17 -estradiol induces vasorelaxation by stimulating endothelial hydrogen sulfide release

Zhou, Kai; Gao, Qi; Zheng, Shunyi; Pan, Si-nian; Li, Ping; Suo, Kun; Simoncini, Tommaso; Wang, Tinghuai; Fu, Xiaodong

doi:10.1093/molehr/gas044

Cited by 42 publications

(35 citation statements)

References 45 publications

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“…Seeger et al reported that 2-ME induced endothelial COX-2 expression, leading to prostacyclin production [ 20 ]. In addition, we have discovered that E2 activated H 2 S release in endothelial cells [ 21 ]. Therefore, the role of these molecules in 2-ME actions should be further explored.…”

Section: Discussionmentioning

confidence: 99%

2-Methoxyestradiol Induces Vasodilation by Stimulating NO Release via PPARγ/PI3K/Akt Pathway

et al. 2015

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The endogenous estradiol metabolite 2-methoxyestradiol (2-ME) reduces atherosclerotic lesion formation, while the underlying mechanisms remain obscure. In this work, we investigated the vasodilatory effect of 2-ME and the role of nitric oxide (NO) involved. In vivo studies using noninvasive tail-cuff methods showed that 2-ME decreased blood pressure in Sprague Dawley rats. Furthermore, in vitro studies showed that cumulative addition of 2-ME to the aorta caused a dose- and endothelium-dependent vasodilation. This effect was unaffected by the pretreatment with the pure estrogen receptor antagonist ICI 182,780, but was largely impaired by endothelial nitric oxide synthase (eNOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) or by phosphoinositide 3-kinase (PI3K) inhibitor wortmannin (WM). Moreover, 2-ME（10−7 ∼10−5 M）enhanced phosphorylation of Akt and eNOS and promoted NO release from cultured human umbilical endothelial cells (HUVECs). These effects were blocked by PI3K inhibitor WM, or by the transfection with Akt specific siRNA, indicating that endothelial Akt/eNOS/NO cascade plays a crucial role in 2-ME-induced vasodilation. The peroxisome proliferator-activated receptor γ (PPARγ) mRNA and protein expression were detected in HUVECs and the antagonist GW9662 or the transfection with specific PPARγ siRNA inhibited 2-ME-induced eNOS and Akt phosphorylation, leading to the impairment of NO production and vasodilation. In conclusion, 2-ME induces vasodilation by stimulating NO release. These actions may be mediated by PPARγ and the subsequent activation of Akt/eNOS cascade in vascular endothelial cells.

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Section: Discussionmentioning

confidence: 99%

2-Methoxyestradiol Induces Vasodilation by Stimulating NO Release via PPARγ/PI3K/Akt Pathway

et al. 2015

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“…H 2 S levels were measured as previously described [13]. Amperometric H 2 S sensors (ISO-H 2 S-100, World Precision Instruments, Sarasota, FL, USA) were used for the real-time measurement of dissolved H 2 S concentration in the medium.…”

Section: Methodsmentioning

confidence: 99%

Hydrogen Sulfide Inhibits Abnormal Proliferation of Lymphocytes via AKT/GSK3� Signal Pathway in Systemic Lupus Erythematosus Patients

Han

Zeng

Tan

et al. 2013

Cell Physiol Biochem

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Background/Aim: The abnormal activation of the AKT/GSK3β signal pathway in lymphocytes from systemic lupus erythematosus (SLE) patients plays an important role in the pathogenesis of the disease. Recently Hydrogen sulfide (H₂S) has been recognized as a crucial gaseous signaling molecule, involved in regulation of cell proliferation. However, the role of H₂S in regulating the abnormal activation of lymphocytes from SLE patients has not been established. This study was conducted to investigate the effect of H₂S on lymphocytes and to explore the mechanisms involved. Methods: The lymphocytes were isolated from SLE patients with or without renal disease and healthy controls. The cells were treated as indicated in each experiment. Cell viability was analyzed by CCK-8. Cell cycle distribution was determined by flow cytometry. Western blot was used to detect the expression of phosphorylated AKT (ser473), GSK3β (ser9) and CDK2, p27^Kip1 and p21^WAF1/CIP1. Results: Our findings showed that proliferation of lymphocytes was stimulated following treatment with NaHS (a H₂S donor) at low NaHS concentrations (<1mM) but inhibited at high NaHS concentrations (>2mM). Similar results were observed using GYY4137, which is a slow-releasing H₂S donor. Pretreatment of lymphocytes from SLE patients with NaHS at high concentrations prior to exposure to phytohemagglutinin (PHA) significantly attenuated proliferation, evidenced by decrease in cell viability and S phase distribution of cell cycle. Pretreatment with NaHS decreased PHA-induced expression of CDK2, phosphorylation levels of AKT (ser473) and GSK3β (ser9) and increased the expression of p27^Kip1 and p21^WAF1/CIP1. Moreover, pretreatment with NaHS blunted the stimulation of SLE lymphocyte proliferation by GSK3β inhibitor lithium chloride. Conclusion: These results demonstrate that H₂S inhibits the abnormal activation of lymphocytes from SLE patients throuqh the AKT/GSK3β signal pathway.

