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A polypeptide from Chlamys farreri inhibits UVB-induced HaCaT cells apoptosis via the Apaf-1/caspase-9 and Smac/XIAP signaling pathway

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Abstract

A novel marine active polypeptide (PCF), isolated from the gonochoric Chinese scallop, Chlamys farreri, has potential antioxidant and anti-apoptotic activity against ultraviolet irradiation. We investigated whether UVB-induced HaCaT cell apoptosis occurs via the mitochondrial pathways Apaf-1/caspase-9 and Smac/XIAP/caspase-3. We then investigated the molecular mechanisms controlling the anti-apoptotic effect of PCF. Pre-treatment with PCF and caspase-9 inhibitor significantly inhibited UVB-induced apoptosis in HaCaT cells based on a DNA fragmentation assay and Hoechst 33258 staining. The expression of Apaf-1 and the cleavage of procaspase-9 were dose-dependently reduced by 1.42–5.96 mmol/L PCF pretreatment in UVB-irradiated HaCaT cells. This was followed by inhibition of cleavage of procaspase-3, whose activation induced cell apoptosis. Meanwhile, PCF significantly and dose-dependently enhanced the activation of ATPase. Furthermore, we demonstrated that PCF strongly inhibited the release of Smac from the mitochondria to cytosol by reducing the degradation of XIAP dose-dependently. We conclude that the protective effect of PCF against UVB irradiation in HaCaT cells may be attributed to the inhibition of the Apaf-1/caspase-9 and Smac/XIAP/caspase-3 apoptotic signaling pathways.

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References

  • Adrain C, Martin S J. 2001. The mitochondrial apoptosome: A killer unleashed by the cytochrome seas. Trends Biochem Sci., 26: 390–397.

    Article  Google Scholar 

  • Bratton S B, Cohen G M. 2001. Apoptotic death sensor: an organelle’s alter ego? Trends Pharmacol Sci., 22: 306–315.

    Article  Google Scholar 

  • Chai J, Du C, Wu J W, Kyin S, Wang X, Shi Y. 2000. Structural and biochemical basis of apoptotic activation by Smac / DIABLO. Nature, 406: 855–862.

    Article  Google Scholar 

  • Deveraux Q L, Reed J C. 1999. IAP family proteins-suppressors of apoptosis. Genes Dev, 13: 239–252.

    Article  Google Scholar 

  • Deveraux Q L, Roy N, Stennicke H R, Van Arsdale T, Zhou Q, Srinivasula S M, Alnemri E S, Salvesen G S, Reed J C. 1998. IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases. J. Embo., 17: 2 215–2 223.

    Article  Google Scholar 

  • Du C, Fang M, Li Y, Li L, Wang X. 2000. Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell, 102: 33–42.

    Article  Google Scholar 

  • Ekert P G, Silke J, Hawkins C J, Verhagen A M, Vaux D L. 2001. J. Cell Biol., 152, 483–490.

    Article  Google Scholar 

  • Kim H E, Jiang X, Du F, Wang X. 2008. PHAPI, CAS, and Hsp 70 promote apoptosome formation by preventing Apaf-1 aggregation and enhancing nucleotide exchange on Apaf-1. Mol. Cell., 30(2): 239–47.

    Article  Google Scholar 

  • Li B H, Zhou Y B, Guo S B, Wang C B. 2007. Polypeptide from Chlamys farreri inhibits UVB-induced HaCaT cells apoptosis via inhibition CD95 pathway and reactive oxygen species. Free Radic Res., 41(11): 1 224–1 232.

    Article  Google Scholar 

  • Li P, Nijhawan D, Budihardjo I, Srinivasula S M, Ahmad M, Alnemri E S, Wang X. 1997. Cytochrome c and dATP dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell, 91: 479–489.

    Google Scholar 

  • Murphy G, Young A R, Wulf H C, Kulms D, Schwarz T. 2001. The molecular determinants of sunburn cell formation. Exp. Dermatol. 10: 155–160.

    Article  Google Scholar 

  • Nilkantha Sen, Benu Brata Das, Agneyo Ganguly, Tanmoy Mukherjee, Santu Bandyopadhyay, Hemanta K. Majumder. 2004. Camptothecin-induced Imbalance inIntracellular Cation Homeostasis Regulates Programmed Cell Death in Unicellular Hemoflagellate Leishmania donovani. J. Biol. Chem., 279(50): 523 66–52 375.

    Article  Google Scholar 

  • Riedl S J, Salvesen G S. 2007. The apoptosome: signaling platform for cell death, Nat. Rev. Mol. Cell Biol, 8: 405–413.

    Article  Google Scholar 

  • Shimizu S, Narita M, Tsujimoto Y. 1999. Bcl-1 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC. Nature, 399: 483–487.

    Article  Google Scholar 

  • Sitailo L A, Tibudan S S, Denning M F. 2002. Activation of caspase-9 is required for UV-induced apoptosis of human keratinocytes. J. Biol. Chem. 277: 19 346–19 352.

    Article  Google Scholar 

  • Soengas M S, Alarcon R M, Yoshida H, Giaccia A J, Hakem R, Mak T W, Lowe S W. 1999. Apaf-1 and caspase-9 in p53-dependent apoptosis and tumor inhibition. Science, 284(5411): 156–159.

    Article  Google Scholar 

  • Steller H. 1995. Mechanisms and genes of cellular suicide. Science, 267: 1 445–1 449.

    Article  Google Scholar 

  • Suzuki Y, Takahashi-Niki K, Akagi T, Hashikawa T, Takahashi R. 2004. Mitochondrial protease Omi/HtrA2 enhances caspase activation through multiple pathways. Cell Death and Differentiation, 11: 208–216.

    Article  Google Scholar 

  • Takasawa R, Nakamura H, Mori T, Tanuma S. 2005. Differential apoptotic pathways in human keratinocyte HaCaT cells exposed to UVB and UVC. Apoptosis, 10: 1 121–1 130.

    Article  Google Scholar 

  • Takasawa R, Tanuma S. 2003. Sustained release of Smac/DIABLO from mitochondria commits to undergo UVB-induced apoptosis. Apoptosis, 8: 291–299.

    Article  Google Scholar 

  • Wang C B, Huang M Q, Tao G L, Yu G Y, Han Z W, Yang Z H, Wang Y J. 2004. Polypeptide from Chlamys farreri protects HaCaT cells from UVB-induced apoptosis. Chemico-Biological Interactions, 147: 119–127.

    Article  Google Scholar 

  • Wang X Q, Xiao A Y. Christian S, Krzystztof H, Yang A Z, Goldberg M P., Choi D W, Yu S P. 2003. Apoptotic insults impair Na+, K+-ATPase activity as a mechanism of neuronal death mediated by concurrent ATP deficiency and oxidant stress. J. Cell Science, 116: 2 099–2 110

    Google Scholar 

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Correspondence to Chunbo Wang  (王春波).

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Supported by the National Natural Science Foundation of China (No. 30471458), and the Natural Science Foundation of Shandong Province, China (No. Z2007c09)

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Liu, X., Wang, W., Wang, H. et al. A polypeptide from Chlamys farreri inhibits UVB-induced HaCaT cells apoptosis via the Apaf-1/caspase-9 and Smac/XIAP signaling pathway. Chin. J. Ocean. Limnol. 27, 587–593 (2009). https://doi.org/10.1007/s00343-009-9179-y

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