Abstract |
In the present study, we used mitochondrial DNA-depleted Jurkat subclones (rho0 cells) to demonstrate that Fas agonistic Ab (CH-11), at the concentrations that evoke apoptotic death of the parental Jurkat cells, induced necrosis mainly through generation of excess reactive oxygen species, lysosomal rupture, and sequential activation of cathepsins B and D, and in minor part through activation of receptor-interacting protein (RIP). In the rho0 cells treated with CH-11, ATP supplementation converted necrosis into apoptosis by the formation of the apoptosome and subsequent activation of procaspase-3. In these ATP-supplemented rho0 cells (ATP-rho0), generation of excess ROS and lysosomal rupture were still seen, yet cathepsins B and D were inactivated and RIP was degraded. The conversion of necrosis to apoptosis, RIP degradation, and cathepsin inactivation in ATP- rho0 cells were blocked by caspase-3 inhibitors. Activities of cathepsins B and D in the lysate of necrotic rho0 cells were inhibited by the addition of apoptotic parental Jurkat cell lysate. Thus, apoptosis may supercede necrosis.
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Authors | Tsutomu Sato, Takuro Machida, Sho Takahashi, Kazuyuki Murase, Yutaka Kawano, Tsuyoshi Hayashi, Satoshi Iyama, Kohich Takada, Kageaki Kuribayashi, Yasushi Sato, Masayoshi Kobune, Rishu Takimoto, Takuya Matsunaga, Junji Kato, Yoshiro Niitsu |
Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 181
Issue 1
Pg. 197-207
(Jul 01 2008)
ISSN: 0022-1767 [Print] United States |
PMID | 18566385
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies
- CH-11 anti-fas antibody, human
- DNA, Mitochondrial
- Reactive Oxygen Species
- fas Receptor
- Adenosine Triphosphate
- Receptor-Interacting Protein Serine-Threonine Kinases
- Caspase 3
- Caspase 9
- Cathepsin B
- Cathepsin D
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Topics |
- Adenosine Triphosphate
(metabolism)
- Antibodies
(immunology)
- Apoptosis
- Caspase 3
(metabolism)
- Caspase 9
(metabolism)
- Cathepsin B
(antagonists & inhibitors, metabolism)
- Cathepsin D
(antagonists & inhibitors, metabolism)
- DNA, Mitochondrial
(genetics)
- Humans
- Jurkat Cells
- Lipid Metabolism
- Lysosomes
(enzymology)
- Necrosis
- Oxidation-Reduction
- Reactive Oxygen Species
(metabolism)
- Receptor-Interacting Protein Serine-Threonine Kinases
(metabolism)
- fas Receptor
(immunology, metabolism)
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