Elevated expression of the Ephx2 mRNA in the kidney of hypertensive ISIAH rats

Абрамова, Т. О.; Redina, Olga E.; Smolenskaya, S. É.; Al, Markel'

doi:10.1134/s0026893313060022

Cited by 15 publications

(5 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This allows us to assume that the sEH protein function in ISIAH rats is not changed, and the highly reliable increase in the transcription level of the Ephx2 gene in all analyzed tissues/organs of ISIAH rats may be related to the sequence features of the promoter region of this gene, or to the features of the signal regulation mechanisms of its expression. The second assumption can be based on the data we have on the localization of the Ephx2 gene in the genetic locus (QTL) on chromosome 15, which we previously associated with plasma corticosterone concentrations under the influence of emotional stress [61], as well as on data that the level of transcription of the Ephx2 gene significantly increases under the influence of emotional stress, which was shown when studying the level of its transcription in the renal medulla of ISIAH rats [62].…”

Section: Discussionmentioning

confidence: 99%

The differences in brain stem transcriptional profiling in hypertensive ISIAH and normotensive WAG rats

et al. 2019

View full text Add to dashboard Cite

Background: The development of essential hypertension is associated with a wide range of mechanisms. The brain stem neurons are essential for the homeostatic regulation of arterial pressure as they control baroreflex and sympathetic nerve activity. The ISIAH (Inherited Stress Induced Arterial Hypertension) rats reproduce the human stress-sensitive hypertensive disease with predominant activation of the neuroendocrine hypothalamic-pituitaryadrenal and sympathetic adrenal axes. RNA-Seq analysis of the brain stems from the hypertensive ISIAH and normotensive control WAG (Wistar Albino Glaxo) rats was performed to identify the differentially expressed genes (DEGs) and the main central mechanisms (biological processes and metabolic pathways) contributing to the hypertensive state in the ISIAH rats. Results: The study revealed 224 DEGs. Their annotation in databases showed that 22 of them were associated with hypertension and blood pressure (BP) regulation, and 61 DEGs were associated with central nervous system diseases. In accordance with the functional annotation of DEGs, the key role of hormonal metabolic processes and, in particular, the enhanced biosynthesis of aldosterone in the brain stem of ISIAH rats was proposed. Multiple DEGs associated with several Gene Ontology (GO) terms essentially related to modulation of BP were identified. Abundant groups of DEGs were related to GO terms associated with responses to different stimuli including response to organic (hormonal) substance, to external stimulus, and to stress. Several DEGs making the most contribution to the inter-strain differences were detected including the Ephx2, which was earlier defined as a major candidate gene in the studies of transcriptional profiles in different tissues/organs (hypothalamus, adrenal gland and kidney) of ISIAH rats. Conclusions:The results of the study showed that inter-strain differences in ISIAH and WAG brain stem functioning might be a result of the imbalance in processes leading to the pathology development and those, exerting the compensatory effects. The data obtained in this study are useful for a better understanding of the genetic mechanisms underlying the complexity of the brain stem processes in ISIAH rats, which are a model of stresssensitive form of hypertension.

show abstract

Section: Discussionmentioning

confidence: 99%

The differences in brain stem transcriptional profiling in hypertensive ISIAH and normotensive WAG rats

et al. 2019

View full text Add to dashboard Cite

show abstract

“…By using a gene microarray analysis, Seubert et al (2005) reported that sEH was significantly upregulated in the kidneys of spontaneously hypertensive rats (SHR) when compared with the non-hypertensive Wistar-Kyoto (WKY) rats. Also, Abramova et al (2013, 2017) found that the renal mRNA level and protein concentration of sEH were increased at in the inherited stress-induced arterial hypertension (ISIAH) rats when compared with the normative Wistar Albino Glaxo (WAG) rats. Tain et al (2015) reported that renal sEH was upregulated in dexamethasone- and a high fructose-induced rodent model of programmed hypertension.…”

Section: Preclinical Studies Of the Treatment Of Renal Dysfunction Bymentioning

confidence: 99%

Inhibition of Soluble Epoxide Hydrolase for Renal Health

Liu

2019

Front. Pharmacol.

