title: N-(1-pyrenyl) maleimide induces bak oligomerization and mitochondrial dysfunction in Jurkat Cells.
abstract: N-(1-pyrenyl) maleimide (NPM) is a fluorescent reagent that is frequently used as a derivatization agent for the detection of thio-containing compounds. NPM has been shown to display a great differential cytotoxicity against hematopoietic cancer cells. 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 downregulation of Bak by shRNA significantly prevented NPM-induced apoptosis. 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 a pathway that is independent of caspase-8 activation.
authors: Department of Molecular and Cellular Biology, College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan 333, Taiwan.
authors: Pei-Rong
authors: PR
authors: Huang
authors: Health Sciences Research Institute and School of Natural Sciences, University of California, Merced, CA 95343, USA.
authors: Shu-Chen
authors: SC
authors: Hung
authors: Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan 333, Taiwan.
authors: Chia-Chu
authors: CC
authors: Pao
authors: Department of Molecular and Cellular Biology, College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan 333, Taiwan ; Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan 333, Taiwan.
authors: Tzu-Chien V
authors: TC
authors: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D019169:Jurkat Cells; D008301:Maleimides / Q000494:pharmacology*; D008928:Mitochondria / Q000378:metabolism*; D055503:Protein Multimerization / Q000187:drug effects*; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; D008301:Maleimides; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; C003944:N-(3-pyrene)maleimide; D053181:Caspase 8
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