Oxytocin depolarizes mitochondria in isolated myometrial cells

Gravina, Fernanda Sbaraini; Jobling, Phillip; Kerr, Karen; Oliveira, Ramatis Birnfeld de; Parkington, Helena C.; Helden, Dirk F. van

doi:10.1113/expphysiol.2011.058388

Cited by 14 publications

(11 citation statements)

References 29 publications

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“…Apparently this parameter is more sensitive to oxytocin-effect induced by 10 nM was not exceeded by higher doses. Stimulating effect of oxytocin on mitochondrial activity is in keeping with other studies demonstrating depolarizing effect of oxytocin on mitochondria in isolated myometrial cells (Gravina et al 2011) and results of Alizadeh et al (2010) which found cardioprotective effects of oxytocin mediated by mitochondrial ATP-dependent potassium channels. No protective effect of oxytocin was observed in a peroxide model of oxidative stress.…”

Section: Discussionsupporting

confidence: 54%

Effect of Oxytocin on Neuroblastoma Cell Viability and Growth

et al. 2012

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Oxytocin, released in response to different physiological stimuli, could play a key role in reducing stress reaction. It was suggested that it has protective effect against inflammation and consequences of oxidative stress. Mechanisms how oxytocin effects mediated in the brain tissue are unclear. In this study, oxytocin effect on cell growth and neuronal viability was examined. Human neuroblastoma (SH-SY5Y and SK-N-SH) and glioblastoma (U87MG) cells were exposed to different concentrations of oxytocin for 12-96 h. Potential protective effect of oxytocin treatment was investigated after exposing cells to oxidative stress using hydrogen peroxide (50 mM, 2 h) or 6-hydroxydopamine (25 μM, 24 h). Cell proliferation was measured by cell counting and cell viability was examined by MTT assay. Protein expression of selected neurotrophic factors was measured as an additional parameter. Oxytocin (1 μM) significantly increased cell number in all three cell types. Viability of SH-SY5Y cells was increased in the presence of oxytocin without significant effect of dose (0.01-1 μM). Cell death induced by hydrogen peroxide was not prevented by incubation with oxytocin. Oxytocin pretreatment blunted neurotoxin 6-OHDA reduction of cell viability in SH-SY5Y cells. Oxytocin (1 μM, 12 h) elevated amount of total proteins without increasing levels of brain-derived neurotrophic factor and neurotrophic growth factor. In conclusion, oxytocin increases growth and viability of neuroblastoma and glioblastoma cells without activation of neurotrophic factors. Oxytocin does not have protective effect in oxidative stress; however, it might be important for neuroprotection to dopaminergic neurons. Its proliferative effect might be important in native cell life, euplastic processes, and tumor progression.

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Section: Discussionsupporting

confidence: 54%

Effect of Oxytocin on Neuroblastoma Cell Viability and Growth

et al. 2012

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“…Other, yet unidentified, physiological and pathological factors likely will be found to directly or indirectly activate or block the activity of the mitoK ATP channel. Mitochondria depolarize under normal conditions (121) and naturally occurring substances, such as oxytocin depolarize mitochondria in myometrial cells by either direct or indirect mechanisms (68).…”

Section: Mitochondrial Depolarization and Related Signaling Eventsmentioning

confidence: 99%

Role of Mitochondria in Cerebral Vascular Function: Energy Production, Cellular Protection, and Regulation of Vascular Tone

