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Levosulpiride, (S)-(-)-5-Aminosulfonyl-N-[(1-ethyl-2-pyrrolidinyl) methyl]-2-methoxybenzamide, enhances the transduction efficiency of PEP-1-ribosomal protein S3 in vitro and in vivo

  • Ahn, Eun-Hee (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Kim, Dae-Won (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Kim, Duk-Soo (Department of Anatomy, College of Medicine, Soonchunhyang University) ;
  • Woo, Su-Jung (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Kim, Hye-Ri (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Kim, Joon (School of Life Science and Biotechnology, Korea University) ;
  • Lim, Soon-Sung (Department of Food Science and Nutrition & RIC Center, Hallym University) ;
  • Kang, Tae-Cheon (Department of Anatomy and Neurobiology, College of Medicine, Hallym University) ;
  • Kim, Dong-Joon (Department of Internal Medicine, Chuncheon Sacred Heart Hospital, Hallym University) ;
  • Suk, Ki-Tae (Department of Internal Medicine, Chuncheon Sacred Heart Hospital, Hallym University) ;
  • Park, Jin-Seu (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Luo, Qiuxiang (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Eum, Won-Sik (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Hwang, Hyun-Sook (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Choi, Soo-Young (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University)
  • Received : 2011.02.07
  • Accepted : 2011.03.03
  • Published : 2011.05.31

Abstract

Many proteins with poor transduction efficiency were reported to be delivered to cells by fusion with protein transduction domains (PTDs). In this study, we investigated the effect of levosulpiride on the transduction of PEP-1 ribosomal protein S3 (PEP-1-rpS3), and examined its influence on the stimulation of the therapeutic properties of PEP-1-rpS3. PEP-1-rpS3 transduction into HaCaT human keratinocytes and mouse skin was stimulated by levosulpiride in a manner that did not directly affect the cell viability. Following 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice, levosulpiride alone was ineffective in reducing TPA-induced edema and in inhibiting the elevated productions of inflammatory mediators and cytokines, such as cyclooxygenase-2, inducible nitric oxide synthase, interleukin-6 and -1${\beta}$, and tumor necrosis factor-${\alpha}$. Anti-inflammatory activity by PEP-1-rpS3 + levosulpiride was significantly more potent than by PEP-1-rpS3 alone. These results suggest that levosulpiride may be useful for enhancing the therapeutic effect of PEP-1-rpS3 against various inflammatory diseases.

Keywords

Inflammation;Levosulpiride;PEP-1-rpS3;Protein therapy;Protein transduction

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