Oestrogen inhibits salt-dependent hypertension by suppressing GABAergic excitation in magnocellular AVP neurons

2020 ◽  
Author(s):  
Xiangyan Jin ◽  
Woong Bin Kim ◽  
Mi-Na Kim ◽  
Won Woo Jung ◽  
Hyung Kyung Kang ◽  
...  
Keyword(s):  
Antihypertensive Effect ◽  
Protective Role ◽  
Ovariectomized Rats ◽  
Equilibrium Potential ◽  
Salt Treatment ◽  
Abundant Evidence ◽  
Plasma Arginine ◽  
Depressor Effect

Abstract Aims Abundant evidence indicates that oestrogen (E2) plays a protective role against hypertension. Yet, the mechanism underlying the antihypertensive effect of E2 is poorly understood. In this study, we sought to determine the mechanism through which E2 inhibits salt-dependent hypertension. Methods and results To this end, we performed a series of in vivo and in vitro experiments employing a rat model of hypertension that is produced by deoxycorticosterone acetate (DOCA)-salt treatment after uninephrectomy. We found that E2 prevented DOCA-salt treatment from inducing hypertension, raising plasma arginine-vasopressin (AVP) level, enhancing the depressor effect of the V1a receptor antagonist (Phenylac1,D-Tyr(Et)2,Lys6,Arg8,des-Gly9)-vasopressin, and converting GABAergic inhibition to excitation in hypothalamic magnocellular AVP neurons. Moreover, we obtained results indicating that the E2 modulation of the activity and/or expression of NKCC1 (Cl− importer) and KCC2 (Cl− extruder) underpins the effect of E2 on the transition of GABAergic transmission in AVP neurons. Lastly, we discovered that, in DOCA-salt-treated hypertensive ovariectomized rats, CLP290 (prodrug of the KCC2 activator CLP257, intraperitoneal injections) lowered blood pressure, and plasma AVP level and hyperpolarized GABA equilibrium potential to prevent GABAergic excitation from emerging in the AVP neurons of these animals. Conclusion Based on these results, we conclude that E2 inhibits salt-dependent hypertension by suppressing GABAergic excitation to decrease the hormonal output of AVP neurons.

IN VITRO UPTAKE OF TRITIATED OESTRADIOL BY THE ANTERIOR HYPOTHALAMUS AND HYPOPHYSIS OF THE RAT

1970 ◽  
Vol 64 (4) ◽  
pp. 687-695 ◽  
Author(s):  
Junzo Kato
Keyword(s):  
Incubation Medium ◽  
Posterior Hypothalamus ◽  
Anterior Hypothalamus ◽  
Ovariectomized Rats ◽  
Free Medium ◽  
Cortex Cerebri ◽  
Anterior Hypophysis ◽  
In Vitro Uptake

ABSTRACT The anterior, middle, and posterior hypothalamus, the cortex cerebri, the anterior hypophysis as well as the diaphragm of adult ovariectomized rats were incubated in vitro with tritiated 17β-oestradiol. The uptake of tritiated oestradiol was differentially distributed intracerebrally with higher accumulation in the anterior hypothalamus and the hypophysis. Lowering the temperature of the incubation medium caused a reduction in the uptake of radioactivity by the anterior hypothalamus as compared to that found in other brain tissues. Tritiated oestradiol taken up in vitro by the anterior hypothalamus and the hypophysis tended to be retained after further incubation in a steroid-free medium. The addition of non-radioactive 17β-oestradiol to the medium inhibited the uptake of tritiated oestradiol by these tissues. Moreover, pretreatment with non-radioactive 17β-oestradiol in vivo prevented the preferential accumulation of tritiated oestradiol in vitro in the anterior hypothalamus and the hypophysis. These results indicate that oestradiol is preferentially taken up in vitro by the anterior hypothalamus and the hypophysis of the rat.

scholarly journals Identification of the Active Ingredient and Beneficial Effects of Vitex rotundifolia Fruits on Menopausal Symptoms in Ovariectomized Rats

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1033
Author(s):  
Ji Hwan Lee ◽  
Sullim Lee ◽  
Quynh Nhu Nguyen ◽  
Hung Manh Phung ◽  
Myoung-Sook Shin ◽  
...  
Keyword(s):  
Weight Gain ◽  
Body Weight Gain ◽  
Animal Experiments ◽  
Ovariectomized Rats ◽  
Biological Functions ◽  
Menopausal Syndrome ◽  
Active Constituents ◽  
Mcf 7