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“…Remodeling of capillary geometry and a lower maximal oxygen uptake has been found in the tibialis anterior muscle of RLS patients. 28 Estrogen has been shown to improve vascularization 29 and to also, via increased nitric oxide production and vasodilatation, 30 ultimately increase the oxygen supply. Nitric oxide has recently been reported to influence dopaminergic processes, promoting speculation on that the actions of this molecule may provide a link between the peripheral and central hypotheses of the origin of RLS/PLM.…”

Section: Discussionmentioning

confidence: 99%

Periodic Limb Movements Are Associated with Vasomotor Symptoms

Wesström

Ulfberg²,

Sundström‐Poromaa

et al. 2014

Journal of Clinical Sleep Medicine

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diagnosis of periodic limb movement disorder (PLMD) is established when the affected individual also has insomnia and/or excessive daytime drowsiness. By subjective reports, the prevalence of PLMD has been estimated to be 3.9% in the general population. Restless legs syndrome (RLS) is a common sensory-motor disorder that produces uncomfortable sensations and a constant urge to move the lower limbs, and has a typical diurnal pattern with a peak of symptoms during rest periods in the evening and at night. RLS has also been reported to be associated with cardiovascular disease (CVD). 8 In contrast to PLMs, the diagnosis of RLS is based on the patient's subjective symptoms. PLMs are related to RLS, and the majority of patients with RLS display PLMs during sleep. 9 Prior studies have discussed the S C I E N T I F I C I N V E S T I G A T I O N SP eriodic limb movements (PLMs) during sleep were fi rst described in 1953 as "nocturnal myoclonus," and were at that time thought to have similarities to nocturnal epilepsy. 1The pathophysiological mechanisms of PLMs are unclear, but abnormal hyperexcitability (or diminished inhibition) in the lumbosacral and cervical segments of the spinal cord have been hypothesized to be possible causes.2 PLMs are characterized by involuntary movements of the lower extremities, specifi cally the toes, ankle, knees, and hips, typically lasting between 0.5 and 10 seconds. The patient is usually unaware of the limb movements or the frequent sleep disruptions, and PLMs are often an incidental fi nding at polysomnography (PSG).3 PLMs may cause microarousals, leaving the affected patient fatigued the following day. Previously, it was assumed that PLMs were the cause of these arousals, but more recent studies have revealed that PLMs and arousals are associated in a more complex and non-unidirectional manner. Arousals can occur before, during, and after leg movements, indicating that the phenomenon is associated with an underlying arousal disorder. 4 The exact prevalence of PLMs is unknown. They appear to be rare in children, to progress with advancing age, and to be more common in females than in males. 5,6 In studies where PLMs have been objectively documented (PLM episodes/h of sleep > 5), the prevalence was 5% to 6% in younger adults, and 25% to 58% among elderly people. BRIEF SUMMARYCurrent Knowledge/Study Rationale: Sleep disturbances affect a substantial fraction of women during the menopausal transition, and female sex hormones are possibly involved in the origin of PLMs. It is currently unknown whether PLMs are associated with the menopausal transition and/or concomitant vasomotor symptoms. Study Impact: This study shows an association between symptoms related to declining levels of estrogen, i.e. vasomotor symptoms, and PLMs. Future studies should address the possibility of using hormone replacement therapy in postmenopausal women with PLMD.

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17 -estradiol induces vasorelaxation by stimulating endothelial hydrogen sulfide release

Cited by 42 publications

References 45 publications

2-Methoxyestradiol Induces Vasodilation by Stimulating NO Release via PPARγ/PI3K/Akt Pathway

2-Methoxyestradiol Induces Vasodilation by Stimulating NO Release via PPARγ/PI3K/Akt Pathway

Hydrogen Sulfide Inhibits Abnormal Proliferation of Lymphocytes via AKT/GSK3� Signal Pathway in Systemic Lupus Erythematosus Patients

Periodic Limb Movements Are Associated with Vasomotor Symptoms

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