Acid hydrolases induction

Fig. 3. Diagrammatic representation of the possible mechanisms underlying acid hydrolase induction. A. Endocytosis and/or phagolysosome formation stimulates ( intermediate) DNA-RNA mechanism. B. DNA-RNA machinery is stimulated through a membrane activated second messenger. C. Direct stimulation of protein-synthesizing system by inducer molecule.

It is reasonable that the process of vesiculation occurs at an equilibrium rate, constant for each cell species and modified by the metabolic demands of the cells. We have suggested (Verity and Brown, 1968b), from maturation studies of cerebral lysosomal enzymes, that for a given rate of vesiculation, the enzyme complement of the primary lysosome is directly proportional to the individual rates of synthesis of the component enzymes. Such a hypothesis would account for the heterogeneity in acid hydrolase reaction to injury, the difference in maturation profiles of individual acid hydrolases, and the dysynchrony of acid hydrolase induction. Also suggested is a direct feedback mechanism whereby a stimulation of vesiculation may in turn induce increased enzyme synthesis, possibly through changes in membrane phospholipid metabolism. 

Proteases contribute to the inflammatory response to injury, forming a final common pathway that leads to BBB breakdown, hemorrhage, and cell death. After traumatic and ischemic injuries, there is a buildup of lactate, which is increased with hyperglycemia. Acidosis leads to release of acid hydrolases, which are destructive enzymes that attack cellular components, including membranes, resulting in cell necrosis. In situations where the pH remains neutral, increases in intracellular calcium and cytokines cause induction of neutral proteases. The main neutral proteases are the extracellular matrix-degrading MMPs, plasminogen activator/plasmin, and caspases. 

The synthesis of enzymes is a continuous process in every living celL Synthesis of acid hydrolases in mammalian cells requires not only the possession of the appropriate gene but also the presence of a specific substrate or a substance closely related to it to act as specific enzyme inducer. The phenomenon is termed enzyme induction. The opposite phenomenon exists and is referred to as enzyme repression. Acid hydrolases in a cell will depend, therefore, upon the presence of the particular gene... 

The induction of specific acid hydrolase synthesis is the result of (1) a... 

Kawashima Y, Uy-Yu N, Kozuka H Sex-related difference in the inductions by perfluorooctanoic acid of peroxisomal fl-oxidation, microsomal 1-acylglycerophos-phocholine acyltransferase and cytosolic long-chain acyl-CoA hydrolase in rat liver. Biochem J 26 595-6Q0, 1989... 

Induction of de novo synthesis of a-amylase by GA in isolated aleurone layers is evident after a lag period of approximately 8 hr following administration of the hormone. In keeping with hormone responses generally, GA must be present continuously if the de novo synthesis of hydrolases is to be sustained. Synthesis of new RNA is essential to the GA-induction of de novo synthesis of hydrolases. Actinomycin D, an inhibitor of RNA synthesis, inhibits the synthesis and release of a-amylase if the inhibitor is presented during the first 7 to 8 hr after treatment. Inhibitors of protein synthesis, such as cycloheximide, also inhibit GA-induction of hydrolases. And, interestingly, abscisic acid, a growth-inhibiting hormone, inhibits GA-induced a-amylase synthesis as well. 

The mechanism of action of abscisic acid (ABA) has been studied to the greatest extent in the barley aleurone system (29), in which ABA counteracts the effect of GA in the induction of hydrolases. This action of ABA has largely been the basis for speculating that ABA may act specifically to inhibit, by some unknown mechanism, DNA-dependent RNA synthesis. Much evidence indicates that ABA acts at the transcriptional level, but it also has been proposed that the inhibition of induction of a-amylase synthesis is caused, at least in part, by an effect on translation because ABA still inhibited the formation of a-amylase at 12 hr when cordycepin (an inhibitor of RNA synthesis) no longer had an effect (30). 

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