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

Hyongjun Jeon; Hee-Young Kim; Chang-Hwan Bae; Yukyung Lee; Sungtae Koo; Seungtae Kim

doi:10.1016/j.joim.2021.09.005

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

J Integr Med. 2021 Nov;19(6):537-544. doi: 10.1016/j.joim.2021.09.005. Epub 2021 Sep 14.

Authors

Hyongjun Jeon¹, Hee-Young Kim², Chang-Hwan Bae¹, Yukyung Lee¹, Sungtae Koo¹, Seungtae Kim³

Affiliations

¹ Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do 50612, Republic of Korea; Korean Medicine Research Center for Healthy Aging, Pusan National University, Yangsan, Gyeongsangnam-do 50612, Republic of Korea.
² Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do 50612, Republic of Korea.
³ Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do 50612, Republic of Korea; Korean Medicine Research Center for Healthy Aging, Pusan National University, Yangsan, Gyeongsangnam-do 50612, Republic of Korea. Electronic address: kimst@pusan.ac.kr.

PMID: 34580047
DOI: 10.1016/j.joim.2021.09.005

Abstract

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.

Keywords: 1-Methyl-4-phenylpyridinium; Apoptosis; Korean red ginseng; Mitophagy; Parkinson’s disease.

MeSH terms

1-Methyl-4-phenylpyridinium* / toxicity
Apoptosis
Cell Line, Tumor
Humans
Mitochondria
Mitophagy*
Panax* / chemistry
Reactive Oxygen Species

Substances

Reactive Oxygen Species
1-Methyl-4-phenylpyridinium