Oxidative stress caused by glycation of Cu,Zn-superoxide dismutase and its effects on intracellular components.
It is now evident that the redox state of the cell is a pivotal determinant of the fate of cells. Extensive production of reactive oxygen species (ROI) causes necrotic cell death. Even transient or localized production of ROI may mediate a signal for apoptotic cell death, whereas small amounts of ROI function as an intracellular messenger of some growth stimulants. Accumulating evidence supports the concept that decreases in Cu,Zn-superoxide dismutase (SOD) activity causes apoptotic cell death in neuronal cells. Our data using mutant Cu,Zn-SOD related to familial amyotrophic lateral sclerosis (FALS) suggest that glycation itself and ROI produced from the glycated proteins are involved in many diseases, including diabetic complications. Glycation of important cellular components, including lipid, DNA and proteins, induces dysfunction of these components. Mutant proteins in patients with various hereditary diseases would be destabilized by the glycation reaction, as shown in the case of mutant Cu,Zn-SODs, thereby hyperglycaemic conditions would trigger the onset of some hereditary diseases such as FALS and Alzheimer's disease. Glycation, particularly of antioxidative enzymes, would enhance production of ROI, resulting in oxidative damage to the cells.
Fujii
J
J
Department of Biochemistry, Osaka University Medical School, Japan.
Myint
T
T
Okado
A
A
Kaneto
H
H
Taniguchi
N
N
D000690:Amyotrophic Lateral Sclerosis / Q000209:etiology; D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D001665:Binding Sites; D053938:DNA Fragmentation; D006031:Glycosylation; D006801:Humans; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed; D018384:Oxidative Stress / Q000502:physiology*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D010446:Peptide Fragments; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D013482:Superoxide Dismutase