Abstract

The primary objective of the laboratory is the study of protease regulation in the circulation, a process primarily mediated by binding of protease to inhibitors followed by clearance from the circulation. Studies this year have involved clearance of (1) alpha-macroglobulin (alpha 2-M) complexes with trypsin, thrombin and plasmin as well as with methylamine (MeNH2) which alters alpha 2-M in a manner analogous to proteases; (2) antithrombin III (At III) complexes with thrombin. Moreover, during the current year, the laboratory has begun studying the in vitro binding of alpha 2-M complexes to macrophages since the route of clearance of complexes from the circulation is via the reticulo-endothelial system (RES). Recently, the applicant has begun a series of studies with cis-dichloro-diameplatinum (II) (cis-DDP) and alpha 2-M. These studies were undertaken since cis-DDP is an important antitumor drug which possesses two amine groups. It was felt that cis-DDP might react with alpha 2-M in a manner analogous to MeNH2.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL024066-13
Application #
3337492
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1979-07-01
Project End
1992-06-30
Budget Start
1991-07-01
Budget End
1992-06-30
Support Year
13
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
Duke University
Department
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705

  Publications

Gonzalez-Gronow, Mario; Cuchacovich, Miguel; Francos, Rina et al. (2010) Antibodies against the voltage-dependent anion channel (VDAC) and its protective ligand hexokinase-I in children with autism. J Neuroimmunol 227:153-61
Jockheck-Clark, Angela R; Bowers, Edith V; Totonchy, Mariam B et al. (2010) Re-examination of CD91 function in GRP94 (glycoprotein 96) surface binding, uptake, and peptide cross-presentation. J Immunol 185:6819-30
Misra, Uma Kant; Mowery, Yvonne; Kaczowka, Steven et al. (2009) Ligation of cancer cell surface GRP78 with antibodies directed against its COOH-terminal domain up-regulates p53 activity and promotes apoptosis. Mol Cancer Ther 8:1350-62
Benvegnu, Stefano; Franciotta, Diego; Sussman, Josh et al. (2009) Prion protein paralog doppel protein interacts with alpha-2-macroglobulin: a plausible mechanism for doppel-mediated neurodegeneration. PLoS One 4:e5968
Bowers, Edith V; Horvath, Jeffrey J; Bond, Jennifer E et al. (2009) Antigen delivery by alpha(2)-macroglobulin enhances the cytotoxic T lymphocyte response. J Leukoc Biol 86:1259-68
Misra, U K; Wang, F; Pizzo, S V (2009) Transcription factor TFII-I causes transcriptional upregulation of GRP78 synthesis in prostate cancer cells. J Cell Biochem 106:381-9
Gonzalez-Gronow, Mario; Kaczowka, Steven; Gawdi, Govind et al. (2008) Dipeptidyl peptidase IV (DPP IV/CD26) is a cell-surface plasminogen receptor. Front Biosci 13:1610-8
Misra, Uma K; Kaczowka, Steven; Pizzo, Salvatore V (2008) The cAMP-activated GTP exchange factor, Epac1 upregulates plasma membrane and nuclear Akt kinase activities in 8-CPT-2-O-Me-cAMP-stimulated macrophages: Gene silencing of the cAMP-activated GTP exchange Epac1 prevents 8-CPT-2-O-Me-cAMP activation of Akt a Cell Signal 20:1459-70
Lillis, Anna P; Greenlee, Mallary C; Mikhailenko, Irina et al. (2008) Murine low-density lipoprotein receptor-related protein 1 (LRP) is required for phagocytosis of targets bearing LRP ligands but is not required for C1q-triggered enhancement of phagocytosis. J Immunol 181:364-73
Misra, Uma K; Kaczowka, Steven J; Pizzo, Salvatore V (2008) Interaction between TCL1 and Epac1 in the activation of Akt kinases in plasma membranes and nuclei of 8-CPT-2-O-Me-cAMP-stimulated macrophages. Cell Signal 20:130-8

Showing the most recent 10 out of 161 publications