title: Involvement of intracellular cAMP in epirubicin-induced vascular endothelial cell injury.
abstract: We investigated the involvement of intracellular cAMP in endothelial cell injury induced by epirubicin. Epirubicin-induced decrease in cell viability and increase in caspase-3/7 activity were reversed by a cAMP analog dibutyryl cAMP (DBcAMP) or an activator of adenylate cyclase forskolin concomitant with a phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. Moreover, epirubicin-induced elevation of lipid peroxide levels was attenuated by DBcAMP. Interestingly, the exposure of epirubicin decreased intracellular cAMP levels before the onset of epirubicin-induced production of lipid peroxidation. These results suggest that intracellular cAMP plays an important role in epirubicin-induced endothelial cell injury.
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, Fukuoka 812-8582, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Department of Clinical Pharmacology and Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Mitsuyo
authors.initials: M
authors.lastname: Ueda
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, Fukuoka 812-8582, Japan; Department of Clinical Pharmacology and Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan. Electronic address: n-egashi@pharm.med.kyushu-u.ac.jp.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Egashira
authors.affiliation: Department of Clinical Pharmacology and Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Nina
authors.initials: N
authors.lastname: Zukeyama
authors.affiliation: Department of Clinical Pharmacology and Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kuwahara
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, Fukuoka 812-8582, Japan; Department of Clinical Pharmacology and Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Satohiro
authors.initials: S
authors.lastname: Masuda
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000068600:Albuterol, Ipratropium Drug Combination; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003994:Bucladesine / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D015251:Epirubicin / Q000009:adverse effects* / Q000037:antagonists & inhibitors*; D015227:Lipid Peroxidation / Q000187:drug effects; D008054:Lipid Peroxides / Q000378:metabolism; D013552:Swine
chemical_list: D000068600:Albuterol, Ipratropium Drug Combination; D008054:Lipid Peroxides; D005576:Colforsin; D015251:Epirubicin; D003994:Bucladesine; D000242:Cyclic AMP; D053148:Caspase 3; D053179:Caspase 7; D015056:1-Methyl-3-isobutylxanthine
keywords: Endothelial cell; Epirubicin; cAMP