scholarly journals The perplexing pregnancy disorder preeclampsia: what next?

2018 ◽  
Vol 50 (6) ◽  
pp. 459-467 ◽  
Author(s):  
James M. Roberts
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Animal Experimentation ◽  
Placental Dysfunction ◽  
Prediction And Prevention ◽  
Inflammatory Activation ◽  
Cause Of Deaths ◽  
And Oxidative Stress ◽  
New Onset

Preeclampsia occurs in 3–5% of pregnancies and is a leading cause of deaths of mothers and their infants worldwide. It was initially described over 100 yr ago as a pregnancy abnormality defined by new-onset hypertension and proteinuria. Progress in understanding the pathophysiology was impeded by attention to these diagnostic findings. Hypertension and proteinuria were actually serendipitously recognized components of a complex multisystemic syndrome and not especially pertinent to outcome. With the recognition of inflammatory activation with consequent endothelial dysfunction 30 yr ago redirection of research resulted in an explosive increase in understanding of the disorder. The immunological origins, the role of the placenta and its functional alterations due to endoplasmic reticulum and oxidative stress, identification of placental products linking placental dysfunction to maternal systemic pathophysiology, and the role of the maternal constitution have been elegantly demonstrated by clinical, fundamental, and epidemiological findings and clever animal experimentation. Nonetheless, this increase in knowledge has not translated into improved prediction and prevention of preeclampsia. In this presentation the likelihood is discussed that this is secondary to a much greater complexity than has been previously considered and the existence of subtypes of preeclampsia that may not share an identical pathophysiology. The necessity for collaboration with data, sample, and intellectual sharing is addressed. An approach to addressing the challenges posed to such collaboration exemplified by the Global Pregnancy Collaboration is presented.

Abstract 357: Hepatic ERK2 Suppresses Endoplasmic Reticulum Stress, Leading to Protection from Oxidative Stress and Endothelial Dysfunction

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Takehiko Kujiraoka ◽  
Yasushi Satoh ◽  
Makoto Ayaori ◽  
Yasunaga Shiraishi ◽  
Yuko Arai-Nakaya ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Endoplasmic Reticulum ◽  
Fatty Acid ◽  
Endothelial Dysfunction ◽  
Er Stress ◽  
Vascular Complications ◽  
Metabolic Remodeling ◽  
And Oxidative Stress

Background Insulin signaling comprises 2 major cascades, the IRS/PI3K/Akt and Ras/Raf/MEK/ERK pathways. Many studies on the tissue-specific effects of the former pathway had been conducted, however, the role of the latter cascade in tissue-specific insulin resistance had not been investigated. High glucose/fatty acid toxicity, inflammation and oxidative stress, all of which are associated with insulin resistance, can activate ERK. Liver plays a central role of metabolism and hepatosteatosis (HST) is associated with vascular diseases. The aim of this study is to elucidate the role of hepatic ERK2 in HST, metabolic remodeling and endothelial dysfunction. Methods Serum biomarkers of vascular complications in human were compared between subjects with and without HST diagnosed by echography for regular medical checkup. Next, we created liver-specific ERK2 knockout mice (LE2KO) and fed them with a high-fat/high-sucrose diet (HFHSD) for 20 weeks. The histological analysis, the expression of hepatic sarco/endoplasmic reticulum (ER) Ca 2+ -ATPase 2 (SERCA2) and glucose-tolerance/insulin-sensitivity (GT/IS) were tested. Vascular superoxide production and endothelial function were evaluated with dihydroethidium staining and isometric tension measurement of aorta. Results The presence of HST significantly increased HOMA-IR, an indicator of insulin resistance or atherosclerotic index in human. HFHSD-fed LE2KO revealed a marked exacerbation in HST and metabolic remodeling represented by the impairment of GT/IS, elevated serum free fatty acid and hyperhomocysteinemia without changes in body weight, blood pressure and serum cholesterol/triglyceride levels. In the HFHSD-fed LE2KO, mRNA and protein expressions of hepatic SERCA2 were significantly decreased, which resulted in hepatic ER stress. Induction of vascular superoxide production and remarkable endothelial dysfunction were also observed in them. Conclusions Hepatic ERK2 revealed the suppression of hepatic ER stress and HST in vivo , which resulted in protection from vascular oxidative stress and endothelial dysfunction. HST with hepatic ER stress can be a prominent risk of vascular complications by metabolic remodeling and oxidative stress in obese-related diseases.

