scholarly journals Melatonin Alleviates Cardiac Function in Sepsis-Caused Myocarditis via Maintenance of Mitochondrial Function

2021 ◽  
Vol 8 ◽  
Author(s):  
Liyang Chen ◽  
Qing Tian ◽  
Zhiguang Shi ◽  
Yu Qiu ◽  
Qiulun Lu ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
Messenger Rna ◽  
Cecal Ligation ◽  
Protective Role ◽  
Mrna Levels ◽  
Cardiac Damage ◽  
Cardiac Inflammation ◽  
Mitochondrial Ros ◽  
Cecal Ligation Puncture

Melatonin (N-acetyl-5-methoxytryptamine) has been shown to have a cardioprotective effect against myocarditis. However, the mechanisms underlying the protective role of melatonin (MLT) in sepsis-induced myocarditis are yet to be revealed. In this study, MLT was administrated to mice, 14 days before cecal ligation puncture surgery. Echocardiography results showed that MLT alleviated cardiac dysfunction in sepsis-induced myocarditis. Furthermore, MLT reduced cardiac inflammation by inhibiting the expression of Il-1α, Il-1β, Il-6, and Mcp-1 messenger RNA (mRNA) levels. The RNA sequencing (RNA-seq) assays with heart tissues showed that MLT maintains the mitochondrial function in sepsis-caused myocarditis. Additionally, the production of reactive oxygen species (ROS) in heart tissues was suppressed by MLT. Taken together, in evaluating the therapeutic effect of MLT on sepsis-induced myocarditis, the results showed that MLT alleviated cardiac damage by regulating mitochondrial function and mitochondrial ROS.

scholarly journals Melatonin Alleviates Renal Injury in Mouse Model of Sepsis

2021 ◽  
Vol 12 ◽  
Author(s):  
Liyang Chen ◽  
Zhijian Han ◽  
Zhiguang Shi ◽  
Chao Liu ◽  
Qiulun Lu
Keyword(s):  
Renal Injury ◽  
Oxidant Stress ◽  
Mrna Level ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Protective Role ◽  
Cecal Ligation Puncture ◽  
Species Production

Melatonin (N-acetyl-5-methoxytryptamine; MLT) has been shown to have a renal-protective effect against kidney injury. However, the mechanisms underlying the protective role of MLT in sepsis-induced renal injury are yet to be revealed. In this study, MLT alleviated renal dysfunction with the increase of BUN (blood urea nitrogen) and SCR (serum creatinine) and reduction of fibrosis in the CLP (cecal ligation puncture) model. RNA-seq analysis showed that MLT repressed the oxidant stress in response to kidney injury. Our in vitro study showed that MLT suppresses LPS-induced accumulation of ROS (reactive oxygen species) production via SOD2 downregulation and Nox4 upregulation in HK-2 cells. Furthermore, we found that MLT alleviated the inflammatory response, with the mRNA-level reduction of Il-1α, Il-1β, Mcp-1, and Tgf-β1. Taken together, in evaluating the therapeutic effect of MLT on sepsis-induced acute kidney injury, the results showed that MLT alleviated renal damage by regulating the production of ROS.

scholarly journals Inhibition of the ROS-EGFR Pathway Mediates the Protective Action of Nox1/4 Inhibitor GKT137831 against Hypertensive Cardiac Hypertrophy via Suppressing Cardiac Inflammation and Activation of Akt and ERK1/2

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Si-yu Zeng ◽  
Qiu-jiang Yan ◽  
Li Yang ◽  
Qing-hua Mei ◽  
Hui-qin Lu
Keyword(s):  
Left Ventricle ◽  
Cardiac Hypertrophy ◽  
Protective Action ◽  
Interleukin 1 ◽  
Growth Factor Receptor ◽  
Protective Role ◽  
Mrna Levels ◽  
Cardiac Inflammation ◽  
Egfr Inhibition

