Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.4.3.13 (lysyl oxidase)
 1,248 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The moose (Alces alces L.) in an acid rain affected region in south-west Sweden has developed a complex disease with numerous clinical signs, most of which are consistent with those of secondary copper (Cu) deficiency and/or molybdenosis in cattle and sheep. The clinical signs of the moose disease reported to date include diarrhoea, anorexia, emaciation, achromotrichia, alopecia, sudden heart failure and osteoporosis. Findings at necropsy included mucosal oedema, atrophied lymphoid tissues of the mucous membranes of the alimentary tract, neuropathy, neuronal degeneration and uni- or bilateral corneal opacity. In a study of clinically healthy animals from the affected region in Sweden over a 12-year period (1982-1994), the hepatic Cu concentration decreased by 50% and the liver and kidney cadmium (Cd) concentration decreased by 25-35%, while the molybdenum (Mo) concentration increased by 20-40%. These changes are probably related to an increase in the pH of the soil and water in the moose environment and a consequent change in the uptake of these elements by the plants consumed by the moose. It is noteworthy that the occurrence of the disease in the mid 1980s coincided with increased liming undertaken to counteract the noxious effects of acid rain in this region. Clinical signs and lesions of the moose disease resemble those reported for Cu deficiency and/or molybdenosis in cattle and sheep. To elucidate the complex, multi-faceted clinical signs of the moose disease, the clinical signs and necropsy findings are discussed in relation to the biochemical functions of certain well-known Cu-dependent enzymes, e.g. depigmentation of hair due to depressed tyrosinase activity, osteoporosis by depressed lysyl oxidase activity, sudden heart failure due to decreased activity of lysyl oxidase, cytochrome c oxidase and Cu/Zn-superoxide dismutase; in addition, mucosal lesions and ulcerations due to loss of activity of diamine oxidase as well as of lysyl oxidase and cytochrome c oxidase. It is concluded from the present findings that the moose disease is most probably a Cu deficiency and/or a molybdenosis-type syndrome.
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PMID:'Mysterious' moose disease in Sweden. Similarities to copper deficiency and/or molybdenosis in cattle and sheep. Biochemical background of clinical signs and organ lesions. 949 61

Elevated homocysteine (Hcys) serum levels represent a risk factor for several chronic pathologies, including cardiovascular disease, atherosclerosis, and chronic renal failure, and affect bone development, quality, and homeostasis. Hcys influences the formation of a stable bone matrix directly through the inhibition of the collagen cross-linking enzyme lysyl oxidase (Lox) and, as we have shown recently, by repressing its mRNA expression. The aim of this study was to investigate the mechanisms involved in this process. Through evaluation of gene arrays, quantitative RT-PCR, immunoblots, and ELISA, we identified a Hcys-dependent stimulation of interleukin 6 (IL-6) and genes involved in IL-6/Janus kinase 2 (JAK2)-dependent signal transduction pathways in pre-osteoblastic MC3T3-E1 cells. Moreover, up-regulation of genes essential for epigenetic DNA methylation (DNA (cytosine-5)-methyltransferases and helicase lymphoid-specific (Hells) was observed. Further investigations demonstrated that Hcys increased via IL-6/JAK2 the expression of Fli1 (Friend leukemia virus integration 1), a transcription factor, which we found essential for IL-6-dependent Dnmt1 stimulation. CpG methylation analysis of CpG-rich Lox proximal promoter revealed an increased CpG methylation status after treatment of the cells with Hcys indicating an epigenetic origin for Hcys-dependent Lox repression. Inhibition of the IL-6/JAK2 pathway or of CpG methylation reversed the repressive effect of Hcys on Lox expression. In conclusion, we demonstrate that Hcys stimulates IL-6 synthesis in osteoblasts, which is known to affect bone metabolism via osteoclasts. Furthermore, IL-6 stimulation results via JAK2, Fli1, and Dnmt1 in down-regulation of Lox expression by epigenetic CpG methylation revealing a new mechanism negatively affecting bone matrix formation.
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PMID:Homocysteine suppresses the expression of the collagen cross-linker lysyl oxidase involving IL-6, Fli1, and epigenetic DNA methylation. 2114 17