Estrogen replacement therapy is a treatment to relieve the symptoms of menopause. Many studies suggest that natural bioactive ingredients from plants resemble estrogen in structure and biological functions and can relieve symptoms of menopause. The fruit of V. rotundifolia, called “Man HyungJa” in Korean, is a traditional medicine used to treat headache, migraine, eye pain, neuralgia, and premenstrual syndrome in Korea and China. The aim of the present study was to confirm that V. rotundifolia fruit extract (VFE) exerts biological functions similar to those of estrogen in menopausal syndrome. We investigated its in vitro effects on MCF-7 cells and in vivo estrogen-like effects on weight gain and uterine contraction in ovariectomized rats. Using the polar extract, the active constituents of VFE (artemetin, vitexicarpin, hesperidin, luteolin, vitexin, and vanillic acid) with estrogen-like activity were identified in MCF-7 cells. In animal experiments, the efficacy of VFE in ameliorating body weight gain was similar to that of estrogen, as evidenced from improvements in uterine atrophy. Vitexin and vitexicarpin are suggested as the active constituents of V. rotundifolia fruits.

MyD88-Dependent Glucose Restriction and Itaconate Production Control Brucella Infection

2021 ◽  
Author(s):  
Carolyn A. Lacey ◽  
Bárbara Ponzilacqua-Silva ◽  
Catherine A. Chambers ◽  
Alexis S. Dadelahi ◽  
Jerod A. Skyberg
Keyword(s):  
Glucose Transporter ◽  
Production Control ◽  
Brucella Melitensis ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Ifn Γ ◽  
Glucose Restriction ◽  
Myd88 Signaling

Brucellosis is one of the most common global zoonoses and is caused by facultative intracellular bacteria of the genus Brucella . Numerous studies have found that MyD88 signaling contributes to protection against Brucella , however the underlying mechanism has not been entirely defined. Here we show that MyD88 signaling in hematopoietic cells contributes both to inflammation and to control of Brucella melitensis infection in vivo . While the protective role of MyD88 in Brucella infection has often been attributed to promotion of IFN-γ production, we found that MyD88 signaling restricts host colonization by B. melitensis even in the absence of IFN-γ. In vitro , we show that MyD88 promotes macrophage glycolysis in response to B. melitensis . Interestingly, a B. melitensis mutant lacking the glucose transporter, GluP, was more highly attenuated in MyD88 -/- than in WT mice, suggesting MyD88 deficiency results in an increased availability of glucose in vivo which Brucella can exploit via GluP. Metabolite profiling of macrophages identified several metabolites regulated by MyD88 in response to B. melitensis , including itaconate. Subsequently, we found that itaconate has antibacterial effects against Brucella and also regulates the production of pro-inflammatory cytokines in B. melitensis -infected macrophages. Mice lacking the ability to produce itaconate were also more susceptible to B. melitensis in vivo . Collectively, our findings indicate that MyD88-dependent changes in host metabolism contribute to control of Brucella infection.

Cardiotoxicity and myocardial infarction-associated DNA damage induced by thiamethoxam in vitro and in vivo: Protective role ofTrigonella foenum-graecumseed-derived polysaccharide

2018 ◽  
Vol 34 (3) ◽  
pp. 271-282 ◽  
Author(s):  
Amal Feki ◽  
Hajer Ben Saad ◽  
Intidhar Bkhairia ◽  
Naourez Ktari ◽  
Manel Naifar ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Dna Damage ◽  
Protective Role

scholarly journals Protective Role of Coenzyme Q10 in Acute Sepsis-Induced Liver Injury in BALB/c Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Qian-wei Li ◽  
Qin Yang ◽  
Hong-Yang Liu ◽  
Yu-ling Wu ◽  
Yu-Hua Hao ◽  
...  
Keyword(s):  
Liver Injury ◽  
Coenzyme Q10 ◽  
Cecal Ligation ◽  
Protective Role ◽  
Hepatic Tissue ◽  
Control Group ◽  
Cecal Ligation And Puncture ◽  
Sequestosome 1

