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Tea polyphenol epigallocatechin 3‐gallate impedes the anti‐apoptotic effects of low‐grade repetitive stress through inhibition of Akt and NFκB survival pathways
Author(s) -
Sen Prosenjit,
Chakraborty Prabir Kumar,
Raha Sanghamitra
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.12.013
Subject(s) - protein kinase b , apoptosis , oxidative stress , kinase , epigallocatechin gallate , chemistry , ly294002 , phosphorylation , pi3k/akt/mtor pathway , biology , pharmacology , biochemistry , polyphenol , antioxidant
V79 Chinese Hamster lung fibroblasts were subjected to repetitive low‐grade stress through multiple exposures to 30 μM H 2 O 2 in culture for 4 weeks. Akt/protein kinase B became phosphorylated at serine 473 and threonine 308 during this period of repetitive stress. Concurrent exposure of the cells to LY294002 (5 μM), a phosphoinositide‐3 kinase inhibitor or 4.5 μM epigallocatechin 3‐gallate (EGCG), a tea polyphenol almost completely blocked Akt activation by repetitive stress. Phosphorylation of I kappa B kinase (IKK) and transcriptional activity driven by nuclear factor kappa B (NFκB) were significantly enhanced by repetitive oxidative stress. These increases were largely abolished by simultaneous exposure to EGCG. The repetitively stressed cells demonstrated a significant resistance to apoptosis by subsequent acute stress in the form of ultraviolet radiation at 5 J/m 2 or H 2 O 2 (7.5 mM). The resistance to apoptosis conferred by repetitive stress was drastically reduced (>80%) by constant exposure to EGCG during the stress period while the presence of LY294002 or the NFκB inhibitor SN50 brought about a relatively moderate effect (about 50–65%). Our data indicate that activation of Akt and NFκB pro‐survival pathways by repetitive low‐grade stress results in a strong inhibition of the normal apoptotic response after subsequent acute stress. The tea polyphenol EGCG impedes the activation of both Akt and NFκB by repetitive stress and as a result preserves the normal apoptotic response during subsequent acute stress.