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

M. W.C. Hatton; B. Ross; S. M.R. Southward; A. Lucas

doi:10.1053/meta.2000.17666

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

M. W.C. Hatton, B. Ross, S. M.R. Southward, A. Lucas

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

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 ¹²⁵I-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 close was increased 35-fold from 0.11 μg/kg to 3.8 μg/kg. The fractional distribution of SERP-1 between the intravascular (0.21), noncirculating vascular wall (0.09), and extravascular compartments (0.70) at equilibrium did not change significantly over this close 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.

Original language	English (US)
Pages (from-to)	1449-1452
Number of pages	4
Journal	Metabolism: Clinical and Experimental
Volume	49
Issue number	11
DOIs	https://doi.org/10.1053/meta.2000.17666
State	Published - 2000
Externally published	Yes

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Endocrinology

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

abstract = "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 125I-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 close was increased 35-fold from 0.11 μg/kg to 3.8 μg/kg. The fractional distribution of SERP-1 between the intravascular (0.21), noncirculating vascular wall (0.09), and extravascular compartments (0.70) at equilibrium did not change significantly over this close 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.",

author = "Hatton, {M. W.C.} and B. Ross and Southward, {S. M.R.} and A. Lucas",

note = "Funding Information: From the Department of Pathology and Molecular Medicine, McMaster University Health Sciences Centre, Hamilton, Ontario; and the John P. Robarts Research Institute, University of Western Ontario, London, Ontario, Canada. Submitted December 21, 1999; accepted April 9, 2000. Supported by a Grant-in-Aid from the Heart and Stroke Foundation of Ontario. Address reprint requests to Mark W.C. Hatton, PhD, Department of Pathology and Molecular Medicine (HSC-4N67), McMaster University Health Sciences Centre, 1200 Main St W, Hamilton, Ontario L8N 3Z5. Copyright r 2000 by W.B. Saunders Company 0026-0495/00/4911-0004$10.00/0 doi:10.1053/meta.2000.17666",

year = "2000",

doi = "10.1053/meta.2000.17666",

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AU - Hatton, M. W.C.

AU - Ross, B.

AU - Southward, S. M.R.

AU - Lucas, A.

N1 - Funding Information: From the Department of Pathology and Molecular Medicine, McMaster University Health Sciences Centre, Hamilton, Ontario; and the John P. Robarts Research Institute, University of Western Ontario, London, Ontario, Canada. Submitted December 21, 1999; accepted April 9, 2000. Supported by a Grant-in-Aid from the Heart and Stroke Foundation of Ontario. Address reprint requests to Mark W.C. Hatton, PhD, Department of Pathology and Molecular Medicine (HSC-4N67), McMaster University Health Sciences Centre, 1200 Main St W, Hamilton, Ontario L8N 3Z5. Copyright r 2000 by W.B. Saunders Company 0026-0495/00/4911-0004$10.00/0 doi:10.1053/meta.2000.17666

PY - 2000

Y1 - 2000

N2 - 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 125I-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 close was increased 35-fold from 0.11 μg/kg to 3.8 μg/kg. The fractional distribution of SERP-1 between the intravascular (0.21), noncirculating vascular wall (0.09), and extravascular compartments (0.70) at equilibrium did not change significantly over this close 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.

AB - 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 125I-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 close was increased 35-fold from 0.11 μg/kg to 3.8 μg/kg. The fractional distribution of SERP-1 between the intravascular (0.21), noncirculating vascular wall (0.09), and extravascular compartments (0.70) at equilibrium did not change significantly over this close 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.

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JO - Metabolism: Clinical and Experimental

JF - Metabolism: Clinical and Experimental

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ER -

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

Abstract

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