Uncoupling oxidative phosphorylation with 2,4-dinitrophenol promotes development of the adhesion phenotype

Valerie I. Shavell, Nicole M. Fletcher, Zhong L. Jiang, Ghassan M. Saed, Michael P. Diamond

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Objective: To determine the effect of uncoupling oxidative phosphorylation with 2,4-dinitrophenol (DNP) on adhesion phenotype development. Design: Prospective experimental study. Setting: Academic medical center. Patient(s): Women undergoing laparotomy for pelvic pain from whom normal peritoneum and adhesions were excised to create primary cultures of normal peritoneal and adhesion fibroblasts. Intervention(s): Treatment of normal peritoneal and adhesion fibroblasts isolated from the same patient(s) with or without 0.2 mM DNP for 24 hours. Main Outcome Measure(s): Evaluation of adhesion phenotype markers type I collagen, vascular endothelial growth factor (VEGF), and hypoxia-inducible factor (HIF)-1α. Result(s): In agreement with prior findings, adhesion fibroblasts exhibited significantly higher basal levels of type I collagen, VEGF, and HIF-1α compared with normal peritoneal fibroblasts. Treatment of normal peritoneal fibroblasts with DNP resulted in significant increases in type I collagen (10.2 ± 1.4 vs. 18.4 ± 1.9 fg/μg RNA) and VEGF (8.2 ± 1.1 vs. 13.7 ± 0.4 fg/μg RNA) over baseline. HIF-1α levels did not increase when normal peritoneal fibroblasts were treated with DNP. Conclusion(s): The adhesion phenotype, which is normally expressed in response to hypoxia, is reproduced in a normoxic environment by uncoupling oxidative phosphorylation with DNP, as evidenced by an increase in type I collagen and VEGF. Acquisition of the adhesion phenotype was via a mechanism distinct from up-regulation of HIF-1α. These observations are consistent with the hypothesis that the adhesion phenotype represents a state of intracellular metabolic depletion.

Original languageEnglish (US)
Pages (from-to)729-733
Number of pages5
JournalFertility and sterility
Volume97
Issue number3
DOIs
StatePublished - Mar 1 2012
Externally publishedYes

Keywords

  • 2,4-dinitrophenol (DNP)
  • Postoperative adhesions
  • collagen
  • hypoxia-inducible factor (HIF)
  • oxidative phosphorylation
  • vascular endothelial growth factor (VEGF)

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

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