Decreased content of the IL1 alpha processing enzyme calpain in murine bone marrow-derived macrophages after treatment with the benzene metabolite hydroquinone.
Benzene is an important industrial chemical known to produce hematotoxicity in mice and humans. Hydroquinone, a major metabolite of benzene, inhibits conversion of the precursor form of IL1 alpha (pre-IL1 alpha) to IL1 alpha in murine bone marrow-derived macrophages in vitro, and a similar effect can be demonstrated in vivo after treatment of mice with benzene. The protease which converts pre-IL1 alpha to IL1 alpha is calpain. We examined decreases in calpain content in bone marrow-derived macrophages as a possible mechanism underlying hydroquinone-induced decreases in pre-IL1 alpha conversion. Hydroquinone, at concentrations which were not overtly cytotoxic, decreased total calpain activity in macrophages by 10-30%. Using immunoblot analysis macrophage calpain II levels were shown to be decreased by approximately 50% after treatment with hydroquinone. Under the same conditions, no changes were observed in calpain I content using immunoblot analysis. These data show that decreased calpain II content represents a potential mechanism of hydroquinone-induced inhibition of pre-IL1 alpha processing, and may contribute to benzene-induced alterations in bone marrow stromal cell function and myelotoxicity.
Miller
A C
AC
Molecular Toxicology and Environmental Health Sciences Program, School of Pharmacy and Cancer Center, University of Colorado Health Sciences Center, Denver 80262.
Schattenberg
D G
DG
Malkinson
A M
AM
Ross
D
D
D000818:Animals; D001854:Bone Marrow Cells; D002154:Calpain / Q000037:antagonists & inhibitors* / Q000187:drug effects; D006873:Hydroquinones / Q000633:toxicity*; D007375:Interleukin-1 / Q000096:biosynthesis*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice
D006873:Hydroquinones; D007375:Interleukin-1; D002154:Calpain; C031927:hydroquinone