Rhabdomyolysis induced AKI via the regulation of endoplasmic reticulum stress and oxidative stress in PTECs

RSC Advances ◽  
2016 ◽  
Vol 6 (111) ◽  
pp. 109639-109648 ◽  
Author(s):  
Yuying Feng ◽  
Liang Ma ◽  
Linfeng Liu ◽  
Hyokyoung Grace Hong ◽  
Xuemei Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
And Oxidative Stress ◽  
Stress Activation

Mechanism for the role of ER stress and oxidative stress activation in rhabdomyolysis-associated AKI.

scholarly journals Disruption of Placental Homeostasis Leads to Preeclampsia

2020 ◽  
Vol 21 (9) ◽  
pp. 3298
Author(s):  
Akitoshi Nakashima ◽  
Tomoko Shima ◽  
Sayaka Tsuda ◽  
Aiko Aoki ◽  
Mihoko Kawaguchi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Mouse Models ◽  
Fetal Growth ◽  
Well Being ◽  
Environmental Stressors ◽  
And Oxidative Stress ◽  
Human And Mouse

Placental homeostasis is directly linked to fetal well-being and normal fetal growth. Placentas are sensitive to various environmental stressors, including hypoxia, endoplasmic reticulum stress, and oxidative stress. Once placental homeostasis is disrupted, the placenta may rebel against the mother and fetus. Autophagy is an evolutionally conservative mechanism for the maintenance of cellular and organic homeostasis. Evidence suggests that autophagy plays a crucial role throughout pregnancy, including fertilization, placentation, and delivery in human and mouse models. This study reviews the available literature discussing the role of autophagy in preeclampsia.

The role of DRAM1 in mitophagy contributes to preeclampsia regulation in mice

2019 ◽  
Author(s):  
Guoqing Chen ◽  
Ying Lin ◽  
Lu Chen ◽  
Fa Zeng ◽  
Li Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Blood Lipid ◽  
Pregnancy Complication ◽  
Urine Protein ◽  
Protein Levels ◽  
High Level ◽  
And Oxidative Stress ◽  
New Onset

Abstract Background: Preeclampsia (PE) is a pregnancy complication that is diagnosed by the new onset of hypertension and proteinuria. Although the pathogenesis of PE is still not fully understood, growing evidence indicates that oxidative stress and mitochondrial dysfunction may contribute to the progression of PE. Therefore, we aimed to determine the role of mitophagy in mitochondrial dysfunction and oxidative stress in PE. Moreover, we aimed to evaluate the role of DNA damage-regulated autophagy modulator 1 (DRAM1) in the development of PE. Results: In this study, we first constructed a mouse model of PE induced by Hif-1α and found a high level of oxidative stress, apoptosis and mitochondrial dysfunction in the placentas of PE mice. Additionally, the activity of mitophagy was decreased, and the level of DRAM1 was significantly decreased in the placentas of PE mice. To further explore the role of DRAM1 in mitophagy, DRAM1 was overexpressed in the placental tissues of PE mice. It was found that the overexpression of DRAM1 effectively improved the symptoms of PE mice and that blood lipid and urine protein levels were significantly reduced. Furthermore, DRAM1 overexpression also improved mitochondrial function and reduced oxidative stress in the placentas of PE mice. In addition, it improved mitochondrial fusion and fission and enhanced mitophagy.Conclusions: our results indicate a key role of DRAM1 in mitophagy in contributing to the regulation of PE. To our knowledge, this is the first study to confirm the role of DRAM1 in PE, and the study provides a new understanding of the pathophysiological mechanisms of PE.

Inhibition of microRNA-155 Alleviates Neurological Dysfunction Following Transient Global Ischemia and Contribution of Neuroinflammation and Oxidative Stress in the Hippocampus

2020 ◽  
Vol 25 (40) ◽  
pp. 4310-4317 ◽  
Author(s):  
Lichao Sun ◽  
Shouqin Ji ◽  
Jihong Xing
Keyword(s):  
Oxidative Stress ◽  
Brain Edema ◽  
Severity Score ◽  
Global Ischemia ◽  
Signal Pathways ◽  
Neurological Severity Score ◽  
Tnf Α ◽  
Transient Global Ischemia ◽  
And Oxidative Stress

Background/Aims: Central pro-inflammatory cytokine (PIC) signal is involved in neurological deficits after transient global ischemia induced by cardiac arrest (CA). The present study was to examine the role of microRNA- 155 (miR-155) in regulating IL-1β, IL-6 and TNF-α in the hippocampus of rats with induction of CA. We further examined the levels of products of oxidative stress 8-isoprostaglandin F2α (8-iso PGF2α, indication of oxidative stress); and 8-hydroxy-2’-deoxyguanosine (8-OHdG, indication of protein oxidation) after cerebral inhibition of miR-155. Methods: CA was induced by asphyxia and followed by cardiopulmonary resuscitation in rats. ELISA and western blot analysis were used to determine the levels of PICs and products of oxidative stress; and the protein expression of NADPH oxidase (NOXs) in the hippocampus. In addition, neurological severity score and brain edema were examined to assess neurological functions. Results: We observed amplification of IL-1β, IL-6 and TNF-α along with 8-iso PGF2α and 8-OHdG in the hippocampus of CA rats. Cerebral administration of miR-155 inhibitor diminished upregulation of PICs in the hippocampus. This also attenuated products of oxidative stress and upregulation of NOX4. Notably, inhibition of miR-155 improved neurological severity score and brain edema and this was linked to signal pathways of PIC and oxidative stress. Conclusion: We showed the significant role of blocking miR-155 signal in improving the neurological function in CA rats likely via inhibition of signal pathways of neuroinflammation and oxidative stress, suggesting that miR-155 may be a target in preventing and/or alleviating development of the impaired neurological functions during CA-evoked global cerebral ischemia.

