Achacin induces cell death in HeLa cells through two different mechanisms

Achacin, which belongs to the l-amino acid oxidase group, oxidizes free amino acids and produces hydrogen peroxide in cell culture systems. Morphological changes in cells incubated with achacin were similar to those of cells incubated with H 2O 2. In both cases, the end result was cell death. To exa...

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Bibliographic Details
Published in:Archives of biochemistry and biophysics 2004-02, Vol.422 (1), p.103-109
Main Authors: Kanzawa, Nobuyuki, Shintani, Satoko, Ohta, Kazumasa, Kitajima, Seiji, Ehara, Tatsuya, Kobayashi, Hiroko, Kizaki, Harutoshi, Tsuchiya, Takahide
Format: Article
Language:English
Subjects:
Achacin
Amino Acid Chloromethyl Ketones - pharmacology
Amino Acid Oxidoreductases - metabolism
Amino Acids - analysis
Amino Acids - chemistry
Amino Acids - deficiency
Amino Acids - metabolism
Apoptosis
Apoptosis - drug effects
Apoptosis - physiology
Caspase Inhibitors
Caspases - metabolism
Cell Survival - drug effects
Cell Survival - physiology
Chromosomes - drug effects
Cysteine Proteinase Inhibitors - pharmacology
DNA Fragmentation - drug effects
DNA Fragmentation - physiology
HeLa Cells
Humans
Hydrogen peroxide
Hydrogen Peroxide - pharmacology
L-Amino Acid Oxidase
Neuropeptides - metabolism
Neuropeptides - pharmacology
Oxidation-Reduction
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Summary:Achacin, which belongs to the l-amino acid oxidase group, oxidizes free amino acids and produces hydrogen peroxide in cell culture systems. Morphological changes in cells incubated with achacin were similar to those of cells incubated with H 2O 2. In both cases, the end result was cell death. To examine the mechanism of achacin-associated cytotoxicity, the H 2O 2 scavenger catalase was added to culture media. Features typical of apoptosis, including morphological changes, DNA fragmentation, and PARP cleavage, were observed when cells were incubated with achacin in the presence of catalase. Moreover, apoptosis was inhibited by Z–VAD–fmk, a broad-spectrum caspase inhibitor. Herein, we present evidence that two pathways are involved in achacin-induced cell death. One is direct generation of H 2O 2 through the l-amino acid oxidase activity of achacin. The other is the caspase-mediated apoptotic pathway that is induced by depletion of l-amino acids by achacin.
ISSN:0003-9861
1096-0384
DOI:10.1016/j.abb.2003.12.007