Effect of copper overload on the survival of HepG2 and A-549 human-derived cells.
We investigated the effect of copper (Cu) overload (20-160 µM/24 h) in two cell lines of human hepatic (HepG2) and pulmonary (A-549) origin by determining lipid and protein damage and the response of the antioxidant defence system. A-549 cells were more sensitive to Cu overload than HepG2 cells. A marked increase was observed in both the cell lines in the nitrate plus nitrite concentration, protein carbonyls and thiobarbituric acid reactive substances (TBARS). The TBARS increase was consistent with an increment in saturated fatty acids at the expense of polyunsaturated acids in a Cu concentration-dependent fashion. Antioxidant enzymes were stimulated by Cu overload. Superoxide dismutase activity increased significantly in both the cell lines, with greater increases in HepG2 than in A-549 cells. A marked increase in ceruloplasmin and metallothionein content in both the cell types was also observed. Dose-dependent decreases in α-tocopherol and ferric reducing ability were observed. Total glutathione content was lower in A-549 cells and higher in HepG2. Calpain and caspase-3 were differentially activated in a dose-dependent manner under copper-induced reactive oxygen species production. We conclude that Cu exposure of human lung- and liver-derived cells should be considered a reliable experimental system for detailed study of mechanism/mechanisms by which Cu overload exerts its deleterious effects.
Facultad de Ciencias Médicas, Instituto de Investigaciones Bioquímicas de La Plata, CCT La Plata, CONICET-UNLP, Cátedra de Bioquímica y Biología Molecular, Universidad Nacional de La Plata, La Plata, Argentina.
N
N
Arnal
M J T
MJ
de Alaniz
C A
CA
Marra
D002154:Calpain / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002570:Ceruloplasmin / Q000378:metabolism; D003300:Copper / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D009566:Nitrates; D009573:Nitrites; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D003300:Copper; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D002570:Ceruloplasmin; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D002154:Calpain; D053148:Caspase 3; D005978:Glutathione