LncRNA SNHG12 Improves Cerebral Ischemic-reperfusion Injury by Activating SIRT1/FOXO3a Pathway through I nhibition of Autophagy and Oxidative Stress

2020 ◽  
Vol 17 (4) ◽  
pp. 394-401
Author(s):  
Yuanhua Wu ◽  
Yuan Huang ◽  
Jing Cai ◽  
Donglan Zhang ◽  
Shixi Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Cell Activity ◽  
Ht22 Cells ◽  
Cerebral Ischemic ◽  
Cerebral Ischemic Reperfusion ◽  
And Oxidative Stress

Background: Ischemia/reperfusion (I/R) injury involves complex biological processes and molecular mechanisms such as autophagy. Oxidative stress plays a critical role in the pathogenesis of I/R injury. LncRNAs are the regulatory factor of cerebral I/R injury. Methods: This study constructs cerebral I/R model to investigate role of autophagy and oxidative stress in cerebral I/R injury and the underline regulatory mechanism of SIRT1/ FOXO3a pathway. In this study, lncRNA SNHG12 and FOXO3a expression was up-regulated and SIRT1 expression was down-regulated in HT22 cells of I/R model. Results: Overexpression of lncRNA SNHG12 significantly increased the cell viability and inhibited cerebral ischemicreperfusion injury induced by I/Rthrough inhibition of autophagy. In addition, the transfected p-SIRT1 significantly suppressed the release of LDH and SOD compared with cells co-transfected with SIRT1 and FOXO3a group and cells induced by I/R and transfected with p-SNHG12 group and overexpression of cells co-transfected with SIRT1 and FOXO3 further decreased the I/R induced release of ROS and MDA. Conclusion: In conclusion, lncRNA SNHG12 increased cell activity and inhibited oxidative stress through inhibition of SIRT1/FOXO3a signaling-mediated autophagy in HT22 cells of I/R model. This study might provide new potential therapeutic targets for further investigating the mechanisms in cerebral I/R injury and provide.

The Concomitance of Hypertension and Diabetes Exacerbating Retinopathy: The Role of Inflammation and Oxidative Stress.

2013 ◽  
Vol 8 (4) ◽  
pp. 266-277 ◽  
Author(s):  
Diego Duarte ◽  
Kamila Silva ◽  
Mariana Rosales ◽  
José Lopes de Faria ◽  
Jacqueline Lopes de Faria
Keyword(s):  
Oxidative Stress ◽  
And Oxidative Stress

scholarly journals Molecular Mechanisms of Obesity-Linked Cardiac Dysfunction: An Up-Date on Current Knowledge

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 629
Author(s):  
Jorge Gutiérrez-Cuevas ◽  
Ana Sandoval-Rodriguez ◽  
Alejandra Meza-Rios ◽  
Hugo Christian Monroy-Ramírez ◽  
Marina Galicia-Moreno ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Dysfunction ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Peroxisome Proliferator ◽  
White Adipocyte ◽  
Peroxisome Proliferator Activated Receptors ◽  
And Oxidative Stress

Obesity is defined as excessive body fat accumulation, and worldwide obesity has nearly tripled since 1975. Excess of free fatty acids (FFAs) and triglycerides in obese individuals promote ectopic lipid accumulation in the liver, skeletal muscle tissue, and heart, among others, inducing insulin resistance, hypertension, metabolic syndrome, type 2 diabetes (T2D), atherosclerosis, and cardiovascular disease (CVD). These diseases are promoted by visceral white adipocyte tissue (WAT) dysfunction through an increase in pro-inflammatory adipokines, oxidative stress, activation of the renin-angiotensin-aldosterone system (RAAS), and adverse changes in the gut microbiome. In the heart, obesity and T2D induce changes in substrate utilization, tissue metabolism, oxidative stress, and inflammation, leading to myocardial fibrosis and ultimately cardiac dysfunction. Peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of carbohydrate and lipid metabolism, also improve insulin sensitivity, triglyceride levels, inflammation, and oxidative stress. The purpose of this review is to provide an update on the molecular mechanisms involved in obesity-linked CVD pathophysiology, considering pro-inflammatory cytokines, adipokines, and hormones, as well as the role of oxidative stress, inflammation, and PPARs. In addition, cell lines and animal models, biomarkers, gut microbiota dysbiosis, epigenetic modifications, and current therapeutic treatments in CVD associated with obesity are outlined in this paper.

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