Nutrition and lysosomal activity. The influence of the vitamin A status on the proteolytic activity of extracts from the livers and kidneys of rats

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Abstract
Young rats were kept for several weeks on a diet deficient in vitamin A. Some were undosed, others were given marginal [25 international units (IU) weekly], adequate (1000 I. U. weekly) or excessive (50, 000 I. U. daily) doses of vitamin A acetate. The undosed rats developed signs of vitamin A deficiency, and the overdosed animals had skeletal fractures indicative of hypervitaminosis A. The rats were decapitated. Their livers, and sometimes their kidneys, were homogenized and processed by centrifugal methods to sediment most of the lysosome fractions. Proteolytic activity was measured, after treatment with a detergent, in the whole homogenate (''total'' activity), in the pellet obtained after 20 min. at 15, OOOg (''bound'' activity) and without treatment with detergent, in the supernatant (''free'' activity). In rats suffering from hypervitaminosis A the free activity and to a smaller extent the total activity were increased. Free activity was also raised in most rats suffering from avitaminosis A, but less than in those suffering from hypervitaminosis. The vitamin A status appeared to have little effect on the proteolytic activity of the kidneys. Results for total and free activities, but not for bound activities, were higher than for corresponding liver preparations. Control experiments were done on starved rats and on rats which were pair-fed with hypervitaminotic animals. Short periods of starvation caused an increase in free activity in young rats, but not in adults. The increases caused by starvation were much less than those caused by hypervitaminosis A. For studies of the distribution of vitamin A more complete separation of the subcellular fractions was carried out on the combined livers from several hypervitaminotic rats. The concentration of vitamin A in the lysosome fraction was less than in the liver as a whole. Our finding that the free proteolytic activity of the liver is increased by toxic oral dosing with vitamin A can be considered an extension of the previous observation that proteolytic enzymes are liberated when lysosomes are treated in vitro with vitamin A.