1. Doxorubicin-induced expression of LOX-1 in H9c2 cardiac muscle cells and its role in apoptosis.
- Author
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Spallarossa P, Fabbi P, Manca V, Garibaldi S, Ghigliotti G, Barisione C, Altieri P, Patrone F, Brunelli C, and Barsotti A
- Subjects
- Acetylcysteine pharmacology, Animals, Atenolol pharmacology, Carbazoles pharmacology, Carvedilol, Cell Line, Flow Cytometry, Free Radicals metabolism, Hydrogen Peroxide metabolism, Hydrogen Peroxide pharmacology, Myocytes, Cardiac cytology, Propanolamines pharmacology, RNA, Messenger genetics, RNA, Messenger metabolism, Rats, Razoxane pharmacology, Receptors, LDL genetics, Receptors, Oxidized LDL, Scavenger Receptors, Class E, Up-Regulation drug effects, Apoptosis drug effects, Doxorubicin pharmacology, Myocytes, Cardiac drug effects, Myocytes, Cardiac metabolism, Receptors, LDL metabolism
- Abstract
Up-regulation of LOX-1 is implicated in apoptosis in both vascular smooth muscle cells and in endothelial cells. We examined the effects of doxorubicin on LOX-1 expression in H9c2 cardiomyocytes and the role played by LOX-1 up-regulation in doxorubicin-induced apoptosis. Reactive oxygen species (ROS) formation was assessed by DCF flow cytometry. LOX-1 mRNA and protein expression was assessed by RT-PCR and Western blotting. Apoptosis was evaluated by flow cytometry with annexin/PI double staining. Doxorubicin-induced LOX-1 expression in a concentration- and time-dependent fashion. The doxorubicin-induced ROS formation and the LOX-1 expression were significantly attenuated by pre-treatment with antioxidants. By exposing cells that had been pre-treated with doxorubicin to oxidized-LDL, a LOX-1 agonist, in the presence or in the absence of k-carrageenan, a LOX-1 receptor antagonist, we documented that doxorubicin-induced LOX-1 expression plays a role in inducing apoptosis. These findings suggest that LOX-1 up-regulation is redox-sensitive and may contribute to doxorubicin-induced cardiotoxicity.
- Published
- 2005
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