Extracellular HspBP1 inhibits formation of a cytotoxic Tag7-Hsp70 complex in vitro and in human serum

Tag7 (PGRP-S) was described as an innate immunity protein. Earlier we have shown that Tag7 forms with Hsp70 a stable complex with cytotoxic and antitumor activity. The same complex is formed in and secreted by cytotoxic T-lymphocytes. We have also found that Hsp-binding protein HspBP1 incapacitates the Tag7-Hsp70 complex. Here we have studied the interaction of extracellular Tag7 and HspBP1. We have shown that HspBP1 binds Tag7 in the conditioned medium of tumor CSML0 cells, thereby preventing formation of the cytotoxic Tag7-Hsp70 complex. We have also found that Tag7, if present in serum (in every third donor on average), is always in complex with HspBP1. This may be a protective measure against indiscriminate attack of the cytotoxic complex on normal cells.     

Polymorphisms of the main genes of neurotransmitter systems: I. The dopaminergic system

The review is focused on the molecular and genetic bases of human personality traits useful for predicting individual performance in sports. Dopamine receptor gene polymorphisms have been found to be associated with novelty seeking, reward dependence, persistence, etc. These facts demonstrate the importance of studies on the contributions of different gene variants characteristic of the dopamine system to the formation of the predisposition of an athlete to success in sports.     

Analysis of a series of significant genetic polymorphisms in athletes

Candidate genes were selected to study genetic polymorphism in athletes. The frequency of the most significant polymorphic variants of genes was determined. In this work, approaches are described to using the findings for developing recommendations on improvement of work capacity during strenuous exercise.     

The heat shock-binding protein (HspBP1) protects cells against the cytotoxic action of the Tag7-Hsp70 complex

Heat shock-binding protein HspBP1 is a member of the Hsp70 co-chaperone family. The interaction between HspBP1 and the ATPase domain of the major heat shock protein Hsp70 up-regulates nucleotide exchange and reduces the affinity between Hsp70 and the peptide in its peptide-binding site. Previously we have shown that Tag7 (also known as peptidoglycan recognition protein PGRP-S), an innate immunity protein, interacts with Hsp70 to form a stable Tag7-Hsp70 complex with cytotoxic activity against some tumor cell lines. This complex can be produced in cytotoxic lymphocytes and released during interaction with tumor cells. Here the effect of HspBP1 on the cytotoxic activity of the Tag7-Hsp70 complex was examined. HspBP1 could bind not only to Hsp70, but also to Tag7. This interaction eliminated the cytotoxic activity of Tag7-Hsp70 complex and decreased the ATP concentration required to dissociate Tag7 from the peptide-binding site of Hsp70. Moreover, HspBP1 inhibited the cytotoxic activity of the Tag7-Hsp70 complex secreted by lymphocytes. HspBP1 was detected in cytotoxic CD8+ lymphocytes. This protein was released simultaneously with Tag7-Hsp70 during interaction of these lymphocytes with tumor cells. The simultaneous secretion of the cytotoxic complex with its inhibitor could be a mechanism protecting normal cells from the cytotoxic effect of this complex.     

Role of the Interchain Interaction Domain of Chain A in Viscumin Cytotoxicity

The sequence coding for the viscumin (mistletoe lectin I, MLI) A-chain (MLA) was cloned from Viscum album genomic DNA with the use of synthetic primers. This yielded three recombinant (r) MLA variants differing in the number of amino acid substitutions. The rMLA structure and properties were probed using monoclonal antibodies against native MLA. Native MLI B-chain (MLB) was shown to facilitate the rMLA folding. Native MLI and chimeric proteins consisting of rMLA and native MLB did not differ in their cytotoxicity toward 3T3 fibroblastoid cells. Residues were identified that are located in the MLB-contacting region and have a considerable effect on the immunochemical and cytotoxic properties of rMLA.     

Genetic and social factors in the development of aggression

The effect of the variants of the serotonin transporter gene (5-HTT) on aggressiveness was studied in male and female control subjects and athletes. Sports were found to generally decrease aggressiveness; this was true both for women doing nonaggressive sports and for men doing combat sports. The control group of men was characterized by higher indices of aggressiveness (physical and verbal aggression, negativism, and suspiciousness) than women were. Women, irrespective of age and whether they participated in sports, exhibited a relationship between 5-HTT gene variants and the displaced aggressiveness and negativism scales: the SS genotype was associated with a higher displaced aggressiveness and a low negativism. Men exhibited a different relationship. The general aggressiveness index was significantly higher in carriers of the LL genotype than in carriers of the SS genotype, whereas these subjects did not differ significantly in the parameters measured by individual scales. In men, the cerebral processes that are presumed to underlie aggressiveness were found to be related to 5-HTT gene variants. The HP component of the cerebral potential responsible for automatic detection of differences was increased and the P3a component responsible for involuntary attention and cognitive control. This suggests that carriers of the SS genotype use more cognitive resources to process information. This may be because the stimulus itself seems to be more “complex,” which results in the involvement of additional resources of the frontal cortex. It may also be assumed that carriers of the SS genotype tend to analyze the incoming information more deeply. This, more “serious” analysis of external information may underlie their refraining from impulsive behavior, which is often aggressive.