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Modulation of ARTS and XIAP by Parkin Is Associated with Carnosic Acid Protects SH-SY5Y Cells against 6-Hydroxydopamine-Induced Apoptosis

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Abstract

The mediation of apoptosis-related protein in the TGF-β signaling pathway (ARTS) and X-liked inhibitor of apoptosis protein (XIAP) by parkin plays a critical role in preventing Parkinson’s disease. We studied whether carnosic acid (CA) could prevent 6-hydroxydopamine (6-OHDA)-induced apoptosis by modulating ARTS and XIAP through parkin in SH-SY5Y cells. In cells treated with 6-OHDA, the protein expression of ARTS is increased and XIAP is decreased. Pretreatment of cells with CA reversed these effects. Moreover, CA attenuated the activation of caspase 9 and caspase 7 by 6-OHDA. By immunoprecipitation with ARTS antibody, we found that 6-OHDA increased the protein expression of XIAP. However, pretreatment of cells with CA reduced XIAP protein and increased the ubiquitination of ARTS. Silencing of parkin attenuated the ability of CA to reverse the induction of ARTS and apoptotic-related proteins and the reduction of XIAP and parkin protein by 6-OHDA. Similarly, reversal of 6-OHDA-induced nuclear condensation and apoptotic-related proteins by CA was inhibited in cells with XIAP silencing. In conclusion, CA induces parkin by enhancing the ubiquitination of ARTS, leading to induction of XIAP. This may be a novel strategy for preventing Parkinson’s disease.

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Abbreviations

ARTS:

Apoptosis-related protein in the TGF-β signaling pathway

BIR:

Baculoviral IAP repeat

CA:

Carnosic acid

DMSO:

Dimethyl sulfoxide

IAP:

Inhibitor of apoptosis family of proteins

6-OHDA:

6-Hydroxydopamine

MPTP:

Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

PARP:

Poly-ADP ribose polymerase

PD:

Parkinson’s disease

siRNA:

Small-interfering RNA

UPS:

Ubiquitin-proteasome system

XIAP:

X-liked inhibitor of apoptosis protein.

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Acknowledgements

This work was supported by the Ministry of Science and Technology (MOST 103-2320-B-039-042-MY3).

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Authors and Affiliations

  1. Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

    Ru-Huei Fu

  2. Translational Medicine Research Center, China Medical University Hospital, Taichung, Taiwan

    Ru-Huei Fu

  3. Department of Nutrition, China Medical University, Taichung, Taiwan

    Li-Chun Huang, Chia-Yuan Lin & Chia-Wen Tsai

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Fu, RH., Huang, LC., Lin, CY. et al. Modulation of ARTS and XIAP by Parkin Is Associated with Carnosic Acid Protects SH-SY5Y Cells against 6-Hydroxydopamine-Induced Apoptosis. Mol Neurobiol 55, 1786–1794 (2018). https://doi.org/10.1007/s12035-017-0443-4

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