Title |
S100A8/9 induces cell death via a novel, RAGE-independent pathway that involves selective release of Smac/DIABLO and Omi/HtrA2
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Published in |
Biochimica et Biophysica Acta (BBA), November 2007
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DOI | 10.1016/j.bbamcr.2007.10.015 |
Pubmed ID | |
Authors |
Saeid Ghavami, Claus Kerkhoff, Walter J. Chazin, Kamran Kadkhoda, Wenyan Xiao, Anne Zuse, Mohammad Hashemi, Mehdi Eshraghi, Klaus Schulze-Osthoff, Thomas Klonisch, Marek Los |
Abstract |
A complex of two S100 EF-hand calcium-binding proteins S100A8/A9 induces apoptosis in various cells, especially tumor cells. Using several cell lines, we have shown that S100A8/A9-induced cell death is not mediated by the receptor for advanced glycation endproducts (RAGE), a receptor previously demonstrated to engage S100 proteins. Investigation of cell lines either deficient in, or over-expressing components of the death signaling machinery provided insight into the S100A8/A9-mediated cell death pathway. Treatment of cells with S100A8/A9 caused a rapid decrease in the mitochondrial membrane potential (DeltaPsi(m)) and activated Bak, but did not cause release of apoptosis-inducing factor (AIF), endonuclease G (Endo G) or cytochrome c. However, both Smac/DIABLO and Omi/HtrA2 were selectively released into the cytoplasm concomitantly with a decrease in Drp1 expression, which inhibits mitochondrial fission machinery. S100A8/A9 treatment also resulted in decreased expression of the anti-apoptotic proteins Bcl2 and Bcl-X(L), whereas expression of the pro-apoptotic proteins Bax, Bad and BNIP3 was not altered. Over-expression of Bcl2 partially reversed the cytotoxicity of S100A8/A9. Together, these data indicate that S100A8/A9-induced cell death involves Bak, selective release of Smac/DIABLO and Omi/HtrA2 from mitochondria, and modulation of the balance between pro- and anti-apoptotic proteins. |
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Czechia | 1 | 2% |
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Japan | 1 | 2% |
United States | 1 | 2% |
Unknown | 52 | 90% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 17 | 29% |
Researcher | 13 | 22% |
Student > Master | 5 | 9% |
Student > Doctoral Student | 4 | 7% |
Student > Bachelor | 3 | 5% |
Other | 11 | 19% |
Unknown | 5 | 9% |
Readers by discipline | Count | As % |
---|---|---|
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Biochemistry, Genetics and Molecular Biology | 11 | 19% |
Medicine and Dentistry | 10 | 17% |
Pharmacology, Toxicology and Pharmaceutical Science | 5 | 9% |
Immunology and Microbiology | 4 | 7% |
Other | 4 | 7% |
Unknown | 9 | 16% |