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

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.

• Authors: Valerie I Shavell, Nicole M Fletcher, Zhong L Jiang, Ghassan M Saed, Michael P Diamond
• Journal: Fertility and sterility (Fertil Steril) Vol. 97 Issue 3 Pg. 729-33 (Mar 2012) ISSN: 1556-5653 [Electronic] United States
• PMID: 22200174 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Chemical References

• Collagen Type I
• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• RNA, Messenger
• Uncoupling Agents
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• 2,4-Dinitrophenol

Topics

• 2,4-Dinitrophenol (pharmacology)
• Cells, Cultured
• Collagen Type I (genetics, metabolism)
• Female
• Fibroblasts (drug effects, metabolism, pathology)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (genetics, metabolism)
• Mitochondria (drug effects, metabolism)
• Oxidative Phosphorylation (drug effects)
• Pelvic Pain (metabolism, pathology, surgery)
• Phenotype
• RNA, Messenger (metabolism)
• Tissue Adhesions
• Uncoupling Agents (pharmacology)
• Up-Regulation
• Vascular Endothelial Growth Factor A (genetics, metabolism)