[Translocation of orphan receptor TR3 from nuclei to mitochondria induced by staurosporine].
OBJECTIVE
Staurosporine (STS), a non- specific protein kinase inhibitor, can extensively induce cell apoptosis. Orphan receptor TR3, an immediate-early response gene, belongs to the steroid/thyroid receptor superfamily. After stimulated by apoptosis-inducing agents, TR3 is expressed rapidly and translocates from nuclei to mitochondria,which finally induces cell apoptosis. This study was to investigate the mechanism by which STS induces apoptosis of gastric cancer cell line BGC-823,and its correlation with translocation of TR3 in BGC-823 cells.


METHODS
Fluorescent microscopy was used to observe apoptotic morphology of BGC-823 cells after treated with STS for 3 and 24 h and stained by DAPI, and determine cell apoptotic rate. Laser scan confocal microscopy and Western blot were performed to investigate translocation of orphan receptor TR3 and the release of cytochrome c. Flow cytometry and confocal microscopy were used to examine mitochondrial membrane potential.


RESULTS
After treated for 3 h,and 24 h,apoptosis rates of BGC-823 cells in STS-treatment groups were higher than those of cells in control groups (15.7% vs. 4.0%, and 39.4% vs. 4.7%). After BGC-823 cells exposed to STS for 3 h,TR3 translocated from nuclei to mitochondria, mitochondrial membrane potential was decreased, and cytochrome c released from mitochondria to the cytoplasm.


CONCLUSIONS
TR3, in response to STS, translocates from nuclei to cytoplasm, where it targets to mitochondria to induce cytochrome c release, finally results in apoptosis of gastric cancer cells.
Zhan
Yan-Yan
YY
Key Laboratory of Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, P.R. China.
Wu
Qiao
Q
D021581:Active Transport, Cell Nucleus; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism*; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D011987:Receptors, Steroid / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000473:pathology
D004791:Enzyme Inhibitors; C539821:NR4A1 protein, human; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D045304:Cytochromes c; D019311:Staurosporine