* The prostaglandin agonist beraprost aggravates doxorubicin-mediated apoptosis by increasing iNOS expression in cardiomyocytes.
- Doxorubicin (DOX) is widely used as an anti-cancer agent although it causes irreversible cardiomyopathy by increasing oxidative stress and deregulating nitric oxide production. Beraprost (BPS), a stable prostacyclin (PGI2) analog, is a potent vasodilator that has beneficial effects on myocardial ischemia. The objectives of the present study were to delineate the uncertain effects of prostcyclin therapy on DOX induced cardiomyopathy and to explore the mechanisms underlying PGI2 and DOX interaction. For this reason, we stimulated endogenous PGI2 production using bicistronic COX-1/PGIS gene transfer and BPS supplementation, and investigated the effects on DOX-induced cardiomyopathy. Caspase-dependent protein content, lactate dehydrogenase (LDH), DNA fragmentation, and TUNEL positive cells were elevated in DOX-treated cardiomyocytes. These indicators were further elevated by adenovirus-COX- 1/PGIS transfection or BPS supplementation. In addition, PGI2 overexpression further increased iNOS expression and superoxide accumulation in cardiomyocytes compared with DOX alone, which may be the reason for aggravated cytotoxicity. Moreover, BPS can induce cAMP response elements (CRE) binding to the iNOS promoter and phospho- cAMP response element binding protein (CREB) expression in a cyclic AMP-dependent manner. Our in vivo studies show that MnTBAP and aminoguanidine treatment of DOX and BPS co-administered in mice can attenuate caspase-3 and PARP-1 protein expression, and improve mouse survival, as observed in the iNOS gene-deleted mice. In conclusion, we demonstrated that BPS or adv-COX-1/PGIS increases PGI2 levels through iNOS expression and peroxynitrite production, via CREB protein phosphorylation; thereby aggravating DOX-mediated cardiotoxicity.
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Overview of noun effects
The noun effects has 1 sense (no senses from tagged texts)
1. effects, personal effects -- (property of a personal character that is portable but not used in
business; "she left some of her personal effects in the house"; "I watched over their effects until
they returned")
Overview of noun effect
The noun effect has 6 senses (first 5 from tagged texts)
1. (101) consequence, effect, outcome, result, event, issue, upshot -- (a phenomenon that follows
and is caused by some previous phenomenon; "the magnetic effect was greater when the rod was
lengthwise"; "his decision had depressing consequences for business"; "he acted very wise after the
event")
2. (11) impression, effect -- (an outward appearance; "he made a good impression"; "I wanted to
create an impression of success"; "she retained that bold effect in her reproductions of the
original painting")
3. (9) effect -- (an impression (especially one that is artificial or contrived); "he just did it
for effect")
4. (2) effect, essence, burden, core, gist -- (the central meaning or theme of a speech or literary
work)
5. (1) effect, force -- ((of a law) having legal validity; "the law is still in effect")
6. effect -- (a symptom caused by an illness or a drug; "the effects of sleep loss"; "the effect of
the anesthetic")
Overview of verb effect
The verb effect has 2 senses (first 2 from tagged texts)
1. (17) effect, effectuate, set up -- (produce; "The scientists set up a shock wave")
2. (3) effect -- (act so as to bring into existence; "effect a change")
--- WordNet end ---