scholarly journals Gestational Hypoxia Inhibits Pregnancy-Induced Upregulation of Ca 2+ Sparks and Spontaneous Transient Outward Currents in Uterine Arteries Via Heightened Endoplasmic Reticulum/Oxidative Stress

Hypertension ◽  
2020 ◽  
Vol 76 (3) ◽  
pp. 930-942
Author(s):  
Xiang-Qun Hu ◽  
Rui Song ◽  
Monica Romero ◽  
Chiranjib Dasgupta ◽  
Joseph Min ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
High Altitude ◽  
Pregnancy Complications ◽  
Myogenic Tone ◽  
Vascular Adaptation ◽  
Uterine Arteries ◽  
Outward Currents ◽  
Low Altitude ◽  
Spontaneous Transient Outward Currents

Hypoxia during pregnancy profoundly affects uterine vascular adaptation and increases the risk of pregnancy complications, including preeclampsia and fetal intrauterine growth restriction. We recently demonstrated that increases in Ca 2+ sparks and spontaneous transient outward currents (STOCs) played an essential role in pregnancy-induced uterine vascular adaptation. In the present study, we hypothesize that gestational hypoxia suppresses Ca 2+ sparks/STOCs coupling leading to increased uterine vascular tone via enhanced endoplasmic reticulum (ER)/oxidative stress. Uterine arteries were obtained from nonpregnant and near-term pregnant sheep residing in low altitude or acclimatizing to high-altitude (3801 m) hypoxia for ≈110 days. High-altitude hypoxia suppressed pregnancy-induced upregulation of RyR1 and RyR2 (ryanodine receptor 1 and 2) protein abundance, Ca 2+ sparks, and STOCs in uterine arteries. Inhibition of Ca 2+ sparks/STOCs with the RyR inhibitor ryanodine significantly increased pressure-dependent myogenic tone in uterine arteries from low-altitude normoxic pregnant animals but not those from high-altitude hypoxic pregnant animals. Gestational hypoxia significantly increased ER/oxidative stress in uterine arteries. Of importance, the hypoxia-mediated suppression of Ca 2+ sparks/STOCs and increase in myogenic tone in uterine arteries of pregnant animals were reversed by inhibiting ER/oxidative stress. Of great interest, the impaired sex hormonal regulation of STOCs in high-altitude animals was annulled by scavenging reactive oxygen species but not by inhibiting ER stress. Together, the findings reveal the differential mechanisms of ER and oxidative stresses in suppressing Ca 2+ sparks/STOCs and increasing myogenic tone of uterine arteries in hypoxia during gestation, providing new insights into the understanding of pregnancy complications associated with hypoxia.

scholarly journals MicroRNA-210 Mediates Hypoxia-Induced Repression of Spontaneous Transient Outward Currents in Sheep Uterine Arteries During Gestation

Hypertension ◽  
2021 ◽  
Vol 77 (4) ◽  
pp. 1412-1427
Author(s):  
Xiang-Qun Hu ◽  
Chiranjib Dasgupta ◽  
Rui Song ◽  
Monica Romero ◽  
Sean M. Wilson ◽  
...  
Keyword(s):  
High Altitude ◽  
Intrauterine Growth Restriction ◽  
Hormonal Regulation ◽  
Outward Current ◽  
Transient Outward Current ◽  
Uterine Arteries ◽  
Outward Currents ◽  
Low Altitude ◽  
Spontaneous Transient Outward Currents

