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N‐(1‐pyrenyl) maleimide induces Bak oligomerization and mitochondrial dysfunction in Jurkat cells (1010.4)
Author(s) -
Wang TzuChien,
Huang PeiRong,
Pao ChiaChu
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1010.4
Subject(s) - jurkat cells , apoptosis , cytochrome c , mitochondrion , microbiology and biotechnology , programmed cell death , chemistry , cytosol , caspase , cytotoxic t cell , biology , biochemistry , t cell , enzyme , immunology , in vitro , immune system
N‐(1‐pyrenyl) maleimide (NPM) has been recently identified as a telomerase inhibitor in a cell‐free system and shown to display a great differential cytotoxicity against hematopoietic cancer cells. However, the primary cytotoxic effect of NPM against hematopoietic cancer cells is induction of apoptosis, rather than inhibition of telomerase. In this study, the molecular mechanism by which NPM induces apoptosis was examined. Here, we show that treatment of Jurkat cells with NPM leads to Bak oligomerization, loss of mitochondrial membrane potential (Δψm), and release of cytochrome C from mitochondria to cytosol. Induction of Bak oligomerization appears to play a critical role in NPM‐induced apoptosis, as down‐regulation of Bak by shRNA significantly prevented NPM‐induced apoptosis in Jurkat cells. Inhibition of caspase‐8 by Z‐IETD‐FMK and/or depletion of Bid did not affect NPM‐induced oligomerization of Bak. Taken together, these results suggest that NPM‐induced apoptosis is mediated through induction of Bak oligomerization and mitochondrial dysfunction by a pathway that is independent of caspase‐8 activation.