Co-distribution of protease nexin-1 and protease nexin-2 in brains of non-human primates

Abstract

The protease nexins are protease inhibitors which regulate key blood coagulation proteases and which appear to be involved in certain physiological and pathological processes in the brain. Protease nexin-1 (PN-1), a potent inhibitor of thrombin, can regulate processes on cultured neurons and asrocytes. Protease nexin-2 (PN-2), a potent inhibitor of coagulation factor XIa, is identical to the secreted form of the Alzheimer's amyloid β-protein precursor. In the present studies, PN-1 and PN-2 were analyzed in different tissues of monkey using monoclonal antibodies for either quantitative immunoblotting or specific [ 125I]protease-binding assays. PN-1 was detected only in brain. PN-2 was most abundant in brain, followed by testis and to a lesser extent kidney. Other tissues examined including spinal cord, heart, pancreas, spleen, liver, lung and muscle were essentially devoid of both PN-1 and PN-2. Within the brain, the levels of PN-1 and PN-2 were highest in the parietal cortex and lowest in the cerebellum and brainstem. The thalamus and striatum contained intermediate amounts of both proteins. Aged Cebus monkey cerebral cortical tissue contained slightly lower levels of PN-1 than did the middle-aged or young monkey tissue. The co-distribution of PN-1 and PN-2 in brain, their relative abundance in brain cortex, and previous studies on their functions suggest that in the brain they may participate in the regulation of blood coagulation and cell growth and differentiation.