Green fluorescent protein selectively induces HSP70-mediated up-regulation of COX-2 expression in endothelial cells. Academic Article uri icon

Overview

MeSH

  • Adenoviridae
  • Animals
  • Cells, Cultured
  • Cyclooxygenase 2
  • Dinoprostone
  • Ear, External
  • Gene Expression Regulation, Enzymologic
  • Genetic Vectors
  • Green Fluorescent Proteins
  • Humans
  • MAP Kinase Signaling System
  • Membrane Proteins
  • Mice
  • Muscle, Smooth, Vascular
  • Phosphatidylinositol 3-Kinases
  • Transcription, Genetic
  • Umbilical Veins
  • Up-Regulation
  • Vasodilation

MeSH Major

  • Endothelium, Vascular
  • HSP70 Heat-Shock Proteins
  • Indicators and Reagents
  • Isoenzymes
  • Luminescent Proteins
  • Prostaglandin-Endoperoxide Synthases

abstract

  • Reporter genes, including green fluorescent protein (GFP), have been used to monitor the expression of transgenes introduced into vascular cells by gene transfer vectors. Here, we demonstrate that GFP by itself can selectively induce expression of certain genes in endothelial cells. Elevation of the cytoplasmic concentration of GFP in endothelial cells, specifically, resulted in a robust upregulation of heat shock protein 70 (HSP70). GFP induced both mRNA and protein expression of HSP70 in a dose-dependent manner. GFP-mediated up-regulation of HSP70 resulted in induction of cyclooxygenase-2 (COX-2) followed by prostaglandin E2 (PGE2) production. GFP-mediated up-regulation of HSP70 is independent of mitogen-activated protein kinase and phosphatidylinositol-3-kinase signaling cascades because inhibition of these pathways had no effect on HSP70 increases. Adenoviral delivery of GFP into murine vasculature significantly enhanced blood flow, suggesting that sufficient PGE2 is produced to induce vasodilation. Identification of the molecular partners that interact with GFP will increase our understanding of the vascular-specific factors that regulate stress angiogenesis and hemostasis.

publication date

  • September 15, 2003

has subject area

  • Adenoviridae
  • Animals
  • Cells, Cultured
  • Cyclooxygenase 2
  • Dinoprostone
  • Ear, External
  • Endothelium, Vascular
  • Gene Expression Regulation, Enzymologic
  • Genetic Vectors
  • Green Fluorescent Proteins
  • HSP70 Heat-Shock Proteins
  • Humans
  • Indicators and Reagents
  • Isoenzymes
  • Luminescent Proteins
  • MAP Kinase Signaling System
  • Membrane Proteins
  • Mice
  • Muscle, Smooth, Vascular
  • Phosphatidylinositol 3-Kinases
  • Prostaglandin-Endoperoxide Synthases
  • Transcription, Genetic
  • Umbilical Veins
  • Up-Regulation
  • Vasodilation

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1182/blood-2003-01-0049

PubMed ID

  • 12805066

Additional Document Info

start page

  • 2115

end page

  • 2121

volume

  • 102

number

  • 6