Involvement of hydrogen peroxide in the differentiation and apoptosis of preosteoclastic cells exposed to arsenite
Long-term exposure to sodium arsenite (AsO2) promotes the development of various cancers. Paradoxically, arsenic also induces pro-myelomonocytic leukemia cell differentiation, and at higher concentrations, apoptosis. The present study investigated the effects of AsO2 on preosteoclasts. When treated with 2.5-5 Î¼M AsO2, RAW264.7 cells underwent osteoclast differentiation as evidenced by an increase in the number of multinucleate cells expressing tartrate resistant acid phosphatase (TRAP). The appearance of these phenotypic markers was preceded by a low level increase in extracellular production of H2O2 and was prevented by the addition of catalase (4.5 Î¼g/ml), an enzyme that removes H2O2. Only at high concentrations (10-25 Î¼M) of AsO2 was a significant loss of cell viability and a high level increase in H2O2 production (1.5 Î¼M) observed. Apoptosis was blocked by pretreatment with diphenylene iodonium chloride (2 Î¼M), a NAD(P)H-flavoprotein inhibitor, suggesting the involvement of NADPH-oxidase. The data show that AsO2, dose-dependently, stimulates increasing amounts of H2O2 production. Moreover, at concentrations found in tissues of individuals exposed to geochemical AsO2, osteoclasts underwent an H2O2-dependent differentiation. Therefore, chronic exposure to low-level amounts of AsO2 could result in increased bone resorption and contribute to bone related pathologies. Â© 2006 Elsevier Inc. All rights reserved.
Szymczyk, K. H.; Kerr, B. A.; Freeman, T. A.; Adams, Christopher S.; and Steinbeck, M. J., "Involvement of hydrogen peroxide in the differentiation and apoptosis of preosteoclastic cells exposed to arsenite" (2006). PCOM Scholarly Papers. 1589.