Sepsis increases the risk of the liver injury development. According to the research works, coenzyme Q10 exhibits hepatoprotective properties in vivo as well as in vitro. Current work aimed at investigating the protective impacts of coenzyme Q10 against liver injury in septic BALB/c mice. The male BALB/c mice were randomly segregated into 4 groups: the control group, the coenzyme Q10 treatment group, the puncture and cecal ligation group, and the coenzyme Q10+cecal ligation and puncture group. Cecal ligation and puncture was conducted after gavagaging the mice with coenzyme Q10 during two weeks. Following 48 h postcecal ligation and puncture, we estimated hepatic biochemical parameters and histopathological changes in hepatic tissue. We evaluated the expression of factors associated with autophagy, pyroptosis, and inflammation. Findings indicated that coenzyme Q10 decreased the plasma levels in alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase in the cecal ligation and puncture group. Coenzyme Q10 significantly inhibited the elevation of sequestosome-1, interleukin-1β, oligomerization domain-like receptor 3 and nucleotide-binding, interleukin-6, and tumor necrosis factor-α expression levels; coenzyme Q10 also increased beclin 1 levels. Coenzyme Q10 might be a significant agent in the treatment of liver injury induced by sepsis.

scholarly journals In Vitro and in Vivo Characterisation of P. Aeruginosa Oxidoreductase Enzymes in Pathogenesis and Therapy

2021 ◽  
Author(s):  
◽  
Laura Kay Green
Keyword(s):  
Bacterial Pathogen ◽  
Protective Role ◽  
Infection Model ◽  
Virulence Determinants ◽  
Genetic Redundancy ◽  
Quinone Oxidoreductase ◽  
Native Form ◽  
Enzyme Prodrug Therapy

<p>Pseudomonas aeruginosa, an increasingly multi-drug resistant human pathogen, is now one of the top three causes of opportunistic infection and there is much interest in identifying novel therapeutic targets for treatment. As a bacterial pathogen, P. aeruginosa encounters innate immune system defences and must continue to adapt to its defence strategies to accommodate the ever-changing environment. Though P. aeruginosa virulence determinants have been heavily characterised over the last several decades, most recent work acknowledges the complex interaction between the human host and the pathogen as an on-going dialogue of virulence factors adapting to the continuum that is the immune response. A major challenge that P. aeruginosa must overcome are reactive oxygen species (ROS) that are released at all stages of infection. Based on previous work which demonstrated a role for soluble nitro- and quinone oxidoreductase (NQOR) enzymes in protecting a related bacterium (Pseudomonas putida) from oxidative stress, we hypothesized that P. aeruginosa would similarly utilize NQORs to withstand ROS. This thesis seeks to understand the role of ROS-protecting enzymes in pathogenesis as well as their potential applications in a therapeutic context. Several NQORs of P. aeruginosa were identified to possess biochemical characteristics consistent with the enzymatic capacity to indirectly reduce reactive species like H₂O₂. However, when individual genes encoding NQORs were deleted from P. aeruginosa, no apparent H₂O₂ sensitivity was seen. In contrast, when candidate genes were over-expressed, certain NQOR enzymes conferred the ability to tolerate H₂O₂ challenge at low concentrations; indicating that these NQORs may play a protective role whose effects are masked in vitro by genetic redundancy as well as a highly active endogenous catalase. By developing a novel in vivo cell culture infection model, the survival of P. aeruginosa post exposure to immunocompetent murine macrophages was also assessed. This not only demonstrated that several putative NQORs were activated in the presence of macrophages but also that an in vivo modelling system is likely to be more appropriate for discovering virulence determinants. In a different aspect of this study it was investigated whether the reductive capacity of the P. aeruginosa-derived NQORs might hold potential for gene-directed enzyme-prodrug therapy (GDEPT). Prodrugs, such as 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954) or the nitro-chloromethyl benzindoline SN 26438, are nontoxic in their native form, but become highly toxic upon reduction of their nitro functional groups. The P. aeruginosa NQORs, were tested to identify enzymes capable of efficient activation of CB1954 or SN 26438. Although none of these enzymes exhibited greater activity with CB1954 than the “best in class” Eschericha coli enzymes NfsA or NfsB, the P. aeruginosa NfsB orthologue (PA5190) demonstrated greater than 20-fold improved activity over NfsB from Escherichia coli in its ability to sensitise human cells to SN 26438. This finding offers promise for development of PA5190 and SN 26438 as a novel enzyme-prodrug paradigm for GDEPT.</p>

