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Tournefolic acid B methyl ester attenuates glutamate‐induced toxicity by blockade of ROS accumulation and abrogating the activation of caspases and JNK in rat cortical neurons
Author(s) -
Chi ChihWen,
Wang ChuenNeu,
Lin YunLian,
Chen ChiehFu,
Shiao YoungJi
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.02912.x
Subject(s) - glutamate receptor , neurotoxicity , neuroprotection , biochemistry , reactive oxygen species , chemistry , programmed cell death , caspase , kinase , toxicity , antioxidant , apoptosis , pharmacology , biology , microbiology and biotechnology , receptor , organic chemistry
The effects of nine polyphenolic compounds on glutamate‐mediated toxicity were investigated. The underlying mechanisms by which a polyphenolic compound confers its effect were also elucidated. Treatment of cortical neurons with 50 µ m glutamate for 24 h decreased cell viability by 45.8 ± 7.9%, and 50 µ m of tournefolic acid B methyl ester attenuated glutamate‐induced cell death by 46.8 ± 17.8%. Glutamate increased the activity of caspase 35.2‐fold, and to a similar extent for caspase 2, 6, 8 and 9. Tournefolic acid B methyl ester abrogated glutamate‐induced activation of caspase 2, 3, 6 and 9 by about 70%, and to a lesser extent for caspase 8. Treatment with glutamate for 1 h elevated reactive oxygen species (ROS) by 208.3 ± 21.3%. Tournefolic acid B methyl ester eliminated the glutamate‐induced accumulation of ROS. Glutamate increased the phosphorylation of p54‐c‐jun N‐terminal kinase (JNK) concomitantly with activation of the endogenous antioxidant defense system. Tournefolic acid B methyl ester at 50 µ m diminished the activity of p54‐JNK in control and glutamate‐treated cells, coinciding with the abolishment of the glutamate‐triggered antioxidant defense system. Therefore, tournefolic acid B methyl ester blocked the activation of the caspase cascade, eliminated ROS accumulation and abrogated the activation of JNK, thereby conferring a neuroprotective effect on glutamate‐mediated neurotoxicity.