大鼠动脉中的狭窄。在健康家兔的循环中注射不同剂量的I-125-SERP-1,测定了其分解率(FCR)和房室分布。当剂量从0.11 mug/kg增加到3.8 mug/kg时,血管内空间的FCR从2.99 d(-1)降低到2.39 d(-1),全身FCR从0.66 d(-1)降低到0.51 d(-1)。在该剂量范围内,平衡时SERP-1在血管内(0.21)、非循环血管壁(t0.09)和血管外室(0.70)之间的分数分布没有显著变化。SERP-1似乎没有选择性地积累在任何器官中的11只兔子超过6天的时间间隔研究。与其他兔血浆丝氨酸蛋白酶抑制剂相比,SERP-1在体内的行为最接近肝素辅因子II的行为。Copyright(C)2000 by W.B.桑德斯公司
SERP-1 is a secreted myxoma virus-encoded 55-kd protein of the serine proteinase inhibitor ("serpin") family that strongly inhibits the mitosis of medial arterial smooth muscle cells, thus preventing stenosis in injured rabbit and rat arteries. We have measured the fractional catabolic rate (FCR) and compartmental distribution of I-125-SERP-1 after injection of various doses into the circulation of healthy rabbits. The FCR within the intravascular space decreased from 2.99 d(-1) to 2.39 d(-1) and the whole-body FCR decreased from 0.66 d(-1) to 0.51 d(-1) as the dose was increased 35-fold from 0.11 mug/kg to 3.8 mug/kg. The fractional distribution of SERP-1 between the intravascular (0.21), noncirculating vascular wall t0.09), and extravascular compartments (0.70) at equilibrium did not change significantly over this dose range. SERP-1 did not appear to selectively accumulate in any organ in any of 11 rabbits studied over a 6-day interval. In comparison to other rabbit plasma serpins, the behavior of SERP-1 in vivo most closely resembled that of heparin cofactor II. Copyright (C) 2000 by W.B. Saunders Company.