ABSTRACT
It is known that blood serum proteins of tumorbearing mice display tumorspecific activity. However, to date, the nature of this activity has remained elusive, and no tumorspecific proteins have been detected in the blood serum of tumorbearing animals compared with those in healthy animals. The present study postulated and investigated the hypothesis that the observed tumorspecific activity of the blood serum proteins is not associated with the appearance of novel serum proteins but with changes in the conformation of the existing ones. The present study showed conformational changes of two serum albumin proteins and interαtrypsin inhibitor heavy chain 4 (ITIH4) in mice with B16 melanoma compared to tumorfree mice, as determined by differences in the products of proteolysis by proteomic analysis following column chromatography. The differences in the conformation of serum albumin in mice with B16 melanoma and tumorfree mice were accompanied by a change in the interaction of these molecules with the fatty acid spin probe 16doxyl stearic acid. The differential conformation of ITIH4 in mice with B16 melanoma and that in tumorfree mice was accompanied by inhibition of tumor growth and increased life span. Analysis of the role of proteaseantiproteases (serpins) in the serum of tumorbearing animals in tumor growth confirmed the hypothesis that tumor growth in the body is mediated, at least in part, via balancing of serpins.
Subject(s)
Biomarkers, Tumor/blood , Calcium-Binding Proteins/blood , Glycoproteins/blood , Melanoma, Experimental/blood , Animals , Biomarkers, Tumor/chemistry , Calcium-Binding Proteins/chemistry , Cell Line, Tumor , Glycoproteins/chemistry , Male , Melanoma, Experimental/pathology , Mice, Inbred C57BL , Neoplasm Transplantation , Protein Conformation , Proteinase Inhibitory Proteins, Secretory , Proteolysis , Serum Albumin/chemistry , Serum Albumin/metabolism , Trypsin/chemistry , Tumor BurdenABSTRACT
The aim was to ascertain any possible linkage between humoral immune responses to principal biomarkers (α-synuclein monomers, its toxic oligomers or fibrils, dopamine and S100B) and cellular immunity in Parkinson's disease development. There were elevated autoantibody titers to α-synuclein monomers, oligomers plus fibrils in 72%, 56%, and 17% of Parkinsonian patients respectively with a 5-year disease duration. Additionally, there were increased titers to dopamine and S100B (96% and 89%) in the 5-year patient group. All of these values subsided in 10-year sufferers. Furthermore, CD3+, CD4+, CD8+ T-lymphocyte and B-lymphocyte subsets declined in the patient cohort during Parkinsonism indicating disease associated reductions in these lymphocyte subsets.
