Copper-induced activation of aortic lysyl oxidase in vivo.

Raising day-old chicks on diets lacking copper severely depressed the activity of lysyl oxidase, a copper metalloenzyme in connective tissue. Administration of CuSO4 either through the diet or through intraperitoneal injections restored the lysyl oxidase activity in aortic tissue. Two hours after the chicks received CuSO4 (1 mg/kg) the activity of lysyl oxidase rose rapidly to attain, within 4-6 hr, a new steady-state level which was five to 20 times higher than the basal (saline-injected) activity. Twenty hours after copper administration, activity was still higher, in some experiments double that achieved at 6 hr. Very low amounts of cycloheximide injected intraperitoneally 45 min before and 3 hr after copper suppressed the activation response by two-thirds. Cycloheximide given 2 or 4 hr after the copper was only one-half as effective. Actinomycin D caused only a 10-15% inhibition of the copper-induced activation. The data suggest that copper is a key regulator of lysyl oxidase activity in aorta and may in fact be a major determinant of the steady-state levels of the enzyme in that tissue.