Cell permeable ROS scavengers, Tiron and Tempol, rescue PC12 cell death caused by pyrogallol or hypoxia/reoxygenation.
The role of superoxide anion (O(2)*-) in neuronal cell injury induced by reactive oxygen species (ROS) was examined in PC12 cells using pyrogallol (1,2,3-benzenetrior), a donor to release O(2)*-. Pyrogallol induced PC12 cell death at concentrations, which evidently increased intracellular O(2)*-, as assessed by O(2)(*-)-sensitive fluorescent precursor hydroethidine (HEt). Caspase inhibitors, Z-VAD-FMK and Z-Asp-CH(2)-DCB, failed to protect cells from injury caused by elevation of intracellular O(2)*-, although these inhibitors had effects on hypoxia- or hydrogen peroxide (H(2)O(2))-induced PC12 cell death. Two known O(2)*- scavengers, Tiron (4,5-dihydroxy-1,3-benzenedisulfonic acid) and Tempol (4-hydroxy-2,2,6,6-tetramethylpiperydine-1-oxyl) rescued PC12 cells from pyrogallol-induced cell death. Hypoxia/reoxygenation injury of PC12 cells was also blocked by Tiron and Tempol. Further understanding of the underlying mechanism of the protective effects of these radical scavengers reducing intracellular O(2)*- on neuronal cell death may lead to development of new therapeutic treatments for hypoxic/ischemic brain injury.
Yamada
Jun
J
Department of Neurosurgery, Gifu University School of Medicine, Tsukasamachi 40, Gifu 500-8705, Japan.
Yoshimura
Shinichi
S
Yamakawa
Haruki
H
Sawada
Motoshi
M
Nakagawa
Masanori
M
Hara
Shigeru
S
Kaku
Yasuhiko
Y
Iwama
Toru
T
Naganawa
Takashi
T
Banno
Yoshiko
Y
Nakashima
Shigeru
S
Sakai
Noboru
N
D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology*; D000818:Animals; D061945:Caspase Inhibitors; D016923:Cell Death / Q000187:drug effects* / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology*; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D008854:Microscopy, Electron; D010100:Oxygen / Q000378:metabolism; D016716:PC12 Cells; D011748:Pyrogallol / Q000494:pharmacology; D051381:Rats; D015424:Reperfusion; D013113:Spin Labels; D013481:Superoxides / Q000032:analysis / Q000378:metabolism*
D061945:Caspase Inhibitors; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D013113:Spin Labels; D011748:Pyrogallol; D013481:Superoxides; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; D010100:Oxygen; C001803:tempol