Effects of lead and manganese on the release of lysosomal enzymes in vitro and in vivo.
In this study we evaluated the effects of two heavy metals, lead and manganese, on the release of some glycohydrolases of lysosomal origin. N-acetyl-beta-D-glucosaminidase and its major isoenzymes, beta-D-glucuronidase and alpha-D-galactosidase. We have studied release of these enzymes in vitro from peripheral mitogen-activated lymphocytes from healthy subjects after addition of Pb or Mn to the medium and their plasma levels in individuals exposed at work to Pb (31 subjects) or to manganese (36 subjects), versus matched controls. We also determined the plasma levels in a general population (417 subjects). The enzymatic activities were assayed fluorimetrically with 4-methylumbelliferyl-glycosides as substrates. Particular attention was given to some technical aspects: enzymatic activity was preserved by addition of ethylene glycol and stable liquid material was employed for calibration purposes. N-acetyl-beta-D-glucosaminidase isoenzymes were separated by a routine chromatofocusing procedure on PBE 94. The addition of both metals to lymphocytes inhibits lysosomal enzyme release. These data were supported by the plasma levels for the exposed subjects, in which enzyme levels were significantly decreased after either type of exposure. In the general population of subjects not professionally exposed, the effect of lead appears to be masked by concomitant effects of alcohol consumption. Undoubtedly, some heavy metals can alter distribution of glycohydrolases of lysosomal origin between the intra- and extracellular environment, probably interfering with membrane mechanisms. Lysosomal enzymes seem to behave as sensitive biomarkers for early subclinical changes that might later lead to clinical disease.
Bairati
C
C
Department of Medical Chemistry and Biochemistry, Medical School, University of Milan, Italy.
Goi
G
G
Bollini
D
D
Roggi
C
C
Luca
M
M
Apostoli
P
P
Lombardo
A
A
D000118:Acetylglucosaminidase / Q000097:blood / Q000187:drug effects; D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D003470:Culture Media / Q000378:metabolism; D005260:Female; D005966:Glucuronidase / Q000097:blood / Q000187:drug effects; D006026:Glycoside Hydrolases / Q000097:blood* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007854:Lead / Q000097:blood / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008247:Lysosomes / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D008345:Manganese / Q000097:blood / Q000494:pharmacology*; D019216:Metals, Heavy / Q000097:blood / Q000494:pharmacology; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology; D016273:Occupational Exposure; D010835:Phytohemagglutinins / Q000494:pharmacology; D000519:alpha-Galactosidase / Q000097:blood / Q000187:drug effects
D003470:Culture Media; D019216:Metals, Heavy; D008934:Mitogens; D010835:Phytohemagglutinins; D007854:Lead; D008345:Manganese; D006026:Glycoside Hydrolases; D000519:alpha-Galactosidase; D005966:Glucuronidase; D000118:Acetylglucosaminidase