ALLYLAMINE AND-AMINOPROPIONITRILE-INDUCED VASCULAR INJURY: ENHANCED EXPRESSION OF HIGH-MOLECULAR-WEIGHT PROTEINS

Abstract

In the present study we describe changes in aorta at the protein level associated with allylamine (AA) and-aminopropionitrile ( APN) induced vascular toxicity in a rat model. This model represents a remarkable synergistic, necrotizing toxic effect of these combined toxins, and our rationale was to examine protein expression in order to shed light on the mechanisms underlying this synergism. Rats were given AA (100 mg kg body weight day) and APN (1 g kg body weight day) by gavage for 10 d; this protocol has been shown to result in smooth-muscle necrosis, but no visible connective tissue changes. Soluble and insoluble fractions from AA APN- or from APN-treated aorta showed enhanced expression of three high-molecular-weight protein bands (ranges between approximately 120 and 95 kD). The time course of induction of proteins showed the appearance of AA APN-induced specific proteins at d 3 of AA APN treatment. Partial purification and characterization suggested that AA APN specific proteins are likely to be collagen proteins (type I). Thus, the data presented in this article help in understanding the vascular toxicity induced by AA APN or by APN, in that we have described an altered phenotypic expression of collagenous proteins indicative of selective medial vascular toxicity.