التفاصيل البيبلوغرافية
| العنوان: |
Early oxidative damage induced by doxorubicin: Source of production, protection by GKT137831 and effect on Ca2+ transporters in HL-1 cardiomyocytes. |
| المؤلفون: |
Asensio-López, Mari C.1, Soler, Fernando2, Sánchez-Más, Jesús1, Pascual-Figal, Domingo1,3, Fernández-Belda, Francisco2 fbelda@um.es, Lax, Antonio1 |
| المصدر: |
Archives of Biochemistry & Biophysics. Mar2016, Vol. 594, p26-36. 11p. |
| مصطلحات موضوعية: |
*DOXORUBICIN, *OXIDATIVE stress, *CALCIUM channels, *HEART cells, *RYANODINE receptors, *ION exchange (Chemistry) |
| مستخلص: |
In atrial-derived HL-1 cells, ryanodine receptor and Na + /Ca 2+ -exchanger were altered early by 5 μM doxorubicin. The observed effects were an increase of cytosolic Ca 2+ at rest, ensuing ryanodine receptor phosphorylation, and the slowing of Ca 2+ transient decay after caffeine addition. Doxorubicin triggered a linear rise of reactive oxygen species (ROS) with no early effect on mitochondrial inner membrane potential. Doxorubicin and ROS were both detected in mitochondria by colocalization with fluorescence probes and doxorubicin-induced ROS was totally blocked by mitoTEMPO. The NADPH oxidase activity in the mitochondrial fraction was sensitive to inhibition by GKT137831, and doxorubicin-induced ROS decreased gradually as the GKT137831 concentration added in preincubation was increased. When doxorubicin-induced ROS was prevented by GKT137831, the kinetic response revealed a permanent degree of protection that was consistent with mitochondrial NADPH oxidase inhibition. In contrast, the ROS induction by doxorubicin after melatonin preincubation was totally eliminated at first but the effect was completely reversed with time. Limiting the source of ROS production is a better alternative for dealing with oxidative damage than using ROS scavengers. The short-term effect of doxorubicin on Ca 2+ transporters involved in myocardiac contractility was dependent on oxidative damage, and so the impairment was subsequent to ROS production. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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