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 language | English (US) |
|---|---|
| Pages (from-to) | 729-733 |
| Number of pages | 5 |
| Journal | Fertility and Sterility |
| Volume | 97 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 1 2012 |
| Externally published | Yes |
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Keywords
- 2,4-dinitrophenol (DNP)
- collagen
- hypoxia-inducible factor (HIF)
- oxidative phosphorylation
- Postoperative adhesions
- vascular endothelial growth factor (VEGF)
ASJC Scopus subject areas
- Reproductive Medicine
- Obstetrics and Gynecology
Cite this
Uncoupling oxidative phosphorylation with 2,4-dinitrophenol promotes development of the adhesion phenotype. / Shavell, Valerie I.; Fletcher, Nicole M.; Jiang, Zhong L.; Saed, Ghassan M.; Diamond, Michael Peter.
In: Fertility and Sterility, Vol. 97, No. 3, 01.03.2012, p. 729-733.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Uncoupling oxidative phosphorylation with 2,4-dinitrophenol promotes development of the adhesion phenotype
AU - Shavell, Valerie I.
AU - Fletcher, Nicole M.
AU - Jiang, Zhong L.
AU - Saed, Ghassan M.
AU - Diamond, Michael Peter
PY - 2012/3/1
Y1 - 2012/3/1
N2 - 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.
AB - 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.
KW - 2,4-dinitrophenol (DNP)
KW - collagen
KW - hypoxia-inducible factor (HIF)
KW - oxidative phosphorylation
KW - Postoperative adhesions
KW - vascular endothelial growth factor (VEGF)
UR - http://www.scopus.com/inward/record.url?scp=84857784546&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84857784546&partnerID=8YFLogxK
U2 - 10.1016/j.fertnstert.2011.12.009
DO - 10.1016/j.fertnstert.2011.12.009
M3 - Article
VL - 97
SP - 729
EP - 733
JO - Fertility and Sterility
JF - Fertility and Sterility
SN - 0015-0282
IS - 3
ER -