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S100A8/9 induces ce...
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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- Ghavami, Saeid (author)
- Department of Biochemistry and Medical Genetics, Manitoba Institute of Cell Biology, Cancer Care Manitoba, Winnipeg, Manitoba, Canada
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- Kerkhoff, Claus (author)
- Institute of Experimental Dermatology, Münster, Germany
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- Chazin, Walter J. (author)
- Department of Biochemistry Vanderbilt University, Nashville, USA; Department of Chemistry, Vanderbilt University, Nashville, USA; Center for Structural Biology, Vanderbilt University, Nashville, TN 37232-8725, USA
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- Kadhoka, Kamran (author)
- Manitoba Institute of Cell Biology, Canada; Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Canada
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- Xiao, Wenyan (author)
- Manitoba Institute of Cell Biology, Canada
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- Zusea, Anne (author)
- Manitoba Institute of Cell Biology, Canada; Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Canada
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- Hashemi, Mohammad (author)
- Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Science, Zahedan, Iran
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- Eshraghi, Mehdi (author)
- Manitoba Institute of Cell Biology, Canada b Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Canada
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- Schulze-Osthoff, Klaus (author)
- Institute of Molecular Medicine, University of Düsseldorf, Düsseldorf, Germany
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- Klonisch, Thomas (author)
- Department of Human Anatomy and Cell Sciences, and Manitoba Institute of Child Health, Winnipeg, Canada
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- Los, Marek Jan (author)
- Manitoba Institute of Cell Biology, Canada; Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Canada; BioApplications Enterprises, Winnipeg, MB, Canada
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(creator_code:org_t)
- Elsevier, 2008
- 2008
- English.
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In: Biochimica et Biophysica Acta. Molecular Cell Research. - : Elsevier. - 0167-4889 .- 1879-2596. ; 1783:2, s. 297-311
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Abstract
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- 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 (ΔΨm) 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-XL, 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- Bcl2 protein family; S100/calgranulin; Cancer regression; Drp1; Receptor for advanced glycated endproducts (RAGE); Mitochondrial fission; XIAP
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Ghavami, Saeid
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Kerkhoff, Claus
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Chazin, Walter J ...
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Kadhoka, Kamran
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Xiao, Wenyan
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Zusea, Anne
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show more...
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Hashemi, Mohamma ...
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Eshraghi, Mehdi
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Schulze-Osthoff, ...
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Klonisch, Thomas
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Los, Marek Jan
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Cell Biology
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
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Biochimica et Bi ...
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Linköping University