Biomedical subjects

Vadim T Ivanov

Publications and source records attributed to Vadim T Ivanov.

8 recordsLinked to original sources

PubMed2007

Stimulation of fibroblast proliferation by neokyotorphin requires Ca influx and activation of PKA, CaMK II and MAPK/ERK.

Neokyotorphin [TSKYR, hemoglobin alpha-chain fragment (137-141)] has previously been shown to enhance fibroblast proliferation, its effect depending on cell density and serum level. Here we show the dependence of the effect of neokyotorphin on cell type and its correlation with the effect of protein kinase A (PKA) activator 8-Br-cAMP, but not the PKC activator 4beta-phorbol 12-myristate, 13-acetate (PMA). In L929 fibroblasts, the proliferative effect of neokyotorphin was suppressed by the Ca2+ L-type channel inhibitors verapamil or nifedipine, the intracellular Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester, kinase inhibitors H-89 (PKA), KN-62 (Ca2+/calmodulin-dependent kinase II) and PD98059 (mitogen-activated protein kinase). The proliferative effect of 8-Br-cAMP was also suppressed by KN-62 and PD98059. PKC suppression (downregulation with PMA or inhibition with bisindolylmaleimide XI) did not affect neokyotorphin action. The results obtained point to a cAMP-like action for neokyotorphin.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed2005

Antitumor effect of valorphin in vitro and in vivo: combined action with cytostatic drugs.

The action of the cytostatic drugs (epirubicin and vincristine) in combination with the endogenous antiproliferative beta-hemoglobin fragment (33-39), valorphin, was studied in tumor (L929 and A549) cell cultures, primary culture of murine bone marrow cells and in murine model of breast carcinoma in vivo. Simultaneous application of 1 microM valorphin and 1 microM epirubicin, in vitro, did not result in an additive suppressive effect on cell culture growth. Additive effects were achieved with alternating applications of the peptide and the drugs, namely, 0.5 microM (but not 1 microM) epirubicin added 24 h prior to 1 microM valorphin; 1 microM valorphin added 48 h prior to 0.1 microM epirubicin, or 0.1 microM vincristine, or 0.05 microM vincristine, which resulted in 100% cell death in the both series with vincristine and up to 78% cell biomass reduction in the experiments with epirubicin. In the in vivo model (female BLRB mice with subcutaneously inoculated syngeneic mammary carcinoma), simultaneous treatment with 25 mg/m(2) epirubicin and 1 mg/kg valorphin resulted in 42% of tumor growth inhibition, as compared with the negative control group and 22% inhibition as compared with the epirubcin-treated group (at 20th day of treatment). Survival was significantly improved (69% compared to 39% in the group treated with epirubicin only) at day 26 after the treatment beginning.

Adamantane↗

PubMed2005

Generation of peptides by human erythrocytes: facts and artifacts.

Previously reported data on peptide composition of human erythrocyte lysate were obtained under conditions that did not exclude proteolytic degradation of hemoglobin in the process of peptide isolation. Comparative chromatographic analysis of the diluted erythrocyte lysate incubated in acidic conditions with or without proteolytic enzyme inhibitors showed that several peptides earlier identified as intraerythrocyte ones in fact result from hemoglobin degradation by erythrocyte acidic protease(s) during incubation of the lysate. A rational scheme excluding postlysis proteolysis was developed for isolation of peptide fraction. Further analysis resulted in determination of structure and content of about 50 endogenous intraerythrocyte hemoglobin fragments. A primary endopeptidase splitting of alpha- and beta-globin chains followed by consecutive exopeptidase trimming of primary fragments is suggested as a degradation mechanism. The intraerythrocyte peptides were shown to differ from peptides excreted by the erythrocytes to the extracellular medium in the primary culture. It was also found that intraerythrocyte peptides cannot play the role of precursors of hemoglobin fragments present in tissue extracts.

Amino Acid Sequence↗

PubMed2005

Peptidomics: a logical sequel to proteomics.

Rapid progress of separation techniques as well as methods of structural analysis provided conditions in the past decade for total screening of complex biologic mixtures for any given class of biomolecules. The present review updates the reader with the modern state of peptidomics, a chapter of chemical biology that deals with structure and biologic properties of sets of peptides present in biologic tissues, cells or fluids. Scope and limitations of currently employed experimental techniques are considered and the main results are outlined. Considerable attention will be afforded to the biologic role of peptides formed in vivo by proteolysis of nonspecialized precursor proteins with other well-defined functions. In conclusion, the connection is discussed between peptidomics and the much more mature and still closely related field of proteomics.

