Glucose may induce cell death through a free radical-mediated mechanism.
It has been reported that glucose may autooxidize generating free radicals which have been hypothesized to induce important cellular abnormalities. To investigate the cell damage induced by glucose-dependent oxidative stress, the FRTL5 cell strain was incubated in 10 or 20 mM glucose, either alone or in the presence of buthionine-sulfoximine, a transition state inhibitor that blocks glutathione synthesis. We found indeed that buthionine-sulfoximine greatly inhibited glutathione production and increased malondialdehyde (a marker of oxidative cell damage) levels, especially in 20mM glucose. We also found that, when glutathione production was inhibited, 10mM glucose induced apoptosis and 20 mM glucose induced necrosis. These data show that the glucose-dependent cell damage is a function of glutathione production. They also show that such glucose-dependent free radical production may be critical for determining cell damage, even for small variations as the ones we tested (from 10 to 20 mM glucose).
Donnini
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Dipartimento di Patologia e Medicina Sperimentale e Clinica, University of Udine Medical School, Italy.
Zambito
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Perrella
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Ambesi-Impiombato
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D000818:Animals; D019328:Buthionine Sulfoximine; D016923:Cell Death / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D005434:Flow Cytometry; D005609:Free Radicals / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism*; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D011837:Radiation-Protective Agents / Q000494:pharmacology; D051381:Rats; D013961:Thyroid Gland
D005609:Free Radicals; D011837:Radiation-Protective Agents; D008717:Methionine Sulfoximine; D008315:Malondialdehyde; D019328:Buthionine Sulfoximine; D004247:DNA; D005978:Glutathione; D005947:Glucose