Evidence for the presence of active cytochrome P450 systems in Schistosoma mansoni and Schistosoma haematobium adult worms.
Extracts of the adult worms of both Schistosoma mansoni and Schistosoma haematobium can metabolise some typical P450 substrates but to differing degrees. S. mansoni worm extracts displayed a approximately 12-fold higher specific activity for an aminopyrine substrate than rat liver microsomes. At 4 mM substrate concentration the demethylation reaction with N-nitrosodimethylamine (NDMA) (5 nmol HCHO/mg protein/min) was only half that of rat liver microsomes, whereas in extracts of S. haematobium, no detectable activity was found towards NDMA. Using ethylmorphine as substrate the demethylation activity of S. mansoni extracts (1.82 nmol HCHO/mg protein/min) was 5.5-fold lower than that of rat liver microsomes. Benzphetamine demethylase activity was also readily detectable in S. mansoni worm extracts at 6.79 nmol HCHO/mg protein/min compared with 10.20 nmol HCHO/mg protein/min in the case of rat liver microsomes. When aniline was used as substrate, surprisingly, no activity was found in worm extracts of either S. mansoni or S. haematobium, whereas rat liver microsomes showed high activity towards this amine. The anti-P450 2E1 and 2B1/2 cross-reacted with both worm homogenates and gave a specific band corresponding to a protein of molecular weight of approximately 50.0 kDa. A study with anti-P450 IVA antibody revealed that while this protein was strongly expressed in S. haematobium worm extracts, no immunoreactivity was observed with extracts of S. mansoni. Immunoblotting analyses with anti-P450 IIIA and P450 1A1 did not detect immunoreactive protein in either S. mansoni or S. haematobium.
Saeed
Hesham M
HM
Institute for Graduate Studies and Research, University of Alexandria, Chatby 21526, Alexandria, Egypt. hesham25166@yahoo.com
Mostafa
Mostafa H
MH
O'Connor
Peter J
PJ
Rafferty
Joseph A
JA
Doenhoff
Michael J
MJ
D000632:Aminopyrine / Q000494:pharmacology; D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D001589:Benzphetamine / Q000494:pharmacology; D006224:Cricetinae; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism*; D004128:Dimethylnitrosamine / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005036:Ethylmorphine / Q000494:pharmacology; D005260:Female; D005557:Formaldehyde / Q000032:analysis / Q000378:metabolism; D015151:Immunoblotting; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010078:Oxazines / Q000494:pharmacology; D051381:Rats; D012548:Schistosoma haematobium / Q000737:chemistry / Q000201:enzymology*; D012550:Schistosoma mansoni / Q000737:chemistry / Q000201:enzymology*; D013379:Substrate Specificity
D000814:Aniline Compounds; D010078:Oxazines; D000632:Aminopyrine; D001589:Benzphetamine; D005557:Formaldehyde; C007649:ethoxyresorufin; C044943:pentoxyresorufin; D003577:Cytochrome P-450 Enzyme System; D009251:NADPH-Ferrihemoprotein Reductase; D004128:Dimethylnitrosamine; D005036:Ethylmorphine; C023650:aniline