Oxidative stress

a key regulator of leiomyoma cell survival

Nicole M. Fletcher, Mohammed S. Abusamaan, Ira Memaj, Mohammed G. Saed, Ayman Al-Hendy, Michael Peter Diamond, Ghassan M. Saed

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Objective To determine the effects of attenuating oxidative stress with the use of dichloroacetate (DCA) on the expression of key redox enzymes myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) as well as on apoptosis. Design Prospective experimental study. Setting University medical center. Patient(s) Cells established from myometrium and uterine fibroid from the same patients. Intervention(s) Cells were exposed to normal (20% O2) or hypoxic (2% O2) conditions for 24 hours with or without DCA (20 μg/mL), a metabolic modulator that shifts anaerobic to aerobic metabolism. Main Outcome Measure(s) Nitrate/nitrite (iNOS activity indicator), iNOS, Bcl-2/Bax ratio, MPO, and caspase-3 activities and levels were determined by means of Greiss assay, real-time reverse-transcription polymerase chain reaction, and ELISA. Data were analyzed with the use of SPSS by means of one-way analysis of variance with Tukey post hoc analysis and independent t tests. Result(s) MPO, iNOS, and nitrate/nitrite expression were higher in leiomyoma than in myometrial cells, and they were further enhanced by hypoxia in myometrial cells. Treatment with the use of DCA decreased MPO, iNOS, and nitrate/nitrite levels and negated the effect of hypoxia in both types of cells. Leiomyoma cells showed less apoptosis, as indicated by both caspase-3 activity and the Bcl-2/Bax ratio, than myometrial cells. Hypoxia further decreased apoptosis in myometrial cells with no further effect on leiomyoma cells. Treatment with DCA resulted in increased apoptosis in both types of cells, even in the presence of hypoxia. Conclusion(s) Shifting anaerobic to aerobic metabolism with the use of DCA resulted in an increase in apoptosis in leiomyoma cells and protected myometrial cells from the acquisition of the leiomyoma-like phenotype.

Original languageEnglish (US)
Pages (from-to)1387-1394.e1
JournalFertility and sterility
Volume107
Issue number6
DOIs
StatePublished - Jun 1 2017

Fingerprint

Leiomyoma
Cell Survival
Oxidative Stress
Nitric Oxide Synthase Type II
Peroxidase
Apoptosis
Nitrites
Nitrates
Caspase 3
Myometrium
Reverse Transcription
Oxidation-Reduction
Analysis of Variance
Research Design
Enzyme-Linked Immunosorbent Assay
Outcome Assessment (Health Care)
Prospective Studies
Phenotype

Keywords

  • Dichloroacetate
  • apoptosis
  • leiomyoma
  • myometrium
  • oxidative stress

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

Cite this

Fletcher, N. M., Abusamaan, M. S., Memaj, I., Saed, M. G., Al-Hendy, A., Diamond, M. P., & Saed, G. M. (2017). Oxidative stress: a key regulator of leiomyoma cell survival. Fertility and sterility, 107(6), 1387-1394.e1. https://doi.org/10.1016/j.fertnstert.2017.04.015

Oxidative stress : a key regulator of leiomyoma cell survival. / Fletcher, Nicole M.; Abusamaan, Mohammed S.; Memaj, Ira; Saed, Mohammed G.; Al-Hendy, Ayman; Diamond, Michael Peter; Saed, Ghassan M.

In: Fertility and sterility, Vol. 107, No. 6, 01.06.2017, p. 1387-1394.e1.

Research output: Contribution to journalArticle

Fletcher, NM, Abusamaan, MS, Memaj, I, Saed, MG, Al-Hendy, A, Diamond, MP & Saed, GM 2017, 'Oxidative stress: a key regulator of leiomyoma cell survival', Fertility and sterility, vol. 107, no. 6, pp. 1387-1394.e1. https://doi.org/10.1016/j.fertnstert.2017.04.015
Fletcher NM, Abusamaan MS, Memaj I, Saed MG, Al-Hendy A, Diamond MP et al. Oxidative stress: a key regulator of leiomyoma cell survival. Fertility and sterility. 2017 Jun 1;107(6):1387-1394.e1. https://doi.org/10.1016/j.fertnstert.2017.04.015
Fletcher, Nicole M. ; Abusamaan, Mohammed S. ; Memaj, Ira ; Saed, Mohammed G. ; Al-Hendy, Ayman ; Diamond, Michael Peter ; Saed, Ghassan M. / Oxidative stress : a key regulator of leiomyoma cell survival. In: Fertility and sterility. 2017 ; Vol. 107, No. 6. pp. 1387-1394.e1.
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abstract = "Objective To determine the effects of attenuating oxidative stress with the use of dichloroacetate (DCA) on the expression of key redox enzymes myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) as well as on apoptosis. Design Prospective experimental study. Setting University medical center. Patient(s) Cells established from myometrium and uterine fibroid from the same patients. Intervention(s) Cells were exposed to normal (20{\%} O2) or hypoxic (2{\%} O2) conditions for 24 hours with or without DCA (20 μg/mL), a metabolic modulator that shifts anaerobic to aerobic metabolism. Main Outcome Measure(s) Nitrate/nitrite (iNOS activity indicator), iNOS, Bcl-2/Bax ratio, MPO, and caspase-3 activities and levels were determined by means of Greiss assay, real-time reverse-transcription polymerase chain reaction, and ELISA. Data were analyzed with the use of SPSS by means of one-way analysis of variance with Tukey post hoc analysis and independent t tests. Result(s) MPO, iNOS, and nitrate/nitrite expression were higher in leiomyoma than in myometrial cells, and they were further enhanced by hypoxia in myometrial cells. Treatment with the use of DCA decreased MPO, iNOS, and nitrate/nitrite levels and negated the effect of hypoxia in both types of cells. Leiomyoma cells showed less apoptosis, as indicated by both caspase-3 activity and the Bcl-2/Bax ratio, than myometrial cells. Hypoxia further decreased apoptosis in myometrial cells with no further effect on leiomyoma cells. Treatment with DCA resulted in increased apoptosis in both types of cells, even in the presence of hypoxia. Conclusion(s) Shifting anaerobic to aerobic metabolism with the use of DCA resulted in an increase in apoptosis in leiomyoma cells and protected myometrial cells from the acquisition of the leiomyoma-like phenotype.",
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AU - Memaj, Ira

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AU - Al-Hendy, Ayman

AU - Diamond, Michael Peter

AU - Saed, Ghassan M.

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KW - myometrium

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