title: Axin expression reduces staurosporine-induced mitochondria-mediated cell death in HeLa cells.
abstract: Cytoplasmic axin expression frequently produces punctuate structures in cells, but the nature of axin puncta has not been fully elucidated. In an effort to analyze cytoplasmic axin puncta, we established HeLa cells expressing axin in a doxycycline-inducible manner (HeLa-Axin). We observed that axin accumulated in an aggregate-like pattern in perinuclear areas and appeared to be associated with mitochondria, Golgi apparatus, and endoplasmic reticulum (ER), but not lysosomes. Further biochemical analysis suggested that some part of the cytoplasmic axin pool was associated with mitochondria. In addition, mitochondrial proteins [i.e., cytochrome oxidase IV (CoxIV) and cytochrome c] were slightly higher in HeLa-Axin cells than in HeLa-EV cells, suggesting altered mitochondrial degradation. HeLa-Axin cells were then treated with staurosporine (STS) to determine if the mitochondria-induced apoptosis pathway was altered. Compared to STS-treated control cells (HeLa-EV), HeLa-Axin cells had less STS-induced cytotoxicity and reduced caspase-3 activation and PARP cleavage. Given that mitochondria outer membrane potential was unchanged, HeLa-Axin cells might be relatively resistant to STS-mediated mitochondrial damage. Mitochondria associated with axin aggregates were resistant to detergent-mediated permeabilization. These results suggest that axin forms aggregate-like structures in association with mitochondria, which render mitochondria resistant to STS-induced membrane damage and cytotoxicity.
authors: Laboratory of Cell Biology, Department of Microbiology and Bank for Pathogenic Virus, College of Medicine, Korea University, Seoul 136-705, Republic of Korea.
authors: Jee-Hye
authors: JH
authors: Shin
authors: Hyun-wook
authors: HW
authors: Kim
authors: Im Joo
authors: IJ
authors: Rhyu
authors: Ki-Joon
authors: KJ
authors: Song
authors: Sun-Ho
authors: SH
authors: Kee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D060466:Axin Protein / Q000235:genetics* / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D019311:Staurosporine / Q000494:pharmacology*
chemical_list: D060466:Axin Protein; D004791:Enzyme Inhibitors; D045304:Cytochromes c; D003576:Electron Transport Complex IV; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D019311:Staurosporine