MODULATION OF LYSYL OXIDASE BY DIETARY COPPER IN RATS

Lysyl oxidase levels were estimated in rat tissues using an enzyme-lin ked immunosorption assay (ELISA) and a functional assay standardized a gainst known amounts of purified lysyl oxidase. High concentrations of lysyl oxidase (greater than or equal to 150 mu g/g of tissue or packe d cells) were detected in connective tissues, such as tendon and skin. Values for aorta, kidney, lung and liver ranged from 30 to 150 mu g/g of tissue; values for skeletal muscle and diaphragm were <30 mu g/g t issue. Purified rat skin lysyl oxidase catalyzed the release of 50-100 Bq of tritium per mu g enzyme in assays that used H-3-elastin-rich su bstrates. In dense connective tissues, good agreement was obtained for the values from ELISA and those derived from measurements of function al activity in aorta, lung, skin and tendon (r(2) > 0.9). When egg whi te-based experimental diets containing 2 or 10 mu g/g added copper wer e fed to weanling rats, values for skin lysyl oxidase functional activ ity in the group fed 2 mu g/g added copper were one-third to one-half the values for skin lysyl oxidase functional activity in rats fed 10 m u g/g copper. This reduction in lysyl oxidase activity, however, had m inimal effect on indices of collagen maturation in rat skin, e.g., col lagen solubility in neutral salt and dilute acid or the levels of acid stable cross-links. Moreover, copper deficiency did not influence the steady-state levels of lysyl oxidase specific mRNA in rat skin or the apparent amounts of lysyl oxidase in rat skin as determined by ELISA. These observations underscore that the concentration of lysyl oxidase is relatively high in dense corrective tissues, and although decreasi ng dietary copper influences functional activity, there is little appa rent effect on the production of lysyl oxidase protein.