Copper overload in human A-549 cells: effects on lipid composition and antioxidant defense system.

ARNAL NATHALIE; TACCONI DE ALANIZ MARíA J.; MARRA CARLOS ALBERTO

Villa Carlos Paz- Córdoba

Congreso; XLIV Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB).; 2008

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB).

We studied in vitro Cu++ overload in human alveolar malignant cells A-540 to test the response of the antioxidant defense system and the possible impact on the fatty acyl composition of total cellular lipids. Exposition to Cu++ (0-180 ìM /24 h) increased thiobarbituric acid-reactive substances, nitrates+nitrites, protein carbonyls, total glutathione, peroxidase and glutathione-transferase activities; and decreased alpha-tocopherol content, total reducing ability (FRAP assay), and glutathione reductase and catalase activities. Superoxide-dismutase was incremented at low Cu++ overload and inhibited at higher concentrations. The rate of cellular growth was strongly depressed in a concentration-dependent manner. Changes were associated to an increased milli- and microcalpaine activation, and with a caspase-3 increment at 40 (but not at 80) ìM Cu++. Fatty acyl composition of total cellular lipids exhibited progressive changes which depend on the Cu++ concentration; mainly a relative increase of saturated fatty acids (especially 16:0 and 18:0) and a substantial loss of PUFAs. Concomitantly, unsaturation index decrease progressively in a [Cu++]-dependent fashion. Modifications induced by Cu may be important in the understanding of the damages associated to involuntary Cu exposure, and also in the etiology of human illnesses such as neurodegenerative disorders.