Busija

Rutkai

Dutta

et al. 2016

Comprehensive Physiology

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Mitochondria not only produce energy in the form of ATP to support the activities of cells comprising the neurovascular unit, but mitochondrial events, such as depolarization and/or ROS release, also initiate signaling events which protect the endothelium and neurons against lethal stresses via pre-/postconditioning as well as promote changes in cerebral vascular tone. Mitochondrial depolarization in vascular smooth muscle (VSM), via pharmacological activation of the ATP-dependent potassium channels on the inner mitochondrial membrane (mitoKATP channels), leads to vasorelaxation through generation of calcium sparks by the sarcoplasmic reticulum and subsequent downstream signaling mechanisms. Increased release of ROS by mitochondria has similar effects. Relaxation of VSM can also be indirectly achieved via actions of nitric oxide (NO) and other vasoactive agents produced by endothelium, perivascular and parenchymal nerves, and astroglia following mitochondrial activation. Additionally, NO production following mitochondrial activation is involved in neuronal preconditioning. Cerebral arteries from female rats have greater mitochondrial mass and respiration and enhanced cerebral arterial dilation to mitochondrial activators. Preexisting chronic conditions such as insulin resistance and/or diabetes impair mitoKATP channel relaxation of cerebral arteries and preconditioning. Surprisingly, mitoKATP channel function after transient ischemia appears to be retained in the endothelium of large cerebral arteries despite generalized cerebral vascular dysfunction. Thus, mitochondrial mechanisms may represent the elusive signaling link between metabolic rate and blood flow as well as mediators of vascular change according to physiological status. Mitochondrial mechanisms are an important, but underutilized target for improving vascular function and decreasing brain injury in stroke patients. © 2016 American Physiological Society. Compr Physiol 6:1529-1548, 2016.

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“…; Gravina et al . ). This could comprise an alternative explanation (given the reduction in mtDNA copy number) for our observations showing that myometrium from older pregnant mice has altered contractility in vitro .…”

Section: Discussionmentioning

confidence: 97%

Effect of reproductive ageing on pregnant mouse uterus and cervix

Patel

Moffatt

Mourmoura

et al. 2017

The Journal of Physiology

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Key points Older pregnant women have a greater risk of operative delivery, still birth and post‐term induction.This suggests that maternal age can influence the timing of birth and processes of parturition.We have found that increasing maternal age in C57BL/6J mice is associated with prolongation of gestation and length of labour.Older pregnant mice also had delayed progesterone withdrawal and impaired myometrial function.Uterine ageing and labour dysfunction should be investigated further in older primigravid women. AbstractAdvanced maternal age (≥35 years) is associated with increased rates of operative delivery, stillbirth and post‐term labour induction. The physiological causes remain uncertain, although impaired myometrial function has been implicated. To investigate the hypothesis that maternal age directly influences successful parturition, we assessed the timing of birth and fetal outcome in pregnant C57BL/6J mice at 3 months (young) and 5 months (intermediate) vs. 8 months (older) of age using infrared video recording. Serum progesterone profiles, myometrium and cervix function, and mitochondrial electron transport chain complex enzymatic activities were also examined. Older pregnant mice had a longer mean gestation and labour duration (P < 0.001), as well as reduced litter size (P < 0.01) vs. 3‐month‐old mice. Older mice did not exhibit the same decline in serum progesterone concentrations as younger mice. Cervical tissues from older mice were more distensible than younger mice (P < 0.05). Oxytocin receptor and connexin‐43 mRNA expression were reduced in the myometrium from 8‐month‐old vs. 3‐month‐old mice (P < 0.05 and P < 0.01 respectively) in tandem with more frequent but shorter duration spontaneous myometrial contractions (P < 0.05) and an attenuated contractile response to oxytocin. Myometrial mitochondrial copy number was reduced in older mice, although there were no age‐induced changes to the enzymatic activities of the mitochondrial electron transport chain complexes. In conclusion, 8‐month‐old mice provide a useful model of reproductive ageing. The present study has identified potential causes of labour dysfunction amenable to investigation in older primigravid women.

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Oxytocin depolarizes mitochondria in isolated myometrial cells

Abstract: Oxytocin is known to play important roles in uterine contractionsand resultant dissipation of the mitochondrial electrochemical gradient. ATP synthase is also stimulated, which would further contribute to a decrease in ψ m .

Cited by 14 publications

References 29 publications

Effect of Oxytocin on Neuroblastoma Cell Viability and Growth

Effect of Oxytocin on Neuroblastoma Cell Viability and Growth

Role of Mitochondria in Cerebral Vascular Function: Energy Production, Cellular Protection, and Regulation of Vascular Tone

Effect of reproductive ageing on pregnant mouse uterus and cervix

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