SERINE PROTEASES IN RODENT HIPPOCAMPUS

Brain serine proteases are implicated in developmental processes, syna ptic plasticity, and in disorders including Alzheimer's disease. The s pectrum of the major enzymes expressed in brain has not been establish ed previously. We now present a systematic study of the serine proteas es expressed in adult rat and mouse hippocampus. Using a combination o f techniques including polymerase chain reaction amplification and Nor thern blotting we show that tissue-type plasminogen activator (t-PA) i s the major species represented. Unexpectedly, the next most abundant species were RNK-Met-1, a lymphocyte protease not reported previously in brain, and two new family members, BSP1 (brain serine protease 1) a nd BSP2. We report full-length sequences of the two new proteases; hom ologies indicate that these are of tryptic specificity, Although BSP2 is expressed in several brain regions, BSP1 expression is strikingly r estricted to hippocampus, Other enzymes represented, but at lower leve ls, included elastase IV, proteinase 3, complement C2, chymotrypsin B, chymotrypsin-like protein, and Hageman factor. Although thrombin and urokinase-type plasminogen activator were not detected in the primary screen, low level expression was confirmed using specific polymerase c hain reaction primers. In contrast, and despite robust expression of t -PA, the usual t-PA substrate plasminogen was not expressed at detecta ble levels.