View full text Add to dashboard Cite

A soluble epoxide hydrolase (sEH) mediates the metabolism of epoxy fatty acids to form the corresponding vicinal diols, which are usually inactive or less active than the epoxide substrates. The sEH enzyme presents in many organs, including but not limited to the liver, heart, spleen, lung, and kidney. Here we summarized the changes in the expression and activity of sEH in multiple renal diseases, such as acute kidney injury (AKI), diabetic nephrology (DN), chronic kidney diseases (CKD), hypertension-mediated renal damage, and other renal dysfunctions. We also discussed the pharmacologic effects and the underlying mechanisms of sEH inhibition by using an inhibitor of sEH and/or the generic deletion of sEH on multiple renal diseases. We believe that sEH is a potential therapeutic target for renal dysfunction although the target disease needs further investigation.

show abstract

“…A previous study pointed out that Ephx2-knockout mice did not develop heart failure and arrhythmia [31]. Studies also showed that specific sEH inhibitors could decrease blood pressure and repair damage in some organs, for example in heart, kidney, or vessels [32,33]. Thus, it is interesting to explore the role of Ephx2 gene in H 2 O 2 -induced IEC injury.…”

Section: Discussionmentioning

confidence: 99%

Soluble epoxide hydrolase (Ephx2) silencing attenuates the hydrogen peroxide-induced oxidative damage in IEC-6 cells

2021

Arch Med Sci

View full text Add to dashboard Cite

Introduction: Oxidative stress can cause intestinal disease. Soluble epoxide hydrolase (sEH, Ephx2) is related to cell apoptosis. The effect of Ephx2 on the H 2 O 2-induced oxidative damage remains unclear. Thus, we aimed to explore the effect of Ephx2 on oxidative damage and the underlying potential mechanism. Material and methods: The cell viability was determined using cell counting kit-8 (CCK-8) assay. The reactive oxygen species (ROS), apoptosis, and mitochondrial membrane potential (MMP) were examined using flow cyto metry analysis. Commercial kits were applied to respectively determine the lactate dehydrogenase (LDH) leakage, malondialdehyde (MDA) content, and superoxide dismutase (SOD) activity. The expressions of target factors were measured by conducting quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blot. Results: We found that knockdown of Ephx2 enhanced the viability of H 2 O 2-treated IEC-6 cells, and that si-Ephx2 reduced the ROS level, MMP loss, and apoptosis in comparison to the H 2 O 2 model group. Knockdown of Ephx2 was found to decrease LDH activity and MDA content, and to improve the SOD activity in comparison to those in the H 2 O 2 model group. Knockdown of Ephx2 reduced the expressions of Fas, Fasl, Bax, and cleavedcaspase-3 and elevated the expression of Bcl-2 in H 2 O 2-treated IEC-6 cells. Furthermore, we observed that knockdown of Ephx2 enhanced the phosphorylation of PI3K, Akt, and GSK3β, which were reduced by the treatment of H 2 O 2. In addition, the anti-apoptotic effect of si-Ephx2 was enhanced in the presence of AU-DA-pharmacological Ephx2 inhibitor. Conclusions: Ephx2 silencing inhibited H 2 O 2-induced oxidative damage. The PI3K/Akt/GSK3β pathway was related to the effect of si-Ephx2. Our study provided a potential target for the prevention of intestinal injury.

show abstract

Elevated expression of the Ephx2 mRNA in the kidney of hypertensive ISIAH rats

Cited by 15 publications

References 36 publications

The differences in brain stem transcriptional profiling in hypertensive ISIAH and normotensive WAG rats

The differences in brain stem transcriptional profiling in hypertensive ISIAH and normotensive WAG rats

Inhibition of Soluble Epoxide Hydrolase for Renal Health

Soluble epoxide hydrolase (Ephx2) silencing attenuates the hydrogen peroxide-induced oxidative damage in IEC-6 cells

Contact Info

Product

Resources

About