elastin and Menkes-Kinky-Hair-Syndrome

Copper is an indispensable trace element for life. Four points are fundamental: copper is combined with essential enzymatic systems (oxidases, transaminases), copper is necessary for inclusion of iron in the molecule of hemoglobin, copper has a primordial role in the metabolism of molecule of hemoglobin, copper has a primordial role in the metabolism of collagen and elastin and some vascular diseases (aneurysms) are closely related to its lack, finally, there is an increase of plasmatic copper during cancerous diseases, which is significant even at an early time and usually proportional to the evolution.

Topics: Anemia, Hypochromic; Animals; Collagen; Copper; Elastin; Hepatolenticular Degeneration; Humans; Menkes Kinky Hair Syndrome; Mice; Neoplasms; Rabbits; Zinc

Several inherited syndromes characterized by abnormal elastic fibers decreased in number and size could be collected under the heading of inherited elastolysis. This morphological concept does not prejudge the causal mechanisms of the elastolysis involving dermis and/or other organs. The elastic fibers anomalies result mainly from elastin crosslinking defects, developmental disturbances or excessive proteolysis.

Topics: alpha 1-Antitrypsin Deficiency; Ehlers-Danlos Syndrome; Elastin; Homocystinuria; Humans; Marfan Syndrome; Menkes Kinky Hair Syndrome; Skin; Skin Diseases

Topics: Animals; Cells, Cultured; Ceruloplasmin; Collagen; Copper; Cutis Laxa; Ehlers-Danlos Syndrome; Elastin; Hepatolenticular Degeneration; Humans; Liver; Menkes Kinky Hair Syndrome; Mice; Protein-Lysine 6-Oxidase

The elastic fibers present in various connective tissues of the body are responsible for physiologic elasticity of the organs. These fibers consist of 2 distinct components, elastin and the elastic fiber microfibrils. Controlled synthesis and balanced interaction of these 2 components are essential for normal fibrillogenesis. The intracellular biosynthesis of elastin by connective tissue cells, such as smooth muscle cells, involves assembly of the polypeptide chains on the membrane-bound ribosomes, hydroxylation of some prolyl residues to hydroxyproline, and secretion of the polypeptides packaged in Golgi vacuoles. In the extracellular space the elastin molecules assemble into fiber structures which are stabilized by the synthesis of complex covalent cross-links, desmosines. Recently, aberrations in the structure or metabolism of elastin have been detected in a variety of heritable and acquired diseases affecting skin and other connective tissues. These conditions include pseudoxanthoma elasticum, cutis laxa, and elastosis perforans serpiginosa, as well as arteriosclerosis and other degenerative changes of the vascular connective tissues.

Topics: Amino Acids; Arteriosclerosis; Chemical Phenomena; Chemistry; Collagen Diseases; Connective Tissue; Contractile Proteins; Cutis Laxa; Desmosine; Ehlers-Danlos Syndrome; Elastic Tissue; Elastin; Female; Glycoproteins; Humans; Hydroxyproline; Marfan Syndrome; Menkes Kinky Hair Syndrome; Muscle Proteins; Pancreatic Elastase; Peptide Biosynthesis; Protein Precursors; Pseudoxanthoma Elasticum; X Chromosome

The macular mouse is a mutant mouse with the same gene abnormality as that of Menkes' disease, and it exhibits symptoms and abnormalities similar to those of Menkes' disease. In an electron microscopic study, we examined morphological changes in the internal elastic lamina (IEL) of the elastic arteries (EA) and the muscular arteries (MA) in a patient with Menkes' disease and in the macular mouse, an animal model of this disease. The IEL of the EA was significantly thinner in the macular mouse than that in controls, but the IEL of the MA in the macular mouse was significantly thicker than that of the controls. These contrary results for the thickness of the IEL in the MA and the EA in this animal model of Menkes' disease may reflect differences in the anatomical and pathophysiological properties of the two types of vessels.

