EXPRESSION OF A CU,ZN SUPEROXIDE-DISMUTASE TYPICAL OF FAMILIAL AMYOTROPHIC-LATERAL-SCLEROSIS INDUCES MITOCHONDRIAL ALTERATION AND INCREASE OF CYTOSOLIC CA2-SY5Y CELLS( CONCENTRATION IN TRANSFECTED NEUROBLASTOMA SH)

We have set up a model system for familial amyotrophic lateral scleros is (FALS) by transfecting human neuroblastoma cell line SH-SY5Y with p lasmids directing constitutive expression of either wild-type human Cu ,Zn superoxide dismutase (Cu,ZnSOD) or a mutant of this enzyme (G93A) associated with FALS. We have tested mitochondrial function and determ ined cytosolic Ca2+ concentration in control cells (untransfected) and in cells expressing either wild-type Cu,ZnSOD or G93A, We report that G93A induces a significant loss of mitochondrial membrane potential, an increased sensitivity toward valinomycin and a parallel increase in cytosolic Ca2+ concentration, The above phenomena are not related to total Cu,ZnSOD content and activity in the cell. (C) 1997 Federation o f European Biochemical Societies.