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

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

Research output: Contribution to journalArticle

65 Citations (Scopus)

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 1 2006

Fingerprint

Poloxamer
Transcriptional Activation
Gene Expression
Myoblasts
Fibroblasts
Reporter Genes
Cell Line
Ethylene Oxide
Glyceraldehyde-3-Phosphate Dehydrogenases
Essential Genes
Heat-Shock Proteins
Green Fluorescent Proteins
Luciferases
Proteins
Adenocarcinoma
Breast
Phosphorylation
Inflammation
Messenger RNA

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Transcriptional activation of gene expression by pluronic block copolymers in stably and transiently transfected cells. / Sriadibhatla, Srikanth; Yang, Zhihui; Gebhart, Catherine L; Alakhov, Valery Yu; Kabanov, Alexander.

In: Molecular Therapy, Vol. 13, No. 4, 01.04.2006, p. 804-813.

Research output: Contribution to journalArticle

Sriadibhatla, Srikanth ; Yang, Zhihui ; Gebhart, Catherine L ; Alakhov, Valery Yu ; Kabanov, Alexander. / Transcriptional activation of gene expression by pluronic block copolymers in stably and transiently transfected cells. In: Molecular Therapy. 2006 ; Vol. 13, No. 4. pp. 804-813.
@article{77a0345eb3054d34a1967bba2d5597ed,
title = "Transcriptional activation of gene expression by pluronic block copolymers in stably and transiently transfected cells",
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.",
keywords = "Block copolymer, Gene delivery, NF-κB, Pluronic, Poloxamer, Transcription factor",
author = "Srikanth Sriadibhatla and Zhihui Yang and Gebhart, {Catherine L} and Alakhov, {Valery Yu} and Alexander Kabanov",
year = "2006",
month = "4",
day = "1",
doi = "10.1016/j.ymthe.2005.07.701",
language = "English (US)",
volume = "13",
pages = "804--813",
journal = "Molecular Therapy",
issn = "1525-0016",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - Transcriptional activation of gene expression by pluronic block copolymers in stably and transiently transfected cells

AU - Sriadibhatla, Srikanth

AU - Yang, Zhihui

AU - Gebhart, Catherine L

AU - Alakhov, Valery Yu

AU - Kabanov, Alexander

PY - 2006/4/1

Y1 - 2006/4/1

N2 - 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.

AB - 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.

KW - Block copolymer

KW - Gene delivery

KW - NF-κB

KW - Pluronic

KW - Poloxamer

KW - Transcription factor

UR - http://www.scopus.com/inward/record.url?scp=33645526489&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33645526489&partnerID=8YFLogxK

U2 - 10.1016/j.ymthe.2005.07.701

DO - 10.1016/j.ymthe.2005.07.701

M3 - Article

VL - 13

SP - 804

EP - 813

JO - Molecular Therapy

JF - Molecular Therapy

SN - 1525-0016

IS - 4

ER -