Hypoxia during pregnancy is a major contributor to the pathogenesis of preeclampsia and intrauterine growth restriction. Our recent studies revealed that pregnancy-induced uterine vascular adaptation depended on the enhanced Ca 2+ spark/spontaneous transient outward current (STOC) coupling and hypoxia during gestation diminished this adaption. In the present study, we test the hypothesis of a mechanistic link of microRNA-210 (miR-210) in hypoxia-impaired Ca 2+ spark/STOC coupling in uterine arteries. Pregnant ewes acclimatized to high-altitude (3801 m) hypoxia for ≈110 days significantly increased circulation levels of miR-210 in both the ewe and her fetus. Treatment of uterine arteries from high-altitude animals with the antagomir miR-210-LNA recovered hypoxia-repressed STOCs in pregnant ewes and restored the hormonal regulation of STOCs in nonpregnant animals. In uterine arteries from low-altitude control animals, miR-210 mimic suppressed STOCs in pregnant ewes and inhibited the hormonal regulation of STOCs in nonpregnant animals. Mechanistically, miR-210 directly targeted and downregulated type 2 ryanodine receptor and large-conductance Ca 2+ -activated K + channel β1 subunit, resulting in significant decreases in Ca 2+ sparks and STOCs in uterine arteries. In addition, miR-210 indirectly decreased STOCs by targeting ten-eleven translocation methylcytosine dioxygenase. Together, the present study revealed a mechanistic link of miR-210 in hypoxia-induced repression of Ca 2+ spark/STOC coupling in uterine arteries during gestation, providing novel insights into the understanding of pregnancy complications associated with hypoxia and the potential therapeutic targets.

scholarly journals Ryanodine receptor subtypes regulate Ca2+ sparks/spontaneous transient outward currents and myogenic tone of uterine arteries in pregnancy

2020 ◽  
Author(s):  
Rui Song ◽  
Xiang-Qun Hu ◽  
Monica Romero ◽  
Mark A Holguin ◽  
Whitney Kagabo ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
Uterine Artery ◽  
Vascular Tone ◽  
Myogenic Tone ◽  
Receptor Subtypes ◽  
Α Subunit ◽  
Uterine Arteries ◽  
Outward Currents ◽  
Pregnant Sheep ◽  
Spontaneous Transient Outward Currents

Abstract Aims Our recent study demonstrated that increased Ca2+ sparks and spontaneous transient outward currents (STOCs) played an important role in uterine vascular tone and haemodynamic adaptation to pregnancy. The present study examined the role of ryanodine receptor (RyR) subtypes in regulating Ca2+ sparks/STOCs and myogenic tone in uterine arterial adaptation to pregnancy. Methods and results Uterine arteries isolated from non-pregnant and near-term pregnant sheep were used in the present study. Pregnancy increased the association of α and β1 subunits of large-conductance Ca2+-activated K+ (BKCa) channels and enhanced the co-localization of RyR1 and RyR2 with the β1 subunit in the uterine artery. In contrast, RyR3 was not co-localized with BKCa β1 subunit. Knockdown of RyR1 or RyR2 in uterine arteries of pregnant sheep downregulated the β1 but not α subunit of the BKCa channel and decreased the association of α and β1 subunits. Unlike RyR1 and RyR2, knockdown of RyR3 had no significant effect on either expression or association of BKCa subunits. In addition, knockdown of RyR1 or RyR2 significantly decreased Ca2+ spark frequency, suppressed STOCs frequency and amplitude, and increased pressure-dependent myogenic tone in uterine arteries of pregnant animals. RyR3 knockdown did not affect Ca2+ sparks/STOCs and myogenic tone in the uterine artery. Conclusion Together, the present study demonstrates a novel mechanistic paradigm of RyR subtypes in the regulation of Ca2+ sparks/STOCs and uterine vascular tone, providing new insights into the mechanisms underlying uterine vascular adaptation to pregnancy.

scholarly journals Pregnancy Increases Ca 2+ Sparks/Spontaneous Transient Outward Currents and Reduces Uterine Arterial Myogenic Tone

Hypertension ◽  
2019 ◽  
Vol 73 (3) ◽  
pp. 691-702 ◽  
Author(s):  
Xiang-Qun Hu ◽  
Rui Song ◽  
Monica Romero ◽  
Chiranjib Dasgupta ◽  
Xiaohui Huang ◽  
...  
Keyword(s):  
Myogenic Tone ◽  
Outward Currents ◽  
Spontaneous Transient Outward Currents

Effects of antioxidant vitamins on newborn and placental traits in gestations at high altitude: comparative study in high and low altitude native sheep

2011 ◽  
Vol 23 (2) ◽  
pp. 285 ◽  
Author(s):  
Víctor H. Parraguez ◽  
Miljenko Atlagich ◽  
Oscar Araneda ◽  
Carlos García ◽  
Andrés Muñoz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Altitude ◽  
Sea Level ◽  
Maternal Plasma ◽  
Antioxidant Vitamins ◽  
Vitamin Supplementation ◽  
Plasma Vitamin ◽  
Oxidative Stress Biomarkers ◽  
Microscopic Evaluation ◽  
Low Altitude

