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Status: Bibliographieeintrag

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Verfasst von:Gdynia, Georg [VerfasserIn]   i
 Keith, Martina [VerfasserIn]   i
 Kopitz, Jürgen [VerfasserIn]   i
 Bergmann, Marion [VerfasserIn]   i
 Faßl, Anne [VerfasserIn]   i
 Weber, Alexander N. R. [VerfasserIn]   i
 George, Julie [VerfasserIn]   i
 Kees, Tim Steffen [VerfasserIn]   i
 Zentgraf, Hanswalter [VerfasserIn]   i
 Wiestler, Otmar D. [VerfasserIn]   i
 Schirmacher, Peter [VerfasserIn]   i
 Roth, Wilfried [VerfasserIn]   i
Titel:Danger signaling protein HMGB1 induces a distinct form of cell death accompanied by formation of giant mitochondria
Verf.angabe:Georg Gdynia, Martina Keith, Jürgen Kopitz, Marion Bergmann, Anne Fassl, Alexander N.R. Weber, Julie George, Tim Kees, Hans-Walter Zentgraf, Otmar D. Wiestler, Peter Schirmacher, and Wilfried Roth
E-Jahr:2010
Jahr:2010 Oct 19
Umfang:11 S.
Fussnoten:Gesehen am 21.02.2023
Titel Quelle:Enthalten in: Cancer research
Ort Quelle:Philadelphia, Pa. : AACR, 1916
Jahr Quelle:2010
Band/Heft Quelle:70(2010), 21, Seite 8558-8568
ISSN Quelle:1538-7445
Abstract:Cells dying by necrosis release the high-mobility group box 1 (HMGB1) protein, which has immunostimulatory effects. However, little is known about the direct actions of extracellular HMGB1 protein on cancer cells. Here, we show that recombinant human HMGB1 (rhHMGB1) exerts strong cytotoxic effects on malignant tumor cells. The rhHMGB1-induced cytotoxicity depends on the presence of mitochondria and leads to fast depletion of mitochondrial DNA, severe damage of the mitochondrial proteome by toxic malondialdehyde adducts, and formation of giant mitochondria. The formation of giant mitochondria is independent of direct nuclear signaling events, because giant mitochondria are also observed in cytoplasts lacking nuclei. Further, the reactive oxygen species scavenger N-acetylcysteine as well as c-Jun NH(2)-terminal kinase blockade inhibited the cytotoxic effect of rhHMGB1. Importantly, glioblastoma cells, but not normal astrocytes, were highly susceptible to rhHMGB1-induced cell death. Systemic treatment with rhHMGB1 results in significant growth inhibition of xenografted tumors in vivo. In summary, rhHMGB1 induces a distinct form of cell death in cancer cells, which differs from the known forms of apoptosis, autophagy, and senescence, possibly representing an important novel mechanism of specialized necrosis. Further, our findings suggest that rhHMGB1 may offer therapeutic applications in treatment of patients with malignant brain tumors.
DOI:doi:10.1158/0008-5472.CAN-10-0204
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DOI: https://doi.org/10.1158/0008-5472.CAN-10-0204
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Acetylcysteine
 Animals
 Apoptosis
 Astrocytes
 Blotting, Western
 Cell Line, Tumor
 Cell Nucleus
 Cell Proliferation
 Electrophoresis, Gel, Two-Dimensional
 Female
 Fluorescent Antibody Technique
 Free Radical Scavengers
 Glioblastoma
 HMGB1 Protein
 Humans
 JNK Mitogen-Activated Protein Kinases
 Membrane Potential, Mitochondrial
 Mice
 Mice, Nude
 Mitochondria
 Mitochondrial Proteins
 Necrosis
 Proteome
 Reactive Oxygen Species
 Signal Transduction
 Tumor Cells, Cultured
K10plus-PPN:1837231664
Verknüpfungen:→ Zeitschrift

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