The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Gallic acid-mitochondria targeting sequence-H3R9 induces mitochondria-targeted cytoprotection

  • Bae, Yoonhee (Department of Physiology, Cardiovascular and Metabolic Disease Center, Smart Marine Therapeutic Center, Inje University College of Medicine) ;
  • Kim, Goo-Young (Department of Biology and Clinical Pharmacology, R&D Center, Samyang Biopharmaceuticals Corporation) ;
  • Jessa, Flores (Department of Physiology, Cardiovascular and Metabolic Disease Center, Smart Marine Therapeutic Center, Inje University College of Medicine) ;
  • Ko, Kyung Soo (Department of Physiology, Cardiovascular and Metabolic Disease Center, Smart Marine Therapeutic Center, Inje University College of Medicine) ;
  • Han, Jin (Department of Physiology, Cardiovascular and Metabolic Disease Center, Smart Marine Therapeutic Center, Inje University College of Medicine)
  • Received : 2021.04.01
  • Accepted : 2021.10.21
  • Published : 2022.01.01
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Abstract

The development of selective targeting of drug molecules towards the mitochondria is an important issue related to therapy efficacy. In this study, we report that gallic acid (GA)-mitochondria targeting sequence (MTS)-H3R9 exhibits a dual role as a mitochondria-targeting vehicle with antioxidant activity for disease therapy. In viability assays, GA-MTS-H3R9 showed a better rescue action compared to that of MTS-H3R9. GA-MTS-H3R9 dramatically exhibited cell penetration and intercellular uptake compared to MTS and fit escape from lysosome release to the cytosol. We demonstrated the useful targeting of GA-MTS-H3R9 towards mitochondria in AC16 cells. Also, we observed that the antioxidant properties of mitochondrial-accrued GA-MTS-H3R9 alleviated cell damage by reactive oxygen species production and disrupted mitochondrial membrane potential. GA-MTS-H3R9 showed a very increased cytoprotective effect against anticancer activity compared to that of MTS-H3R9. We showed that GA-MTS-H3R9 can act as a vehicle for mitochondria-targeting and as a reagent for therapeutic applications intended for cardiovascular disease treatment.

Keywords

Acknowledgement

This research was supported by the Basic Research Lab Program (2020R1A4A1018943) and the Basic Science Research Program (2018R1A2A3074998, 2019R1I1A1A01061429) through the National Research Foundation of Korea funded by the Ministry of Science and ICT, Korea.

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