MicroRNA-204-3p Attenuates High Glucose-Induced MPC5 Podocytes Apoptosis by Targeting Braykinin B2 Receptor

2018 ◽  
Vol 127 (06) ◽  
pp. 387-395 ◽  
Author(s):  
Xu Han ◽  
Qiaobei Li ◽  
Chunyan Wang ◽  
Yinyan Li
Keyword(s):  
Cell Viability ◽  
High Glucose ◽  
Protective Role ◽  
Luciferase Reporter ◽  
Gene And Protein Expression ◽  
Glucose Treatment ◽  
Apoptosis Gene ◽  
Induced Apoptosis

Abstract Background Previous study has been reported that braykinin B2 receptor (Bdkrb2) involves in high glucose-induced renal and podocytes injuries. However, there have been some studies with contradictory results that Bdkrb2 has a protective effect on hyperglycemia-induced injuries in vivo and in vitro. The purpose of the present study was carried out to further investigate the post-transcriptional regulatory mechanism of microRNA (miR) in high glucose-treated podocytes by targeting Bdkrb2 signaling in vitro. Methods The CCK-8 and flow cytometry were performed to measure the cell viability and apoptosis. Gene and protein expression were assayed by RT-qPCR and western blotting, respectively. Results High glucose treatment decreased cell viability and induced membrane and DNA damage, as well as apoptosis in podocytes. High glucose treatment also increased the expression of Bdkrb2, which was blocked by miR-204-3p mimics transfection in podocytes. Bioinformatics and luciferase reporter activity showed that miR-204-3p was directly targeted to the 3′-untranslated region (3′-UTR) of Bdkrb2. High glucose-induced apoptosis and dysfunction in podocytes were reserved by miR-204-3p mimics transfection, while the effects of miR-204-3p mimics in high glucose-treated podocytes were neutralized by overexpressed Bdkrb2. Conclusions These findings suggested that miR-204-3p may play a protective role in high glucose-induced apoptosis and dysfunction in podocytes through down-regulation of Bdkrb2.

scholarly journals Estrogen modulates the recruitment of myelopoietic cell progenitors in rat through a stromal cell-independent mechanism involving apoptosis

Blood ◽  
1996 ◽  
Vol 87 (7) ◽  
pp. 2683-2692 ◽  
Author(s):  
NK Shevde ◽  
JW Pike
Keyword(s):  
Estrogen Receptor ◽  
Ovarian Function ◽  
Morphological Changes ◽  
Estrogen Treatment ◽  
Ovariectomized Rats ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Protective Effects ◽  
Hematopoietic Stem

Loss of ovarian function leads to a significant increase in the number of bone-resorbing osteoclasts. Estrogen replacement is known to manifest bone protective effects in the treatment of postmenopausal osteoporosis. In the present study, we used ovariectomized rats to examine the effects of estrogen loss at the osteoclast progenitor colony forming unit-granulocyte macrophage (CFU-GM) level. A significant increase in CFU-GM number was observed as early as 7 days following ovariectomy, and correlated directly with an increase in the number of osteoclast-like cells generated in marrow cultures. The increase in CFU-GM following ovariectomy was abrogated in animals that received estrogen treatment in vivo. A similar suppressive effect was observed on CFU-GM number when ovariectomized rat marrow was treated with estrogen in vitro. This effect was blocked in the presence of the estrogen antihormone ICI 164,384. Thus, the data suggest the possibility that estrogen exerts a direct effect on osteoclast progenitors, and does so through the estrogen receptor-mediated mechanism. Ovariectomy also led to an increase in the early hematopoietic stem/progenitor cell population (Thy 1.1+ cells) as determined by FLOW cytometry methods. Morphological changes as well as terminal deoxynucleotidyl transferase assays revealed that estrogen treatment negated growth factor-induced proliferation of these early progenitors by promoting apoptosis. The cellular effects of estrogen in vitro together with the immunocytochemical detection of the estrogen receptor in these cells, strongly support the contention that in addition to osteoclast progenitors such as CFU-GM, earlier hematopoietic progenitors are also unique cellular targets for estrogen action.

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