Transcriptional activation of gene expression by pluronic block copolymers in stably and transiently transfected cells

Srikanth Sriadibhatla, Zhihui Yang, Catherine Gebhart, Valery Yu Alakhov, Alexander Kabanov

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

Amphiphilic block copolymers of poly(ethylene oxide) and poly(propylene oxide) (Pluronics) enhance gene expression, but the mechanism remains unclear. We examined the effects of Pluronics on gene expression in murine cell models (NIH3T3 fibroblasts, C2C12 myoblasts, and Cl66 mammary adenocarcinoma cells) transfected with luciferase and green fluorescent protein. Addition of Pluronics to stably or transiently transfected cells enhanced transcription of the reporter genes. mRNA levels of the heat-shock protein hsp68 were also increased, whereas a housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase, was unaffected. Fibroblast and myoblast cells transfected with PathDetect cis-Reporting System constructs were used to examine the involvement of the nuclear factor-κB (NF-κB) and activating protein-1 (AP-1) in Pluronics enhancement. Pluronics enhanced reporter gene expression controlled by NF-κB in both cell models. They also increased expression of a gene under AP-1 in a fibroblast cell line, but not in a myoblast cell line. Activation of the inflammation signaling pathway in myoblast cells by Pluronics was shown by increased IκB phosphorylation. No cytotoxicity was observed at doses of Pluronics at which gene expression was increased. Overall, these results indicate that Pluronics can increase the transcription of genes, in part, through the activation of selected stress signaling pathways.

Original languageEnglish (US)
Pages (from-to)804-813
Number of pages10
JournalMolecular Therapy
Volume13
Issue number4
DOIs
StatePublished - Apr 2006

Keywords

  • Block copolymer
  • Gene delivery
  • NF-κB
  • Pluronic
  • Poloxamer
  • Transcription factor

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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