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Biomedical subjects

P Z Khasigov

Publications and source records attributed to P Z Khasigov.

At least 19 recordsLinked to original sources

Role of matrix metalloproteinases and their inhibitors in tumor invasion and metastasis.

The role of various matrix metalloproteinases (MMP)--such as gelatinases, stromelysins, matrilysin, collagenase-3, and membrane-bound MMP (MB-MMP)--in tumor invasion and metastasis is discussed. Data suggesting significance for malignant growth of the expression level of these enzymes and also of their activators and inhibitors are presented. It is concluded that at different stages of tumor progression the activity of different MMPs is displayed, which is regulated by various growth factors and oncogenes. Different malignancies are characterized by changes in activities of specific MMPs. Data are presented which show significance of the ratio between the MMP activity and that of tissue inhibitors of metalloproteinases (TIMP) in tumor invasion and metastasis, especially in connection with a dual role of TIMP as both MMP inhibitors and activators.

Humans↗

Matrix metalloproteinases of normal human tissues.

This review considers biochemical properties of the family of matrix metalloproteinases (MMPs) of normal human tissues and the involvement of these enzymes in morphogenesis. Four main MMP subfamilies are characterized, and a group of other MMPs is described. Data on mechanisms of activation and inhibition of MMPs in certain tissues during various physiological processes (embryogenesis, angiogenesis, tissue growth and involution) are considered. Information about tissue inhibitors of MMP is presented, and the ability of these inhibitors to regulate the activity of MMPs is analyzed.

Humans↗

Role of matrix metalloproteinases in development of diabetic nephropathy.

This review considers molecular mechanisms that underlie disorders in the structure and metabolism of renal extracellular matrix in diabetic nephropathy. The contribution of the increased synthesis of renal extracellular matrix proteins in the accumulation of renal mesangial matrix is considered, and the important role of the degradation system of the extracellular matrix proteins in the development of fibrosis is also shown. Data on changes in mRNA expression for the matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) in various forms of diabetic nephropathy are presented. A correlation is established between changes in the balance of MMP proteolytic activity and TIMP activity and the accumulation of extracellular matrix.

Diabetic Nephropathies↗

Standardized and extended catalog of major proteins of the human kidney.

A new version of a two-dimensional electrophoretic catalog of proteins of the human kidney and of various morphological and functional structures of the human kidney is presented; it contains information about 179 polypeptides. The following proteins were identified: crystallin, albumin, mitochondrial superoxide dismutase, actin, fatty acid-binding protein, alpha-ATP-synthase, and transferrin. Some protein groups are specific for certain morphological structures.

Amino Acid Sequence↗

[Basal membrane proteins].

The review summarizes recent achievements in biochemistry of basal lamina which is highly specialized structural element of extracellular matrix. Structural and functional characteristics of main basal lamina proteins are reviewed including collagen type IV, laminin, nidogen, and heparan sulfate-containing proteoglycans. Special attention is paid to characteristics of structure and biochemical composition of renal glomerular basal lamina which is one of the main components of renal filtration barrier. Possible methods of investigation and characterization of new basal lamina proteins are discussed which help in understanding of biochemical composition of this structure.

Basement Membrane↗

[Mapping proteins from various structural regions of human kidney by two-dimensional electrophoresis].

The protein composition of various structural divisions of human kidney was studied using two-dimensional electrophoresis. Two-dimensional electrophoregrams of the cortical substance of human kidney revealed 165 polypeptide fractions within the pH range of 4.5-7.5, having molecular masses of 10 to 330 kDa. Electrophoresis of glomerular proteins gave 155 fractions with M(r) = 15-300 kDa, whereas fractionation of glomerular basement membrane proteins gave 40 fractions with M(r) = 30-330 kDa within the same range of pH. The M(r) values for all fractions and the relative electrophoretic mobility in the forward direction were determined. A comparative analysis of the electrophoregrams was conducted. The data obtained were used to construct two-dimensional maps of the cortical substance and glomerular proteins of human kidney.

Electrophoresis, Gel, Two-Dimensional↗

The role of isoacceptor transfer RNAs in regulation of age-related changes in the rate of protein synthesis.

In cell-free protein-synthesizing systems containing an S30 extract from liver and brain cortex tissues of 22-day-old fetuses and of male WAG rats (1-900 days old), the minimal rate of protein synthesis was observed in the fetuses, while the maximal one - in 7-day-old animals. The difference in the rates of protein synthesis correlated with the minimal concentration of total tRNA in the former group and with its maximal concentration in the latter. In fetal tissues, an addition to cell-free systems of total tRNA isolated from homologous tissues of 7-day-old animals augmented protein synthesis up to a level observed in 7-day-old animals, whereas in the tissues of animals belonging to other age groups total tRNA had a far less pronounced stimulating effect which decreased with age. Fractionation of total tRNA and analysis of effects of individual tRNAs on protein synthesis demonstrated that the stimulating influence was induced by tRNA(2Arg), tRNA(4Arg) and tRNA(2Val) from brain cortex and by tRNA(2Leu), tRNA(5Leu), tRNA(2Val), tRNA(1Met) and tRNA(2Met) from liver.

Aging↗

Age-related changes in the rates of polypeptide chain elongation.