Topics: Animals; Blood Vessels; Child, Preschool; Disease Models, Animal; Elastic Tissue; Elastin; Female; Humans; Immunohistochemistry; Male; Menkes Kinky Hair Syndrome; Mice; Mice, Mutant Strains; Microscopy, Electron

Ultrastructural studies of the skin and aorta of a patient with Menkes disease, an X-linked recessive disorder of copper metabolism, are described. Dermal thickness was normal, while dermal collagen fibrils exhibited a heterogeneous size range, with a mean diameter smaller than normal. Long-spacing collagen was often observed near fibroblasts, the plasma membranes of which were decorated by aggregates of interwoven filaments. Dermal elastin fibers were scarce and consisted of thin strands of amorphous elastin associated with numerous microfibrils. In the aorta, the amount of collagen was normal, although the fibrils displayed a broader range of diameters than normal, with a slightly smaller mean. Elastin fibers showed considerable disruption, appearing fragmented and wider than normal, and displaying irregular contours. The inclusion of cationic dyes during tissue fixation gave rise to numerous electron-dense precipitates within the elastin fibers, suggesting the presence there of glycosaminoglycans or proteoglycans, among which unsulfated and sulfated chondroitins were demonstrated by immunoelectron microscopy to be prominent. Heparan sulfate, observed to be a constituent of normal elastin fibers, was much reduced in amount. Elastin was also found associated with glycosaminoglycans in the soluble matrix of the aortic wall.

Topics: Aorta; Child; Child, Preschool; Collagen; Elastin; Extracellular Matrix; Glycosaminoglycans; Humans; Infant; Infant, Newborn; Male; Menkes Kinky Hair Syndrome; Microscopy, Immunoelectron; Skin

Topics: Adult; Animals; Arteriosclerosis; Child; Child, Preschool; Copper; Elastin; Female; Fetus; Humans; Infant; Infant, Newborn; Male; Mammary Arteries; Menkes Kinky Hair Syndrome; Muscle, Smooth, Vascular; Myocardial Revascularization; Pregnancy; Saphenous Vein; Swine; Thoracic Arteries

Previous morphologic observations have suggested abnormalities in the elastic fibers in a number of both inherited and acquired diseases. Recent progress made in understanding of the normal biology of elastin has allowed us to examine these diseases by biochemical means. In this review we are discussing the current status of the research on the elastin diseases with particular emphasis on clinical conditions affecting skin, as for example, cutis laxa, pseudoxanthoma elasticum, and the Buschke-Ollendorff syndrome. In addition, we present new data which appears to be the first demonstration of an elastin abnormality in the Marfan syndrome.

Topics: Connective Tissue Diseases; Cutis Laxa; Elastin; Humans; Marfan Syndrome; Menkes Kinky Hair Syndrome; Pseudoxanthoma Elasticum; Skin; Skin Diseases

Lysyl oxidase activity against both collagen and elastin substrates has been examined in the culture medium of skin fibroblasts derived from unrelated patients with Menkes' syndrome and from control subjects. The medium of three Menkes' fibroblast lines showed 3--30% of the activity present in the medium of control fibroblasts, against a purified collagen substrate. Lysyl oxidase activity in the culture medium of two of the Menkes' fibroblast lines was also examined by using a crude aortic-elastin substrate and was similarly decreased in comparison with that in the medium of control fibroblasts. Lysyl oxidase activity in the medium of a fourth fibroblast line, derived from a foetus with Menkes' syndrome, was 42% of that in the medium of control fibroblasts derived from a 1-day-old baby against a collagen substrate, and 26% of that in control fibroblast medium against an elastin substrate. The copper content of the cell layers of the Menkes' fibroblast cultures was elevated in comparison with normal fibroblast cultures, as has previously been reported to be characteristic of such cells. It is suggested that the decrease in lysyl oxidase activity would help to explain the connective tissue defects observed in Menkes' syndrome, and that this reduction, in conjunction with the elevated concentrations of cellular copper, would support the hypothesis that a functional intracellular copper deficiency exists in Menkes' syndrome.

Topics: Adult; Amino Acid Oxidoreductases; Brain Diseases, Metabolic; Cells, Cultured; Collagen; Copper; Culture Media; Elastin; Fibroblasts; Humans; Infant, Newborn; Menkes Kinky Hair Syndrome; Protein-Lysine 6-Oxidase; Skin

The biosynthetic activities of protein and collagen from the patient of kinky hair disease, were reduced to 70 and 50%, respectively, compared with control. In tissue cultures, fast-green FCF staining coarse granules were found in the cytoplasm of skin fibroblasts from the patient. Ultrastructurally, collagen fibrils by iliac cartilage biopsy were irregular in width. Ruthenium red staining granules, presumed to be proteoglycans in the cartilage matrix, were relatively small in size and few in number. Chondrocytes showed poor development of organelles and relatively small glycogen accumulation.

Topics: Brain Diseases, Metabolic; Cartilage; Cells, Cultured; Child, Preschool; Collagen; Cytoplasm; Elastin; Fibroblasts; Humans; Ilium; Infant; Male; Menkes Kinky Hair Syndrome; Microscopy, Electron; Proteoglycans; Skin