RRC ID 39392
Author Oda T, Iwaoka J, Komatsu N, Muramatsu T.
Title Involvement of N-acetylcysteine-sensitive pathways in ricin-induced apoptotic cell death in U937 cells.
Journal Biosci. Biotechnol. Biochem.
Abstract We have found that the antioxidant N-acetylcysteine (NAC) strongly inhibited ricin-induced apoptotic cell death in U937 cells (human myeloid leukemia), as judged by cytotoxicity, nuclear morphological change, and DNA fragmentation. Consistent with these observations, a significant depletion of cellular glutathione was observed in ricin-treated cells, and NAC prevented the decrease in cellular glutathione. On the other hand, among the caspase inhibitors tested, Z-Asp-CH2-DCB, which inhibited ricin cytotoxicity, also suppressed ricin-mediated glutathione depletion, while NAC did not affect the generation of caspase-3 like activity in ricin-treated cells. These results suggest that glutathione loss takes place downstream from caspase activation during the ricin-induced apoptotic process. Treatment with a specific inhibitor of glutathione biosynthesis, buthionine sulfoximine (BSO) failed to induce apoptosis, and had no effect on the overall extent of ricin-induced apoptosis, even though the glutathione level was decreased to less than 5% of the control level. However, NAC still protected against ricin-induced apoptosis in the BSO-treated cells. We conclude that glutathione loss is one of several apoptotic changes caused by ricin, but is not a sufficient factor for the progress of apoptosis. NAC may prevent ricin-induced apoptosis through maintaining an intracellular reducing condition by acting as a thiol supplier.
Volume 63(2)
Pages 341-8
Published 1999-2
DOI 10.1271/bbb.63.341
PMID 10192917
MeSH Acetylcysteine / metabolism Acetylcysteine / pharmacology* Antioxidants / metabolism Antioxidants / pharmacology* Apoptosis / drug effects* Apoptosis / physiology Buthionine Sulfoximine / pharmacology Caspase 3 Caspase Inhibitors Cell Survival / drug effects Cell Survival / physiology DNA Fragmentation / drug effects DNA Fragmentation / physiology Dose-Response Relationship, Drug Electrophoresis, Agar Gel Enzyme Inhibitors / pharmacology Free Radical Scavengers / metabolism Free Radical Scavengers / pharmacology* Glutathione / pharmacology Glutathione / physiology Humans Microscopy, Fluorescence Oxidative Stress / drug effects Oxidative Stress / physiology Protein Synthesis Inhibitors / pharmacology Ricin / metabolism* U937 Cells
IF 1.297
Times Cited 35
Human and Animal Cells