Bestatin as an Experimental Tool in Mammals
O. A. Scornik and V. Botbol
Affiliation: Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755-3844, USA.
Bestatin, an antibiotic of microbial origin, is a potent inhibitor of some, but not all aminopeptidases. It can be administered, with low toxicity, to cultured cells, intact animals and humans. It has become a useful tool in elucidating the physiological role of some mammalian exopeptidases in the regulation of the immune system, in the growth of tumors and their invasion of surrounding tissues, and in the degradation of cellular proteins. Bestatin-sensitive enzymes play important roles in the digestion and absorption of peptides in the brush border of the intestine and the kidney, in the reproductive system, and in the metabolism of opioid peptides and leukotrienes. Aminopeptidase N emerges as the major target for the effects of bestatin on the immune system and some of its effects on tumor growth and the endometrium. It is also the major bestatin-sensitive enzyme involved in the degradation of oligopeptides on the surface of intestine and kidney brush borders, and the inactivation of enkephalins in the brain. Bestatin-sensitive cytosolic exopeptidases are important in the degradation to amino acids of di- and tripeptides generated in most cells by cellular protein degradation, as well as those absorbed through the brush border of intestine and kidney. Inhibition of one of these exopeptidases, cytosol alanine aminopeptidase, results in apoptosis. Bestatin-sensitive cystinyl aminopeptidase is abundant in placenta. Two bestatin-sensitive enzymes, aminopeptidase B and nardilysin, are particularly abundant in late spermatids. Finally bestatin-sensitive LTA4 hydrolase generates the potent chemotactic agent, LTB4.
Keywords: Bestati, aminopeptidases, oligopeptides, enkephalins, bestatin sensitive LTA4 hydrolase, chemotactic agent LTB4, IMMUNE SYSTEM, ANTITUMOR EFFECTS OF BESTATIN, PROTEINDEGRADATION, LEUKOTRIENE METABOLISM
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