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Inhibition of PP2A and the consequent activation of JNK/c‐Jun are involved in tributyltin‐induced apoptosis in human amnionic cells
Author(s) -
Zhang Yali,
Liang Jing,
Sun Lijun,
Guo Zonglou,
Xu Lihong
Publication year - 2013
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.20730
Subject(s) - tributyltin , apoptosis , c jun , chemistry , microbiology and biotechnology , biology , biochemistry , environmental chemistry , gene , transcription factor
Tributyltin (TBT), a highly toxic environmental contaminant, has been shown to induce mitochondrial‐dependent apoptosis in several mammalian cells. However, the upstream signal transduction pathways involved in TBT‐induced apoptosis are still not fully elucidated. In this study, the protein phosphatase (PP) 2A, microtubule organization, and mitogen‐activated protein kinases (MAPKs), including JNK, p38 and their downstream transcription factors, c‐Jun and ATF‐2, respectively, were investigated in human amnionic cells treated by TBT. Furthermore, the activation of procaspase‐3 after blocking either one of these MAPK pathways was also observed. The results showed that TBT effectively induced apoptosis characterized by caspase‐3 activation. In apoptotic cells, the inhibition of PP2A activity and microtubule depolymerization was detected. Additionally, JNK and p38, as well as their downstream targets, c‐Jun and ATF‐2, were activated. Moreover, a JNK inhibitor, but not p38 inhibitor, significantly reduced caspase‐3 activation. It can be concluded that the inhibition of PP2A may (1) play as a role in the activation of JNK and c‐Jun and the concomitant promotion of microtubule depolymerization and (2) lead to the activation of caspase‐3 in TBT‐induced apoptotic cells. The results of this study suggest a critical role of PP2A in the TBT toxicity mechanism. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2013.