Cell permeable ROS scavengers, Tiron and Tempol, rescue PC12 cell death caused by pyrogallol or hypoxia/reoxygenation.

Abstract

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.

• Authors: Jun Yamada, Shinichi Yoshimura, Haruki Yamakawa, Motoshi Sawada, Masanori Nakagawa, Shigeru Hara, Yasuhiko Kaku, Toru Iwama, Takashi Naganawa, Yoshiko Banno, Shigeru Nakashima, Noboru Sakai
• Journal: Neuroscience research (Neurosci Res) Vol. 45 Issue 1 Pg. 1-8 (Jan 2003) ISSN: 0168-0102 [Print] Ireland
• PMID: 12507718 (Publication Type: Journal Article)
• Copyright: Copyright 2002 Elsevier Science Ireland Ltd and the Japan Neuroscience Society

Chemical References

• Caspase Inhibitors
• Cyclic N-Oxides
• Free Radical Scavengers
• Spin Labels
• Pyrogallol
• Superoxides
• 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt
• Oxygen
• tempol

Topics

• 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt (pharmacology)
• Animals
• Caspase Inhibitors
• Cell Death (drug effects, physiology)
• Cell Hypoxia (physiology)
• Cyclic N-Oxides (pharmacology)
• Free Radical Scavengers (pharmacology)
• Microscopy, Electron
• Oxygen (metabolism)
• PC12 Cells
• Pyrogallol (pharmacology)
• Rats
• Reperfusion
• Spin Labels
• Superoxides (analysis, metabolism)