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Journal of Integrative Medicine ›› 2021, Vol. 19 ›› Issue (6): 537-544.doi: 10.1016/j.joim.2021.09.005

• Original Experimental Research • Previous Articles     Next Articles

Korean red ginseng decreases 1-methyl-4-phenylpyridinium-induced mitophagy in SH-SY5Y cells

Hyongjun Jeona,b, Hee-Young Kima, Chang-Hwan Baea,b, Yukyung Leea,b, Sungtae Kooa,b, Seungtae Kima,b   

  1. a. Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do 50612, Republic of Korea
    b. Korean Medicine Research Center for Healthy Aging, Pusan National University, Yangsan, Gyeongsangnam-do 50612, Republic of Korea
  • Online:2021-11-12 Published:2021-11-12
  • Contact: Seungtae Kim kimst@pusan.ac.kr E-mail:kimst@pusan.ac.kr

Objective

Mitophagy is known to contribute towards progression of Parkinson’s disease. Korean red ginseng (KRG) is a widely used medicinal herb in East Asia, and recent studies have reported that KRG prevents 1-methyl-4-phenylpyridinium ion (MPP+)-induced cell death. This study was undertaken to investigate whether KRG suppresses MPP+-induced apoptosis and mitophagy.

Methods

SH-SY5Y cells were incubated with KRG for 24 h, and subsequently exposed to MPP+. The MPP+-induced cell death was confirmed with the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay. Changes in the structure and function of mitochondria were confirmed using mitotracker, MitoSOX red mitochondrial superoxide indicator, parkin, and phosphatase and tensin homolog deleted on chromosome ten-induced putative kinase 1 (PINK1) immunofluorescent staining. Western blotting was performed to evaluate the expression of apoptosis-related factors in whole cells, including Bax, Bcl-2 and cleaved caspase-3, and mitophagy-related factors in the mitochondrial fraction, including cytochrome c, parkin, PINK1, translocase of the outer membrane 20 (TOM20), p62 and Beclin 1.

Results

MPP+ induced cell death by cytochrome c release and caspase-3 activation; however this effect was suppressed by KRG’s regulation of the expressions of Bcl-2 and Bax. Moreover, MPP+ exposure increased the mitochondrial expressions of parkin, PINK1, Beclin 1 and p62, and decreased TOM20, cytochrome c and Bcl-2 expressions. These MPP+-induced changes in the mitochondrial fraction were attenuated by treatment with KRG.

Conclusion

KRG effectively prevents MPP+-induced SH-SY5Y cell death by regulating cytochrome c release from mitochondria and PINK1/parkin-mediated mitophagy, through regulation of the Bcl-2 family.

Key words: Parkinson’s disease, Apoptosis, Mitophagy, 1-Methyl-4-phenylpyridinium, Korean red ginseng

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