| Autor: |
Persoon-Rothert M; Department of Cardiology, University Hospital, Leiden, The Netherlands., Egas-Kenniphaas JM, van der Valk-Kokshoorn EJ, Mauve I, van der Laarse A |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of molecular and cellular cardiology [J Mol Cell Cardiol] 1990 Oct; Vol. 22 (10), pp. 1147-55. |
| DOI: |
10.1016/0022-2828(90)90078-g |
| Abstrakt: |
Oxidative stress induced by cumene hydroperoxide was studied in cultured neonatal rat myocytes. A progressive increase of irreversible cell injury as determined by leakage of the cytoplastic enzyme alpha-hydroxybutyrate dehydrogenase (alpha-HBDH) from the cells was noted at concentrations ranging from 25-100 microM cumene hydroperoxide (incubation time 90 min). Cumene hydroperoxide-induced damage was reduced or prevented by several compounds: the application of Trolox C, a water-soluble vitamin E analogue, and of phospholipase A2 inhibitors chlorpromazine and (to a lesser extent) quinacrine prevented alpha-HBDH release. ICRF-159, a chelator of divalent cations, ascorbic acid, a potent antioxidant, and the cysteine protease inhibitor leupeptin did not reduce the cumene hydroperoxide-induced cytotoxicity. Detoxification of hydroperoxides by the glutathione peroxidase system results in an increased flux through the pentose phosphate shunt and loss of NADPH. Glucose inhibited the cumene hydroperoxide-induced alpha-HBDH release, probably by replenishing NADPH. These results indicate that cumene hydroperoxide, after exhaustion of the glutathione system, induces irreversible injury in cultured myocytes by a mechanism that depends to a large extent on deterioration of cellular membranes caused by lipid peroxidation and phospholipase activation. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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