The time of an average polypeptide chain synthesis, ts, in the liver and brain cortex of rats of various age--from the 17th day of prenatal life up to the 24th month of the postnatal period--was estimated. At the end of the prenatal period the value of t is much higher than in postnatal life. In newborns, the t value is minimal, showing a gradual increase during the postnatal development. Determination of an average molecular mass of newly synthesized polypeptides demonstrated that the increase of t in postnatal life is due to the decrease of the rate of polypeptide chain elongation.

Aging↗

Effect of Zajdela ascites hepatoma on the activity and synthesis of liver histidase of tumor-bearing rats.

The synthesis of histidase occurs only in free polyribosomes. The relative content of histidase synthesizing polyribosomes in rat liver, in Zajdela ascites hepatoma cells and in the liver of tumor-bearing rats is equal to 1.35%, 0.11% and 0.57%, respectively (of the total amount of free polyribosomes). It was found that hepatoma cell sap has an inhibitory effect on the synthesis of proteins in the cell-free system reconstructed from polyribosomes and cell sap of control rats.

Ammonia-Lyases↗

A three-stage chromatographic procedure for cordycepin. Quantitative estimation in rat brain tissue.

A technique for the quantitative estimation of intraperitoneally injected unlabelled cordycepin in the acid soluble pool (ASP) isolated from rat brain tissue has been suggested. It consists of consecutive chromatography of ASP on columns of Dowex 1 X 8, Dihydroxyboryl-SP500 and Sephasorb-HP. As a result, the fraction containing 2'-deoxyriboadenosine and 3'-deoxyriboadenosine (cordycepin) was isolated from the brain tissue ASP of experimental animals which were given a cordycepin injection. The 2'-deoxyriboadenosine fraction was isolated from tissue ASP of control animals which were not given an injection of this antibiotic. Brain tissue antibiotic content was estimated by the difference in mumolar nucleosides quantity values in the two fractions (control/experiment).

Animals↗

Quantitative estimate of unlabelled cordycepin in acid-soluble pool isolated from rat brain tissue after intraperitoneal injection of the inhibitor.

A technique for the quantitative estimation of intraperitoneally injected unlabelled cordycepin in an acid-soluble pool (ASP) isolated from rat brain tissue is suggested. It consists in consecutive chromatography of ASP on Dowex 1 X 8, Dihydroxyboryl = SP500 and Sephasorb-HP. The fraction containing 2'-deoxyriboadenosine and 3'-deoxyriboadenosine (cordycepin) has been isolated from brain tissue ASP of experimental animals after a cordycepin injection. 2'-Deoxyriboadenosine fraction has been isolated from tissue ASP of the control animals not subjected to an inhibitor injection. Brain tissue antibiotic content has been estimated by the difference in nucleoside quantity values (microM) in these two fractions (control/experiment).

Animals↗

[Dependence of cordycepin inhibition of heterogeneous nuclear RNA biosynthesis in rat brain on the size of the poly(A) segments].

A study was made of the effect of cordicepin on the biosynthesis of rat brain heterogeneous nuclear RNA (hnRNA) fractions, such as poly(A-)hnRNA, oligo(A+)hnRNA and poly(A+)hnRNA differing in the size of poly(A)-segments. Cordicepin was shown to inhibit the biosynthesis of poly(A+)hnRNA alone. However, small doses of the antibiotic do not virtually inhibit the biosynthesis of hnRNA with shorter segments of poly(A). At the same time they inhibit the biosynthesis of hnRNA containing long chains of poly(A) in the 3'-end. A possible molecular mechanism of the phenomenon reviewed is under discussion.

Animals↗

[Metabolism of poly(A+)mRNA during ontogenesis: changes in half-life and processing time in rat brain cortical cells].

The values of half-life (t 1/2) and processing (to) time of poly(A+) mRNA were calculated from the kinetics of label accumulation by free and membrane-bound polyribosomes of brain cortical cells of 1-, 7-, 30-, 180-, 360-, 540-, and 720-day-old rats and of 17- and 21-day-old embryos. The membrane-bound polyribosomes contain only one class of poly(A+) mRNA, whereas the free ones--predominantly two classes. The most pronounced changes in poly(A+) mRNA metabolism are observed in the case of free polyribosomes. It was found that poly(A+) mRNA of both polyribosomal classes is generally stabilized during late embryogenesis and neonatal period, after which the values of t 1/2 are decreased, showing a drastic fall upon ageing. The changes in to are inversely related to those of t 1/2. Free polyribosomes, beginning with the 30th postnatal day, reveal a short-living rapidly turned over poly(A+) mRNA, whose parameters remain practically unchanged throughout the ontogenesis period under study.

Aging↗

[Modification of the half-life of poly (A+)mRNA in liver and brain cells of the rat during embryogenesis and postnatal development].

The poly(A+)/poly(A-)mRNA ratio and the half-life time of poly(A+)mRNA for mRNA metabolism in the liver and brain of rat in the course of ontogensis, late embryogenesis, postnatal development and upon ageing were determined. It was shown that in the course of ontogenesis both the ratio of poly(A+)/poly(A-)mRNA of free and membrane-bound polyribosomes and the half-life time of poly(A+)mRNA determined from the degradation kinetics in the presence of actinomycin D are changed. A possible role of poly(A) sequences in the regulation of mRNA life-time is discussed.

Aging↗