Macrophage activation by a vanadyl-aspirin complex is dependent on L-type calcium channel and the generation of nitric oxide.
Bone homeostasis is the result of a tight balance between bone resorption and bone formation where macrophage activation is believed to contribute to bone resorption. We have previously shown that a vanadyl(IV)-aspirin complex (VOAspi) regulates cell proliferation and differentiation of osteoblasts in culture. In this study, we assessed VOAspi and VO effects and their possible mechanism of action on a mouse macrophage cell line RAW 264.7. Both vanadium compounds inhibited cell proliferation in a dose-dependent manner. Nifedipine completely reversed the VOAspi-induced macrophage cytotoxicity, while it could not block the effect of VO. VOAspi also stimulated nitric oxide (NO) production, the oxidation of dihydrorhodamine 123 (DHR-123) and enhanced the expression of both constitutive and inducible isoforms of nitric oxide syntases (NOS). All these effects were abolished by nifedipine. Altogether our finding give evidence that VOAspi-induced macrophage cytotoxicity is dependent on L-type calcium channel and the generation of NO though the induction of eNOS and iNOS. Contrary, the parent compound VO exerted a cytotoxic effect by mechanisms independent of a calcium entry and the NO/NOS activation.
Molinuevo
María Silvina
MS
Cátedra de Bioquímica Patológica, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Departamento de Ciencias Biologicas, 47 y 115, 1900 La Plata, Buenos Aires, Argentina.
Etcheverry
Susana Beatriz
SB
Cortizo
Ana María
AM
D000818:Animals; D001241:Aspirin / Q000031:analogs & derivatives* / Q000633:toxicity*; D015153:Blotting, Western; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D017968:Vanadium Compounds / Q000633:toxicity*
D020746:Calcium Channels, L-Type; D017382:Reactive Oxygen Species; D017968:Vanadium Compounds; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D001241:Aspirin