ABSTRACT
Bioactive aldehydes are among main factors of proteins postsynthetic modifications, which are the cause and consequence of many diseases. Comparative study of some aldehydes modifying action on gelatin was carried out in vitro. Gelatin samples (20 mM) were incubated with: ribose, deoxyribose, glyoxal, methylglyoxal, formaldehyde, acrolein (20 mM each) and their combinations in 0.1 M Naphosphate buffer (pH 7.4) containing 0.02% sodium azide at 37 °C in the dark for 30 days. We investigated the fluorescent properties of these samples and their molecular weight distribution by electrophoresis. It has been revealed that formed adducts had different fluorescence spectra. According to fluorescence intensity these aldehydes were put in order: formaldehyde < methylglyoxal < acrolein Subject(s)
Cross-Linking Reagents/chemistry
, Gelatin/chemistry
, Acrolein/chemistry
, Biomimetic Materials
, Buffers
, Collagen/chemistry
, Deoxyribose/chemistry
, Fluorescence
, Formaldehyde/chemistry
, Glyoxal/chemistry
, Hydrogen-Ion Concentration
, Pyruvaldehyde/chemistry
, Ribose/chemistry
, Solutions
, Spectrometry, Fluorescence
ABSTRACT
Experiments were carried out on rats with lathyrism, which was induced by adding semicarbazide (0.075%) into drinking water for 45 days. The data obtained show a 30% reduction in the body weight and an increase in.organ weight coefficients. Semicarbazide intake led to the pelvic limb paralysis, scoliosis, bone tissue degradation, cartilage growth, 46% decrease of the calcium level in the femur. It has been detected essential structural changes in extracellular matrix based on the collagen cross-links reduction. The activity of lysyl oxidase, a key enzyme for the collagen development, showed 5-fold decrease in the aorta tissues. The level of formaldehyde, a nonenzymic cross-links developer, has been measured in the liver tissue by the aldehyde trap (5,5-dimethyleyclohexane-1,3-dione) administration and then fluorimetric determination of formaldimedone. Under semicarbazide load, the formaldehyde level in the liver tissue was reduced by 47%. Therefore, semicarbazide influences not only the enzymic development of aldehyde groups in collagen, but the level of other aldehydes, which can cause cross-links. This experimental model of lathyrism is appropriate for investigation of the lysyl oxidase inhibitors effect on extracellular matrix.
Subject(s)
Collagen/metabolism , Disease Models, Animal , Lathyrism/metabolism , Protein-Lysine 6-Oxidase/metabolism , Animals , Aorta, Thoracic/enzymology , Aorta, Thoracic/metabolism , Body Weight , Bone and Bones/enzymology , Bone and Bones/metabolism , Formaldehyde/metabolism , Joints/enzymology , Joints/metabolism , Lathyrism/chemically induced , Lathyrism/enzymology , Male , Organ Size , Rats , Rats, Wistar , Semicarbazides/pharmacology , Skin/enzymology , Skin/metabolismABSTRACT
On the basis of complex approach to bone and haematopoetic tissue interaction the authors studied the influence of low weight metabolites on stromal fibroblasts and components of extacellular matrix of bone and skin (collagen and glycosaminoglycans). Specificity of different metabolites action on physico-chemical abilities of type I collagen, amino acid composition changes, surface charge, ratio of alpha- and beta-compounds, BrCN-fragments of alpha-1 component cross-links was shown. The dose dependence of formiate effect on processes of proteins glycosilation, cross-linking in bone and cartilage connective tissue and serum glycoproteins was established. The results obtained showed sensitivity of the bone tissue exstacellular matrix to influence of low-weight metabolites action at the level of post-synthetic modification of its components, their intermolecular interaction and process of osteogenesis.
Subject(s)
Amino Acids/metabolism , Connective Tissue/metabolism , Extracellular Matrix/metabolism , Stromal Cells/metabolism , Animals , Bone Marrow Cells/metabolism , Bone and Bones/cytology , Bone and Bones/drug effects , Bone and Bones/metabolism , Cells, Cultured , Collagen Type I/metabolism , Connective Tissue/drug effects , Fibroblasts/metabolism , Formates/pharmacology , Glycoproteins/blood , Glycosaminoglycans/metabolism , Humans , Leukemia/metabolism , Male , Mice , Mice, Inbred Strains , Osteogenesis/physiology , Rats , Rats, Wistar , Skin/cytology , Skin/drug effects , Skin/metabolism , Stromal Cells/cytology , Stromal Cells/drug effectsABSTRACT
Acetic and succinate acids KoA acyl derivatives interacting with formate were displayed to produce alpha-ketoacids--pyruvate and alpha-ketoglutarate. These acids also interact with formate and make pyruvic and malate acids, while alpha-ketoglutarate, evidently, tricarboxy acids. Interaction of formate with acetic and succinate acids inspite of occurring out of the tricarbone cycle increases the latter metabolic functions.
