Taurine monochloramine activates a cell death pathway involving Bax and Caspase-9

Derek K Emerson; Michael L McCormick; Jennifer A Schmidt; C Michael Knudson

doi:10.1074/jbc.M411672200

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Taurine monochloramine activates a cell death pathway involving Bax and Caspase-9

Journal article

Open access

Peer reviewed

Taurine monochloramine activates a cell death pathway involving Bax and Caspase-9

Derek K Emerson, Michael L McCormick, Jennifer A Schmidt and C Michael Knudson

The Journal of biological chemistry, Vol.280(5), pp.3233-3241

02/04/2005

DOI: 10.1074/jbc.M411672200

PMID: 15545281

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Abstract

Taurine is an abundant free amino acid that interacts with the potent oxidant hypochlorous acid to form the less toxic and more stable oxidant taurine monochloramine (TauNHCl). TauNHCl has diverse cellular effects ranging from inhibiting the production of proinflammatory mediators to inhibiting cell proliferation and inducing cell death. We hypothesized that TauNHCl could activate a cell death pathway involving Bcl-2 members and the activation of caspase proteases. FL5.12 cells are lymphocytic cells that undergo apoptosis following interleukin-3 (IL-3) withdrawal. Therefore, cell death following TauNHCl treatment of FL5.12 cells was compared and contrasted with IL-3 withdrawal. We found that TauNHCl treatment activates a cell death pathway with kinetics very similar to IL-3 withdrawal. TauNHCl-treated cells undergo an annexin V-positive/propidium iodide-negative phase of death consistent with apoptosis. TauNHCl treatment results in a conformational change in BAX that is associated with its activation. Both Bcl-2 and, to a lesser degree, the dominant negative form of caspase-9 inhibit cell death following TauNHCl treatment. In contrast with IL-3 withdrawal, TauNHCl treatment of FL5.12 cells results in a rapid cell cycle arrest that is cell cycle phase-independent. These results demonstrate that TauNHCl treatment induces a rapid, cell cycle-independent proliferative arrest followed by the activation of a cell death pathway involving Bcl-2 family members and caspase activation.

Cell Line

Cell Survival - drug effects

Taurine - analogs & derivatives

B-Lymphocytes - cytology

Caspase 9

bcl-2-Associated X Protein

Cell Division - drug effects

B-Lymphocytes - drug effects

Proto-Oncogene Proteins c-bcl-2 - metabolism

Animals

Caspases - metabolism

Inflammation Mediators - pharmacology

Clone Cells

Mice

Cell Death - drug effects

Taurine - pharmacology

Details

Title: Subtitle: Taurine monochloramine activates a cell death pathway involving Bax and Caspase-9
Creators: Derek K Emerson - Department of Pathology, The University of Iowa Roy J. and Lucille P. Carver College of Medicine, Iowa City, Iowa 52242, USA
Michael L McCormick
Jennifer A Schmidt
C Michael Knudson
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.280(5), pp.3233-3241
DOI: 10.1074/jbc.M411672200
PMID: 15545281
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Language: English
Date published: 02/04/2005
Academic Unit: Pathology; Radiation Oncology
Record Identifier: 9984046904002771

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