Prevention of reactive oxygen-induced endothelial cell injury by blocking its process.
Endothelial cell (EC) injury induced by reactive oxygen species (ROS) was investigated and effects of Ca(2+) channel blockers, agents which elevate intracellular cAMP levels ([cAMP](i)), and protein kinase inhibitors on H(2)O(2)-induced EC injury were analyzed using human umbilical vein EC cultures. Exposure to H(2)O(2) increased intracellular Ca(2+) levels and decreased [cAMP](i). Ca(2+) channel blockers, [cAMP](i)-elevating agents, and protein kinase inhibitors significantly inhibited H(2)O(2)-induced EC injury. Data suggest that H(2)O(2)-induced EC injury is mediated by extracellular Ca(2+) influx, intracellular cAMP efflux, and intracellular signaling, each of which is blocked by Ca(2+) channel blockers, [cAMP](i)-elevating agents, or protein kinase inhibitors. It is suggested that ischemia/reperfusion injury induced by ROS may be prevented by Ca(2+) channel blockers, [cAMP](i)-elevating agents, and protein kinase inhibitors.
Shimura
H
H
Department of Surgery, Showa University Fujigaoka Hospital, Yokohama, Japan.
Yamaguchi
M
M
Kuzume
M
M
Matsumiya
A
A
Matsumoto
T
T
Sakai
H
H
Hatakeyama
T
T
Nakano
H
H
Kumada
K
K
Midorikawa
T
T
Yoshizawa
Y
Y
Sanada
Y
Y
Ohata
H
H
Sakagami
H
H
Takeda
M
M
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D016227:Benzoquinones; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D053938:DNA Fragmentation; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism; D047029:Lactams, Macrocyclic; D009994:Osmolar Concentration; D016877:Oxidants / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011809:Quinones / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000502:physiology*; D017828:Rifabutin / Q000031:analogs & derivatives
D016227:Benzoquinones; D002121:Calcium Channel Blockers; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D047029:Lactams, Macrocyclic; D016877:Oxidants; D047428:Protein Kinase Inhibitors; D011809:Quinones; D017382:Reactive Oxygen Species; D017828:Rifabutin; D003994:Bucladesine; C020754:herbimycin; D006861:Hydrogen Peroxide; D000242:Cyclic AMP; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine