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Inhibition of cell death by a novel 16.2 kD heat shock protein predominantly via Hsp90 mediated lipid rafts stabilization and Akt activation pathway

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Abstract

AlphaB-crystallin homology, heat stress induction and chaperone activity suggested that a previously encloned gene product is a novel small heat shock protein (Hsp16.2). Suppression of Hsp16.2 by siRNA sensitized cells to hydrogen peroxide or taxol induced cell-death. Over-expressing of Hsp16.2 protected cells against stress stimuli by inhibiting cytochrome c release from the mitochondria, nuclear translocation of AIF and endonuclease G, and caspase 3 activation. Recombinant Hsp16.2 protected mitochondrial membrane potential against calcium induced collapse in vitro indicating that Hsp16.2 stabilizes mitochondrial membrane systems. Hsp16.2 formed self-aggregates and bound to Hsp90. Inhibition of Hsp90 by geldanamycin diminished the cytoprotective effect of Hsp16.2 indicating that this effect was Hsp90-mediated. Hsp16.2 over-expression increased lipid rafts formation as demonstrated by increased cell surface labeling with fluorescent cholera toxin B, and increased Akt phosphorylation. The inhibition of PI-3-kinase—Akt pathway by LY-294002 or wortmannin significantly decreased the protective effect of the Hsp16.2. These data indicate that the over-expression of Hsp16.2 inhibits cell death via the stabilization of mitochondrial membrane system, activation of Hsp90, stabilization of lipid rafts and by the activation of PI-3-kinase—Akt cytoprotective pathway.

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Authors and Affiliations

  1. Department of Biochemistry and Medical Chemistry, University of Pécs, 12 Szigeti Street, Pécs, H-7624, Hungary

    Szabolcs Bellyei, Andras Szigeti, Arpad Boronkai, Eva Pozsgai, Zita Bognar, Eniko Hocsak, Balazs Sumegi & Ferenc Gallyas Jr

  2. Department of Oncotherapy, University of Pécs, Pécs, Hungary

    Szabolcs Bellyei, Andras Szigeti & Arpad Boronkai

  3. Department of Pathology, University of Pécs, Pécs, Hungary

    Eva Gomori

  4. Department of Medical Genetics and Child Development, University of Pécs, Pécs, Hungary

    Bela Melegh

  5. Department of Medical Chemistry, University of Szeged, Szeged, Hungary

    Tamas Janaky

  6. Research group for mitochondrial function and mitochondrial diseases, Hungarian Academy of Sciences, Pécs, Hungary

    Balazs Sumegi

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  1. Szabolcs Bellyei
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Correspondence to Balazs Sumegi.

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Bellyei, S., Szigeti, A., Boronkai, A. et al. Inhibition of cell death by a novel 16.2 kD heat shock protein predominantly via Hsp90 mediated lipid rafts stabilization and Akt activation pathway. Apoptosis 12, 97–112 (2007). https://doi.org/10.1007/s10495-006-0486-x

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  • DOI: https://doi.org/10.1007/s10495-006-0486-x

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