Cytoplasmic Cu/Zn superoxide dismutase (SOD1) is an antioxidant enzyme that converts superoxide to hydrogen peroxide in cells. Its spatial distribution matches that of superoxide production, allowing it to protect cells from oxidative stress. SOD1 deficiencies result in embryonic lethality and a wide range of pathologies in mice, but little is known about normal SOD1 protein expression in devel...

The role of Mycoplasma pneumoniae-generated superoxide and hydrogen peroxide in inducing host cell injury was studied in normal and trisomy 21 human cells. As a result of M. pneumoniae infection, catalase activity in infected normal skin fibroblasts and ciliated epithelial cells decreased by 74-77% as compared with uninfected controls. Addition of superoxide dismutase to the infected cultured c...

Amyotrophic lateral sclerosis (ALS) is a fatal degenerative disease of motor neurons. About 10 % of ALS cases are affected in a familial trait, a subset of which is caused by the mutation of Cu, Zn-superoxide dismutase (SOD1) gene (Rosen et al., 1993). Since the identification of the gene for familial ALS, research emphasis for ALS has been placed on uncovering the pathogenic mechanism of motor...

Impairment of endothelium-dependent responses is an early landmark of endothelial dysfunction in blood vessels with aging and/or cardiovascular diseases.1 A critical manifestation of endothelial dysfunction is the reduced bioavailability of NO, a key vascular protective molecule and an independent predictor of cardiovascular events.2 Hence, stimuli decreasing vascular NO bioavailability manifes...

Copper chaperone for superoxide dismutase 1 (SOD1), CCS, is the physiological partner for the complex mechanism of SOD1 maturation. We report an in vitro model for human CCS-dependent SOD1 maturation based on the study of the interactions of human SOD1 (hSOD1) with full-length WT human CCS (hCCS), as well as with hCCS mutants and various truncated constructs comprising one or two of the protein...

Superoxide Dismutase 1 mutants associate with 20-25% of familial Amyotrophic Lateral Sclerosis (ALS) cases, producing toxic aggregates on mitochondria, notably in spinal cord. The Voltage Dependent Anion Channel isoform 1 (VDAC1) in the outer mitochondrial membrane is a docking site for SOD1 G93A mutant in ALS mice and the physiological receptor of Hexokinase I (HK1), which is poorly expressed ...

The neuronal adaptor protein X11alpha participates in the formation of multiprotein complexes and intracellular trafficking. It contains a series of discrete protein-protein interaction domains including two contiguous C-terminal PDZ domains. We used the yeast two-hybrid system to screen for proteins that interact with the PDZ domains of human X11alpha, and we isolated a clone encoding domains ...

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive loss of motor neurons leading to paralysis and death. Mutations of the human Cu/Zn superoxide dismutase (SOD1) are found in some cases of familial ALS (fALS). Recent evidences suggest the accumulation of intracellular calcium is one of the primary mechanisms of motor neuronal degeneration. In th...

Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by loss of neurons in the substantia nigra that project to the striatum and release dopamine. The cause of PD remains uncertain, however, evidence implicates mitochondrial dysfunction and oxidative stress. Although most cases of PD are sporadic, 5-10% of cases are caused by inherited mutations. Loss-of-function mu...