ALTERATIONS IN THE NEUTRAL PROTEINASE ACTIVITIES OF CENTRAL AND PERIPHERAL NERVOUS SYSTEMS OF ACRYLAMIDE-TREATED, CARBON DISULFIDE-TREATED,OR 2,5-HEXANEDIONE-TREATED RATS

Proteinases are widespread in neuronal or nonneuronal eukaryotic cells . They are suggested to play an important role in the turnover of prot eins in neuronal perikaryon and axon, and digestion of the transported cytoskeletal proteins in synaptic terminals. We examined the effect o f acrylamide (50 mg/kg, ip), carbon disulfide (700 ppm, 9 h, 7 d a wee k), and 2,5-hexanedione (2,5-HD) (1% in drinking water) treatment of r ats on mCANP (2 mM Ca2+), mu CANP (0.1 mM Ca2+), and CINP (Ca2+-indepe ndent) activity in telencephalon + diencephalon (FB), rhombencephalon + mesencephalon (LB), spinal cord (SC), and sciatic nerve (SN). The pr oteinase activity was determined in the 30,000g supernatant fraction o f tissues using C-14-methylated casein as the substrate. mCANP activit y in FB, LB, and SC was inhibited only by acrylamide. Acrylamide or 2, 5-HD treatment had no effect on mu CANP and CINP activities of SN, whe reas carbon disulfide enhanced mu CANP after 15 d and CINP activity af ter 10 d. It is suggested that alteration in in vitro calpain activity shown by these chemicals may not be directly related to their neuroto xic effect. However, calpain may still be playing a role in this polyn europathy by alteration in activity through inflow of Ca2+, release of Ca2+ from intracellular organelles, or other factors. Modification of cytoskeletal proteins making them more susceptible to proteases and t he role of some other proteinase is also possible.