Glucose, glutathione, and cellular response to spermine oxidation products.
Bovine serum amineoxidase (BSAO) oxidatively deaminates polyamines, which contain primary amine groups with formation of several toxic products, H2O2, and aldehyde(s). We evaluated the role of glucose metabolism via the pentose phosphate cycle and the level of intracellular glutathione on cytotoxicity induced by each of the toxic products in Chinese hamster ovary (CHO) cells. Glucose protected cells against cytotoxicity in the presence of BSAO at low spermine concentrations ( < 50 microM), where H2O2 was the only toxic species present. When catalase was present, cytotoxicity is attributed to spermine-derived aldehyde(s). Glucose did not protect cells against cytotoxicity induced by spermine-derived aldehyde(s), nor by the aldehyde acrolein. Hydrogen peroxide produced by spermine and BSAO stimulated pentose cycle activity, whereas the aldehyde(s) did not. Depletion of intracellular glutathione with L-buthionine sulfoximine (1 mM, 24 h) sensitized cells to the cytotoxic effects of both H2O2 and the aldehyde(s) produced by spermine and BSAO. The pentose cycle and the glutathione redox cycle have an important role in protection against H2O2 generated from spermine oxidation. Glutathione appears to have a role in protecting cells against cytotoxicity attributed to spermine-derived aldehyde(s), most likely by conjugation in a reaction catalyzed by glutathione S-transferase, whereas metabolism of glucose via the pentose cycle did not. The metabolism of both glucose and glutathione, affect the cellular response to H2O2 and aldehyde(s) derived from spermine, although different pathways are involved.
Agostinelli
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Department of Biochemical Sciences (A, Rossi-Fanelli), University of Rome La Sapienza, Italy.
Przybytkowski
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Averill-Bates
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DA
D000171:Acrolein / Q000494:pharmacology; D000447:Aldehydes / Q000378:metabolism; D006631:Amine Oxidase (Copper-Containing); D000818:Animals; D019328:Buthionine Sulfoximine; D016466:CHO Cells / Q000187:drug effects; D002374:Catalase / Q000494:pharmacology; D002417:Cattle; D002470:Cell Survival; D006224:Cricetinae; D005947:Glucose / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D010084:Oxidation-Reduction; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000378:metabolism* / Q000633:toxicity; D010427:Pentose Phosphate Pathway / Q000502:physiology; D013096:Spermine / Q000378:metabolism* / Q000633:toxicity
D000447:Aldehydes; D008717:Methionine Sulfoximine; D013096:Spermine; D019328:Buthionine Sulfoximine; D000171:Acrolein; D006861:Hydrogen Peroxide; D002374:Catalase; D006631:Amine Oxidase (Copper-Containing); D000587:Oxidoreductases Acting on CH-NH Group Donors; D005978:Glutathione; D005947:Glucose