Shifting anaerobic to aerobic metabolism stimulates apoptosis through modulation of redox balance: Potential intervention in the pathogenesis of postoperative adhesions

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

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Objective To compare the effect of shifting anaerobic to aerobic metabolism on key regulators of oxidative stress, including extracellular superoxide dismutase (SOD3), inducible nitric oxide synthase (iNOS), and its product, nitric oxide (NO), as well as mitochondrial potential (Δψm) and apoptosis in fibroblasts established from normal peritoneum and adhesion tissues. Design Prospective, experimental study. Setting University medical center. Patient(s) Fibroblasts established from normal peritoneum and adhesion tissues from the same patients. Intervention(s) Treatment with dichloroacetate (0, 20, 40, and 80 μg/mL, 24 hours). Main Outcome Measure(s) The expression of SOD3, iNOS, and NO levels were measured utilizing real-time reverse transcription-polymerase chain reaction and Greiss assay. The Δψm was evaluated by the JC-1 Mitochondrial Membrane Potential Assay. Apoptosis was determined by caspase-3 activity and TUNEL assays. Data were analyzed using SPSS 19.0. Mixed model repeated-measures analysis of variance was used with a Bonferroni correction. Significant interactions were analyzed with independent sample t tests. Result(s) Dichloroacetate increased apoptosis, SOD3 messenger RNA, iNOS messenger RNA, and NO levels in fibroblasts from peritoneum and adhesions. There was enhanced Δψm adhesion as compared with normal peritoneal fibroblasts. Creating oxidative stress by exposure by hypoxia markedly increased Δψm in fibroblasts from normal peritoneum to levels observed in adhesions; dichloroacetate protected against the effects of hypoxia. Conclusion(s) Anaerobic metabolism and oxidative stress are associated with the development of the adhesion phenotype, which manifests decreased apoptosis. Dichloroacetate induces adhesion fibroblasts to undergo apoptosis via modulation of redox homeostasis. These findings may provide targets for therapeutic treatment for reduction of profibrotic disorders, including postoperative adhesions.

Original languageEnglish (US)
Pages (from-to)1022-1029
Number of pages8
JournalFertility and sterility
Volume104
Issue number4
DOIs
StatePublished - Oct 1 2015

Keywords

  • Dichloroacetate
  • apoptosis
  • oxidative stress
  • postoperative adhesions

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

Fingerprint Dive into the research topics of 'Shifting anaerobic to aerobic metabolism stimulates apoptosis through modulation of redox balance: Potential intervention in the pathogenesis of postoperative adhesions'. Together they form a unique fingerprint.

  • Cite this