Animals↗

PubMed2003

What to synthesize? From Emil Fischer to peptidomics.

The driving forces, incentives and strategic targets of peptide synthesis have undergone considerable evolution during the centenary following the pioneer work of Emil Fischer. In those days peptide synthesis was considered as a way of confirming the polypeptide theory of protein structure. The scientific community also expected (naively) that the synthesis would eventually lead to the creation of artificial living organisms. Only in the 1950s, when the first exact amino acid sequences were established did peptide chemistry obtain firmer ground and clearly defined targets. The total synthesis of peptide hormones and antibiotics became possible, providing valuable material for elucidating structure-functional relationships and the mechanisms of biological action. In the following years the number of peptides isolated from various biological sources grew with impressive speed and peptides became known as the most abundant, ubiquitous group of low molecular bioregulators. The design and synthesis of novel peptide based pharmaceuticals became an important area of peptide chemistry. At present we are facing the challenge of analysing the structures and bioactivities of total sets of peptides, i.e. peptidoms, present in concrete tissues or groups of cells. The results obtained along these lines at the IBCH RAS Institute of Bioorganic Chemistry are briefly considered in the review.

Amino Acid Sequence↗

PubMed2003

Effect of delta-sleep inducing peptide-containing preparation Deltaran on biomarkers of aging, life span and spontaneous tumor incidence in female SHR mice.

From the age of 3 months until their natural deaths, female Swiss-derived SHR mice were subcutaneously injected 5 consecutive days every month with 0.1 ml of normal saline (control) or with 2.5 microg/mouse (approximately 100 microg/kg) of delta-sleep inducing peptide (DSIP, Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu) as the preparation Deltaran solved in 0.1 ml of saline. There were 54 mice in each group. The results of this study show that the treatment with Deltaran did not influence food consumption, but decreased the body weight of mice; it slowed down the age-related switching-off of estrous function; it decreased by 22.6% the frequency of chromosome aberrations in bone marrow cells; it did not influence mean life span; and it increased by 17.1% life span of the last 10% of the survivors and by 24.1% maximum life span in comparison with the control group. We also found that treatment with Deltaran significantly decreased total spontaneous tumor incidence (by 2.6-fold), mainly mammary carcinomas and leukemias in mice as compared with the control group. This is the first report on geroprotector and anticarcinogenic effect of DSIP-containing preparation Deltaran.

Aging↗

PubMed2003

Proliferative activity of neokyotorphin-related hemoglobin fragments in cell cultures.

alpha-Hemoglobin fragments alpha-(133-141), alpha-(134-141), alpha-(135-141), alpha-(137-141), alpha-(134-140), alpha-(133-138), alpha-(134-140) and alpha-(137-138) stimulate L929 tumor cell proliferation, alpha-(134-141) being the most active. alpha-(134-141) stimulates proliferation of M3 melanoma cells, murine embryonic fibroblasts, primary cultures of red bone marrow and spleen cells. In L929 cells the effect of alpha-(134-141) is cell density independent; in M3 cells alpha-(137-141) and alpha-(134-141) are most active at density 10,000 cells/well (96 well plate) independently on FBS content.

Animals↗

PubMed2002

Family of hemorphins: co-relations between amino acid sequences and effects in cell cultures.

Hemorphins, i.e. endogenous fragments of beta-globin chain segment (32-41) LVVYPWTQRY(F) suppress the growth of transformed murine fibroblasts L929 cell culture, the effect is due to cytotoxicity and inhibition of cell proliferation. The contribution of cytotoxicity depends on the presence of Leu(32): VV-hemorphins, except VV-hemorphin-4, exhibit cytotoxicity significantly higher than respective LVV-hemorphins. Decrease of cell number induced by hemorphins depend on the extent of N- and C-terminal degradation of hemorphins: VV-hemorphins in most cases are more active than LVV-, V-hemorphins, and hemorphins. In the group of VV-hemorphins the activity of VV-hemorphin-5 (valorphin) is significantly higher than of VV-hemorphin-7, VV-hemorphin-6, and VV-hemorphin-4, meaning that the presence of C-terminal Gln is important for suppressing of cell number. The amino acid sequence VVYPWTQ corresponding to valorphin was identified as important for manifestation of the both cytotoxic and antiproliferative effects.

Amino Acid Sequence↗