Alterations in the neutral proteinase activities of central and peripheral nervous systems of acrylamide-, carbon disulfide-, 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 proteins in neuronal perikaryon and axon, and digestion of the transported cytoskeletal proteins in synaptic terminals. We examined the effect of acrylamide (50 mg/kg, ip), carbon disulfide (700 ppm, 9 h, 7 d a week), and 2,5-hexanedione (2,5-HD) (1% in drinking water) treatment of rats on mCANP (2 mM Ca2+), microCANP (0.1 mM Ca2+), and CINP (Ca(2+)-independent) activity in telencephalon + diencephalon (FB), rhombencephalon + mesencephalon (LB), spinal cord (SC), and sciatic nerve (SN). The proteinase activity was determined in the 30,000g supernatant fraction of tissues using 14C-methylated casein as the substrate. mCANP activity in FB, LB, and SC was inhibited only by acrylamide. Acrylamide or 2,5-HD treatment had no effect on microCANP and CINP activities of SN, whereas carbon disulfide enhanced microCANP after 15 d and CINP activity after 10 d. It is suggested that alteration in in vitro calpain activity shown by these chemicals may not be directly related to their neurotoxic effect. However, calpain may still be playing a role in this polyneuropathy 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 the role of some other proteinase is also possible.
Duke University Medical Center, Department of Pharmacology, Durham, NC, USA.
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Gupta
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Abou-Donia
D020106:Acrylamide; D000178:Acrylamides / Q000633:toxicity*; D000818:Animals; D001259:Ataxia; D001921:Brain / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D002118:Calcium / Q000494:pharmacology; D002246:Carbon Disulfide / Q000633:toxicity*; D003432:Cross-Linking Reagents / Q000633:toxicity; D010450:Endopeptidases / Q000378:metabolism*; D006588:Hexanones / Q000633:toxicity*; D007700:Kinetics; D008297:Male; D009498:Neurotoxins / Q000633:toxicity*; D009928:Organ Specificity; D011480:Protease Inhibitors / Q000633:toxicity; D051381:Rats; D012584:Sciatic Nerve / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D013997:Time Factors
D000178:Acrylamides; D003432:Cross-Linking Reagents; D006588:Hexanones; D009498:Neurotoxins; D011480:Protease Inhibitors; D020106:Acrylamide; C011269:2,5-hexanedione; D010450:Endopeptidases; D002246:Carbon Disulfide; D002118:Calcium