TY - JOUR
T1 - Synergism between tumor necrosis factor-α and H2O 2 enhances cell damage in rat PC12 cells
AU - Trembovler, Victoria
AU - Abu-Raya, Saleh
AU - Shohami, Esther
PY - 2003/12/19
Y1 - 2003/12/19
N2 - Tumor necrosis factor-α (TNFα) is harmful in the early phase and beneficial in the long-term phase after brain injury. Reactive oxygen species (ROS) are among the most toxic mediators activated by injury. We speculate that part of the TNFα toxicity is mediated by its synergism with ROS. Thus, toxicity of TNFα and ROS, alone or together, were studied in PC12 cells. PC12 cells were exposed for 18 h to TNFα (0-100 ng/ml), to H2O2 (1-300 μM) or to both, each at sub-toxic concentrations. Lactic dehydrogenase release, prostaglandin E2 accumulation and morphology indicated cell death and stress response. TNFα toxicity was seen at >50 ng/ml, and that of H2O 2 at >150 μM, however, when together, sub-lethal levels (25 ng/ml TNFα and 30 μM H2O2) induced toxicity. Dexanabinol, an N-methyl-D-aspartate antagonist with antioxidant and anti-TNFα properties, completely rescued the cells. These findings corroborate our hypothesis on the cooperative toxicity exerted by TNFα and ROS after brain injury.
AB - Tumor necrosis factor-α (TNFα) is harmful in the early phase and beneficial in the long-term phase after brain injury. Reactive oxygen species (ROS) are among the most toxic mediators activated by injury. We speculate that part of the TNFα toxicity is mediated by its synergism with ROS. Thus, toxicity of TNFα and ROS, alone or together, were studied in PC12 cells. PC12 cells were exposed for 18 h to TNFα (0-100 ng/ml), to H2O2 (1-300 μM) or to both, each at sub-toxic concentrations. Lactic dehydrogenase release, prostaglandin E2 accumulation and morphology indicated cell death and stress response. TNFα toxicity was seen at >50 ng/ml, and that of H2O 2 at >150 μM, however, when together, sub-lethal levels (25 ng/ml TNFα and 30 μM H2O2) induced toxicity. Dexanabinol, an N-methyl-D-aspartate antagonist with antioxidant and anti-TNFα properties, completely rescued the cells. These findings corroborate our hypothesis on the cooperative toxicity exerted by TNFα and ROS after brain injury.
KW - Oxidative stress
KW - PC12 cells
KW - Reactive oxygen species
KW - Tumor necrosis factor-α
UR - http://www.scopus.com/inward/record.url?scp=0345096625&partnerID=8YFLogxK
U2 - 10.1016/j.neulet.2003.09.023
DO - 10.1016/j.neulet.2003.09.023
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C2 - 14664914
AN - SCOPUS:0345096625
SN - 0304-3940
VL - 353
SP - 115
EP - 118
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 2
ER -