title: U937 cell apoptosis induced by arsenite is prevented by low concentrations of mitochondrial ascorbic acid with hardly any effect mediated by the cytosolic fraction of the vitamin.
abstract: Arsenite directly triggers cytochrome c and Smac/DIABLO release in mitochondria isolated from U937 cells. These effects were not observed in mitochondria pre-exposed for 15 min to 10 µM L-ascorbic acid (AA). In other experiments, intact cells treated for 24-72 h with arsenite were found to die by apoptosis through a mechanism involving mitochondrial permeability transition. Pre-exposure (15 min) to low micromolar concentrations of AA and dehydroascorbic acid (DHA), resulting in identical cytosolic levels of the vitamin, had a diverse impact on cell survival, as cytoprotection was only observed after treatment with AA. Also the mitochondrial accumulation of the vitamin was restricted to AA exposure. An additional indication linking cytoprotection to the mitochondrial fraction of the vitamin was obtained in experiments measuring susceptibility to arsenite in parallel with loss of mitochondrial and cytosolic AA at different times after vitamin exposure. Finally, we took advantage of our recent findings that DHA potently inhibits AA transport to demonstrate that DHA abolishes all the protective effects of AA, under the same conditions in which the mitochondrial accumulation of the vitamin is prevented without affecting the overall cellular accumulation of the vitamin.
authors: Dipartimento di Scienze Biomolecolari, Università degli Studi di Urbino "Carlo Bo", Urbino, Italy.
authors: Andrea
authors: A
authors: Guidarelli
authors: Mara
authors: M
authors: Fiorani
authors: Catia
authors: C
authors: Azzolini
authors: Liana
authors: L
authors: Cerioni
authors: Maddalena
authors: M
authors: Scotti
authors: Orazio
authors: O
authors: Cantoni
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D051017:Apoptosis Regulatory Proteins; D018053:Arsenites / Q000037:antagonists & inhibitors* / Q000633:toxicity; D001205:Ascorbic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001692:Biological Transport; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D019610:Cytoprotection; D003683:Dehydroascorbic Acid / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D018053:Arsenites; C412403:DIABLO protein, human; D047908:Intracellular Signaling Peptides and Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D024101:Mitochondrial Proteins; D045304:Cytochromes c; C015001:arsenite; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid
keywords: apoptosis; arsenite; cell death; mitochondria; vitamin C