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Article

XIAP impairs mitochondrial function during apoptosis by regulating the Bcl-2 family in renal cell carcinoma

  • Authors:
    • Chao Chen
    • Tian Shu Liu
    • Si Cong Zhao
    • Wen Zheng Yang
    • Zong Ping Chen
    • Yong Yan
  • View Affiliations / Copyright

    Affiliations: Department of Urology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, P.R. China, Department of Anesthesiology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, P.R. China, Department of Urology, The Affiliated Hospital of Zunyi Medical College, Zunyi 563000, P.R. China
  • Pages: 4587-4593
    |
    Published online on: March 20, 2018
       https://doi.org/10.3892/etm.2018.5974
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Abstract

Efficient apoptosis requires Bcl-2 family-mediated mitochondrial outer membrane permeabilization (MOMP), which releases pro‑apoptotic proteins to the cytosol, activating apoptosis and inhibiting X‑linked inhibitor of apoptosis protein (XIAP). XIAP is a member of the inhibitors of apoptosis protein family whose expression is elevated in many cancer types and participates in the release of pro‑apoptotic proteins. To explore the association between XIAP and the Bcl‑2 family, and the influence of XIAP on mitochondria, RNA interference of XIAP was performed in Caki‑1 cells and the dynamic change in the levels of related proteins was compared with the original Caki‑1 cells upon induction of apoptosis. Upon knockdown of XIAP, the release of cytochrome c (Cyt‑c), second mitochondria‑derived activator of caspase (Smac) and apoptotic protease activating factor 1 (Apaf‑1) from mitochondria proceeded normally, whereas in Caki‑1 cells, the release of these pro‑apoptotic proteins was significantly prolonged, and incomplete. Downregulation of XIAP through small interfering RNA resulted in an increase of apoptosis and a marked decrease in Bcl‑2 and Bcl‑xl levels at 3 h. Additionally, the regulation of the level of XIAP protein affected the specific ratios of Bcl‑2/Bax and Bcl‑xl/Bax, which play decisive roles in cell death. In the present study, it was revealed that XIAP can feed back to mitochondria, delaying Cyt‑c and Apaf‑1 release. Furthermore, XIAP can limit the release of its inhibitor Smac with the involvement of Bcl-2 family proteins.
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Copy and paste a formatted citation
Spandidos Publications style
Chen C, Liu TS, Zhao SC, Yang WZ, Chen ZP and Yan Y: XIAP impairs mitochondrial function during apoptosis by regulating the Bcl-2 family in renal cell carcinoma. Exp Ther Med 15: 4587-4593, 2018.
APA
Chen, C., Liu, T.S., Zhao, S.C., Yang, W.Z., Chen, Z.P., & Yan, Y. (2018). XIAP impairs mitochondrial function during apoptosis by regulating the Bcl-2 family in renal cell carcinoma. Experimental and Therapeutic Medicine, 15, 4587-4593. https://doi.org/10.3892/etm.2018.5974
MLA
Chen, C., Liu, T. S., Zhao, S. C., Yang, W. Z., Chen, Z. P., Yan, Y."XIAP impairs mitochondrial function during apoptosis by regulating the Bcl-2 family in renal cell carcinoma". Experimental and Therapeutic Medicine 15.5 (2018): 4587-4593.
Chicago
Chen, C., Liu, T. S., Zhao, S. C., Yang, W. Z., Chen, Z. P., Yan, Y."XIAP impairs mitochondrial function during apoptosis by regulating the Bcl-2 family in renal cell carcinoma". Experimental and Therapeutic Medicine 15, no. 5 (2018): 4587-4593. https://doi.org/10.3892/etm.2018.5974
Copy and paste a formatted citation
x
Spandidos Publications style
Chen C, Liu TS, Zhao SC, Yang WZ, Chen ZP and Yan Y: XIAP impairs mitochondrial function during apoptosis by regulating the Bcl-2 family in renal cell carcinoma. Exp Ther Med 15: 4587-4593, 2018.
APA
Chen, C., Liu, T.S., Zhao, S.C., Yang, W.Z., Chen, Z.P., & Yan, Y. (2018). XIAP impairs mitochondrial function during apoptosis by regulating the Bcl-2 family in renal cell carcinoma. Experimental and Therapeutic Medicine, 15, 4587-4593. https://doi.org/10.3892/etm.2018.5974
MLA
Chen, C., Liu, T. S., Zhao, S. C., Yang, W. Z., Chen, Z. P., Yan, Y."XIAP impairs mitochondrial function during apoptosis by regulating the Bcl-2 family in renal cell carcinoma". Experimental and Therapeutic Medicine 15.5 (2018): 4587-4593.
Chicago
Chen, C., Liu, T. S., Zhao, S. C., Yang, W. Z., Chen, Z. P., Yan, Y."XIAP impairs mitochondrial function during apoptosis by regulating the Bcl-2 family in renal cell carcinoma". Experimental and Therapeutic Medicine 15, no. 5 (2018): 4587-4593. https://doi.org/10.3892/etm.2018.5974
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