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): 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)
|