Altered clearance of human alpha 2-macroglobulin complexes following reaction with cis-dichlorodiamineplatinum(II).

Published

Journal Article

Clearance studies were performed in mice using alpha 2-macroglobulin (alpha 2M), alpha 2M-trypsin complex and alpha 2M-CH3NH2 complex. All three species were incubated with cis-dichlorodiamine platinum(II) (cis-DDPt) at concentrations between 9.0 microM and 1.67 mM for 4 h and then dialyzed. The clearance rate of native alpha 2M was unchanged following incubation with cis-DDPt. alpha 2M-trypsin and alpha 2M-CH3NH2 cleared rapidly from the circulation; however, reaction with cis-DDPt significantly decreased the plasma elimination rate of both complexes. Non-denaturing gel electrophoresis and alpha 2M activity assays demonstrated relative stability following incubations with cis-DDPt which markedly altered clearance. Evidence for cis-DDPt crosslinking of alpha 2M subunits was obtained; however, whether this crosslinking is involved in altered clearance remains undetermined. Iodoacetamide treatment of alpha 2M did not duplicate the effect of cis-DDPt on alpha 2M clearance, nor did it inhibit the effect of cis-DPPt on alpha 2M clearance. Plasma elimination of alpha 2M complex was also unaltered by pretreatment of mice with intravenous free cis-DDPt.

Full Text

Duke Authors

Cited Authors

  • Gonias, SL; Pizzo, SV

Published Date

  • December 4, 1981

Published In

Volume / Issue

  • 678 / 2

Start / End Page

  • 268 - 274

PubMed ID

  • 6172155

Pubmed Central ID

  • 6172155

International Standard Serial Number (ISSN)

  • 0006-3002

Digital Object Identifier (DOI)

  • 10.1016/0304-4165(81)90216-6

Language

  • eng

Conference Location

  • Netherlands