Doxorubicin-induced expression of LOX-1 in H9c2 cardiac muscle cells and its role in apoptosis.
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.
Spallarossa
Paolo
P
Research Center of Cardiovascular Biology, Department of Cardiology, University of Genova, Italy.
Fabbi
Patrizia
P
Manca
Valeria
V
Garibaldi
Silvano
S
Ghigliotti
Giorgio
G
Barisione
Chiara
C
Altieri
Paola
P
Patrone
Franco
F
Brunelli
Claudio
C
Barsotti
Antonio
A
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001262:Atenolol / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D000077261:Carvedilol; D002460:Cell Line; D004317:Doxorubicin / Q000494:pharmacology*; D005434:Flow Cytometry; D005609:Free Radicals / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D011412:Propanolamines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011929:Razoxane / Q000494:pharmacology; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; D015854:Up-Regulation / Q000187:drug effects
D002227:Carbazoles; D005609:Free Radicals; C495136:OLR1 protein, rat; D011412:Propanolamines; D012333:RNA, Messenger; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; D000077261:Carvedilol; D001262:Atenolol; D011929:Razoxane; D004317:Doxorubicin; D006861:Hydrogen Peroxide; D000111:Acetylcysteine