Adhesion phenotype manifests an altered metabolic profile favoring glycolysis

Nicole M. Fletcher, Awoniyi O. Awonuga, Mohammed S. Abusamaan, Mohammed G. Saed, Michael P. Diamond, Ghassan M. Saed

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Objective To determine whether metabolic markers are differentially expressed in normal and adhesion fibroblasts with and without hypoxia exposure. Design Prospective experimental study. Setting University research laboratory. Patient(s) Fibroblasts established from normal peritoneum and adhesion tissues from the same patients. Intervention(s) In vitro experiments on normal peritoneal and adhesion fibroblasts under normal and hypoxic (2% O2) conditions. Main Outcome Measure(s) Expression of metabolic markers, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), glucose transporter 1 (GLUT1), hypoxia inducible factor (HIF)-1α, hexokinase 2 (HK2), lactose dehydrogenase A (LDHA), and pyruvate dehydrogenase alpha 1 (PDHA1) were measured using real-time reverse transcription polymerase chain reaction; adenosine triphosphate (ATP), HIF-1α, and lactate levels were assessed with ELISAs. Result(s) Baseline mRNA levels of GAPDH and HIF-1α were increased, while GLUT1 and PDHA1 were decreased in adhesion as compared with in normal peritoneal fibroblasts. There was no change in baseline levels of HK2 or LDHA between the cell lines. Hypoxia increased protein levels of HIF-1α and mRNA levels of GAPDH, GLUT1, and HK2 and decreased levels of PDHA1 in both cell lines. Hypoxia increased LDHA mRNA levels in normal peritoneal fibroblasts. Baseline levels of lactate and ATP were lower in adhesion as compared with in normal peritoneal fibroblasts. In response to hypoxia, there was an increase in lactate in both cell lines and a decrease in ATP in normal fibroblasts. Conclusion(s) Adhesion fibroblasts manifested an altered metabolic profile, which favors the glycolytic pathway, and is further altered by hypoxia. Targeting these specific metabolic markers during surgery can be an important therapeutic intervention minimizing the development of postoperative adhesions.

Original languageEnglish (US)
Pages (from-to)1628-1637.e1
JournalFertility and sterility
Volume105
Issue number6
DOIs
StatePublished - Jun 1 2016

Fingerprint

Metabolome
Glycolysis
Fibroblasts
Phenotype
Hypoxia-Inducible Factor 1
Oxidoreductases
Glyceraldehyde-3-Phosphate Dehydrogenases
Hexokinase
Facilitative Glucose Transport Proteins
Lactose
Pyruvic Acid
Lactic Acid
Adenosine Triphosphate
Cell Line
Messenger RNA
Tissue Adhesions
Peritoneum
Reverse Transcription
Research Design
Enzyme-Linked Immunosorbent Assay

Keywords

  • Postoperative adhesions
  • adhesion phenotype
  • glycolysis
  • hypoxia
  • metabolic markers

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

Cite this

Fletcher, N. M., Awonuga, A. O., Abusamaan, M. S., Saed, M. G., Diamond, M. P., & Saed, G. M. (2016). Adhesion phenotype manifests an altered metabolic profile favoring glycolysis. Fertility and sterility, 105(6), 1628-1637.e1. https://doi.org/10.1016/j.fertnstert.2016.02.009

Adhesion phenotype manifests an altered metabolic profile favoring glycolysis. / Fletcher, Nicole M.; Awonuga, Awoniyi O.; Abusamaan, Mohammed S.; Saed, Mohammed G.; Diamond, Michael P.; Saed, Ghassan M.

In: Fertility and sterility, Vol. 105, No. 6, 01.06.2016, p. 1628-1637.e1.

Research output: Contribution to journalArticle

Fletcher, NM, Awonuga, AO, Abusamaan, MS, Saed, MG, Diamond, MP & Saed, GM 2016, 'Adhesion phenotype manifests an altered metabolic profile favoring glycolysis', Fertility and sterility, vol. 105, no. 6, pp. 1628-1637.e1. https://doi.org/10.1016/j.fertnstert.2016.02.009
Fletcher, Nicole M. ; Awonuga, Awoniyi O. ; Abusamaan, Mohammed S. ; Saed, Mohammed G. ; Diamond, Michael P. ; Saed, Ghassan M. / Adhesion phenotype manifests an altered metabolic profile favoring glycolysis. In: Fertility and sterility. 2016 ; Vol. 105, No. 6. pp. 1628-1637.e1.
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AU - Diamond, Michael P.

AU - Saed, Ghassan M.

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AB - Objective To determine whether metabolic markers are differentially expressed in normal and adhesion fibroblasts with and without hypoxia exposure. Design Prospective experimental study. Setting University research laboratory. Patient(s) Fibroblasts established from normal peritoneum and adhesion tissues from the same patients. Intervention(s) In vitro experiments on normal peritoneal and adhesion fibroblasts under normal and hypoxic (2% O2) conditions. Main Outcome Measure(s) Expression of metabolic markers, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), glucose transporter 1 (GLUT1), hypoxia inducible factor (HIF)-1α, hexokinase 2 (HK2), lactose dehydrogenase A (LDHA), and pyruvate dehydrogenase alpha 1 (PDHA1) were measured using real-time reverse transcription polymerase chain reaction; adenosine triphosphate (ATP), HIF-1α, and lactate levels were assessed with ELISAs. Result(s) Baseline mRNA levels of GAPDH and HIF-1α were increased, while GLUT1 and PDHA1 were decreased in adhesion as compared with in normal peritoneal fibroblasts. There was no change in baseline levels of HK2 or LDHA between the cell lines. Hypoxia increased protein levels of HIF-1α and mRNA levels of GAPDH, GLUT1, and HK2 and decreased levels of PDHA1 in both cell lines. Hypoxia increased LDHA mRNA levels in normal peritoneal fibroblasts. Baseline levels of lactate and ATP were lower in adhesion as compared with in normal peritoneal fibroblasts. In response to hypoxia, there was an increase in lactate in both cell lines and a decrease in ATP in normal fibroblasts. Conclusion(s) Adhesion fibroblasts manifested an altered metabolic profile, which favors the glycolytic pathway, and is further altered by hypoxia. Targeting these specific metabolic markers during surgery can be an important therapeutic intervention minimizing the development of postoperative adhesions.

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