Effects of pergolide mesylate on transduction efficiency of PEP-1-catalase protein

Biochem Biophys Res Commun. 2011 Mar 18;406(3):336-40. doi: 10.1016/j.bbrc.2011.02.038. Epub 2011 Feb 13.

Abstract

The low transduction efficiency of various proteins is an obstacle to their therapeutic application. However, protein transduction domains (PTDs) are well-known for a highly effective tool for exogenous protein delivery to cells. We examined the effects of pergolide mesylate (PM) on the transduction of PEP-1-catalase into HaCaT human keratinocytes and mice skin and on the anti-inflammatory activity of PEP-1-catatase against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation using Western blot and histological analysis. PM enhanced the time- and dose-dependent transduction of PEP-1-catalase into HaCaT cells without affecting the cellular toxicity. In a mouse edema model, PEP-1-catalase inhibited the increased expressions of inflammatory mediators and cytokines such as cyclooxygenase-2, inducible nitric oxide synthase, interleukin-6 and -1β, and tumor necrosis factor-α induced by TPA. On the other hand, PM alone failed to exert any significant anti-inflammatory effects. However, the anti-inflammatory effect of co-treatment with PEP-1-catalase and PM was more potent than that of PEP-1-catalase alone. Our results indicate that PM may enhance the delivery of PTDs fusion therapeutic proteins to target cells and tissues and has potential to increase their therapeutic effects of such drugs against various diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / metabolism*
  • Catalase / administration & dosage
  • Catalase / metabolism*
  • Cell Line
  • Cysteamine / administration & dosage
  • Cysteamine / analogs & derivatives*
  • Cysteamine / metabolism
  • Dermatitis / drug therapy*
  • Drug Delivery Systems*
  • Humans
  • Keratinocytes / drug effects*
  • Keratinocytes / metabolism
  • Male
  • Mice
  • Mice, Inbred ICR
  • Peptides / administration & dosage
  • Peptides / metabolism*
  • Pergolide / pharmacology*
  • Protein Transport / drug effects
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / metabolism*
  • Tetradecanoylphorbol Acetate / analogs & derivatives
  • Tetradecanoylphorbol Acetate / toxicity

Substances

  • 12-O-tetradecanoylphorbol-1,3-acetate
  • Anti-Inflammatory Agents, Non-Steroidal
  • Pep-1 peptide
  • Peptides
  • Recombinant Fusion Proteins
  • Pergolide
  • Cysteamine
  • Catalase
  • PEP-1-catalase fusion protein
  • Tetradecanoylphorbol Acetate