The present study evaluated the hypothesis that the effects of hypoxia on sheep pregnancies at high altitude (HA) are mediated by oxidative stress and that antioxidant vitamins may prevent these effects. Both HA native and newcomer ewes were maintained at an altitude of 3589 m during mating and pregnancy. Control low altitude (LA) native ewes were maintained at sea level. Half of each group received daily oral supplements of vitamins C (500 mg) and E (350 IU) during mating and gestation. Near term, maternal plasma vitamin levels and oxidative stress biomarkers were measured. At delivery, lambs were weighed and measured, and placentas were recovered for macroscopic and microscopic evaluation. Vitamin concentrations in supplemented ewes were two- or threefold greater than in non-supplemented ewes. Plasma carbonyls and malondialdehyde in non-supplemented ewes were consistent with a state of oxidative stress, which was prevented by vitamin supplementation. Vitamin supplementation increased lamb birthweight and cotyledon number in both HA native and newcomer ewes, although placental weight and cotyledon surface were diminished. Placentas from vitamin-supplemented HA ewes were similar to those from ewes at sea level, making these placental traits (weight, number and diameter of cotyledons) similar to those from ewes at sea level. Vitamin supplementation had no effect on LA pregnancies. In conclusion, supplementation with vitamins C and E during pregnancy at HA prevents oxidative stress, improving pregnancy outcomes.

Abstract #403: The Glutathione Mimic Ebselen Inhibits Oxidative Stress but not Endoplasmic Reticulum Stress in Endothelial Cells.

2015 ◽  
Vol 21 ◽  
pp. 85-86
Author(s):  
William Kurban ◽  
Salma Makhoul Ahwach ◽  
Melanie Thomas ◽  
Luisa Onsteed-Haas ◽  
Michael Haas
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress

Testicular Injury Attenuated by Rapamycin Through Induction of Autophagy and Inhibition of Endoplasmic Reticulum Stress in Streptozotocin- Induced Diabetic Rats

2019 ◽  
Vol 19 (5) ◽  
pp. 665-675 ◽  
Author(s):  
Wenjiao Shi ◽  
Zhixin Guo ◽  
Ruixia Yuan
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Protective Effect ◽  
Er Stress ◽  
B Cell Lymphoma ◽  
Diabetic Rats ◽  
Pathological Changes ◽  
Rapamycin Treatment ◽  
Related Proteins

Background and Objective: This study investigated whether rapamycin has a protective effect on the testis of diabetic rats by regulating autophagy, endoplasmic reticulum stress, and oxidative stress. Methods: Thirty male Sprague-Dawley rats were randomly divided into three groups: control, diabetic, and diabetic treated with rapamycin, which received gavage of rapamycin (2mg.kg-1.d-1) after induction of diabetes. Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ, 65mg.Kg-1). All rats were sacrificed at the termination after 8 weeks of rapamycin treatment. The testicular pathological changes were determined by hematoxylin and eosin staining. The protein or mRNA expression of autophagy-related proteins (Beclin1, microtubule-associated protein light chain 3 (LC3), p62), ER stress marked proteins (CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP), caspase-12), oxidative stress-related proteins (p22phox, nuclear factor erythroid2-related factor 2 (Nrf2)) and apoptosis-related proteins (Bax, B cell lymphoma-2 (Bcl-2)) were assayed by western blot or real-time fluorescence quantitative PCR. Results: There were significant pathological changes in the testes of diabetic rats. The expression of Beclin1, LC3, Nrf2, Bcl-2 were significantly decreased and p62, CHOP, caspase12, p22phox, and Bax were notably increased in the testis of diabetic rats (P <0.05). However, rapamycin treatment for 8 weeks significantly reversed the above changes in the testis of diabetic rats (P <0.05). Conclusion: Rapamycin appears to produce a protective effect on the testes of diabetic rats by inducing the expression of autophagy and inhibiting the expression of ER-stress, oxidative stress, and apoptosis.

Sign in / Sign up

Export Citation Format

Share Document