Oxidative stress, inflammation, and hypertension constitute a self-perpetuating vicious circle to exacerbate hypertension and subsequent hypertensive cardiac hypertrophy. NADPH oxidase (Nox) 1/4 inhibitor GKT137831 alleviates hypertensive cardiac hypertrophy in models of secondary hypertension; however, it remains unclear about its effect on hypertensive cardiac hypertrophy in models of essential hypertension. This study is aimed at determining the beneficial role of GKT137831 in hypertensive cardiac hypertrophy in spontaneously hypertensive rats (SHRs) and its mechanisms of action. Treating with GKT137831 prevented cardiac hypertrophy in SHRs. Likewise, decreasing production of reactive oxygen species (ROS) with GKT137831 reduced epidermal growth factor receptor (EGFR) activity in the left ventricle of SHRs. Additionally, EGFR inhibition also reduced ROS production in the left ventricle and blunted hypertensive cardiac hypertrophy in SHRs. Moreover, inhibition of the ROS-EGFR pathway with Nox1/4 inhibitor GKT137831 or selective EGFR inhibitor AG1478 reduced protein and mRNA levels of proinflammatory cytokines tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and interleukin 1β (IL-1β), as well as the activities of Akt and extracellular signal-regulated kinase (ERK) 1/2 in the left ventricle of SHRs. In summary, GKT137831 prevents hypertensive cardiac hypertrophy in SHRs, Nox-deprived ROS regulated EGFR activation through positive feedback in the hypertrophic myocardium, and inhibition of the ROS-EGFR pathway mediates the protective role of GKT137831 in hypertensive cardiac hypertrophy via repressing cardiac inflammation and activation of Akt and ERK1/2. This research will provide additional details for GKT137831 to prevent hypertensive cardiac hypertrophy.

scholarly journals Protective role of estrogen against excessive erythrocytosis in Monge’s disease

2021 ◽  
Vol 53 (1) ◽  
pp. 125-135
Author(s):  
Priti Azad ◽  
Francisco C. Villafuerte ◽  
Daniela Bermudez ◽  
Gargi Patel ◽  
Gabriel G. Haddad
Keyword(s):  
High Altitude ◽  
Messenger Rna ◽  
Target Genes ◽  
Protective Role ◽  
Mrna Levels ◽  
Protein Levels ◽  
Hypoxic Conditions ◽  
Andean Population

AbstractMonge’s disease (chronic mountain sickness (CMS)) is a maladaptive condition caused by chronic (years) exposure to high-altitude hypoxia. One of the defining features of CMS is excessive erythrocytosis with extremely high hematocrit levels. In the Andean population, CMS prevalence is vastly different between males and females, being rare in females. Furthermore, there is a sharp increase in CMS incidence in females after menopause. In this study, we assessed the role of sex hormones (testosterone, progesterone, and estrogen) in CMS and non-CMS cells using a well-characterized in vitro erythroid platform. While we found that there was a mild (nonsignificant) increase in RBC production with testosterone, we observed that estrogen, in physiologic concentrations, reduced sharply CD235a+ cells (glycophorin A; a marker of RBC), from 56% in the untreated CMS cells to 10% in the treated CMS cells, in a stage-specific and dose-responsive manner. At the molecular level, we determined that estrogen has a direct effect on GATA1, remarkably decreasing the messenger RNA (mRNA) and protein levels of GATA1 (p < 0.01) and its target genes (Alas2, BclxL, and Epor, p < 0.001). These changes result in a significant increase in apoptosis of erythroid cells. We also demonstrate that estrogen regulates erythropoiesis in CMS patients through estrogen beta signaling and that its inhibition can diminish the effects of estrogen by significantly increasing HIF1, VEGF, and GATA1 mRNA levels. Taken altogether, our results indicate that estrogen has a major impact on the regulation of erythropoiesis, particularly under chronic hypoxic conditions, and has the potential to treat blood diseases, such as high altitude severe erythrocytosis.

scholarly journals A Contemporary View of Natriuretic Peptides in the SARS-CoV-2 Era

2021 ◽  
Vol 12 ◽  
Author(s):  
Speranza Rubattu ◽  
Giovanna Gallo ◽  
Massimo Volpe
Keyword(s):  
Viral Infection ◽  
Natriuretic Peptides ◽  
Pulmonary Inflammation ◽  
Protective Role ◽  
Protective Effects ◽  
Cardiac Damage ◽  
Protective Function ◽  
Therapeutic Benefits ◽  
Prognostic Implications

The heart releases natriuretic peptides (NPs) which represent an important hormonal axis with cardiorenal protective effects. In view of their properties, NPs have pathophysiologic, diagnostic and prognostic implications in several cardiovascular diseases (CVDs). Severe pulmonary inflammation, as induced by the SARS-COV2, may increase pulmonary pressure with potential influence on NPs release, whereby normal cardiovascular integrity becomes impaired. Moreover, pre-existing CVDs are strong negative prognostic factors since they exacerbate the effects of the viral infection and lead to worse outcomes. In this context, it may be expected that NPs exert a key protective role toward the virus infection whereas an impairment of NPs release contributes to the virus deleterious effects. In this review article we explore the potential involvement of NPs in the COVID-19 disease. To this aim, we will first focus on the interactions between NPs and the Ang II/ATIR arm of the renin-angiotensin-aldosterone system (RAAS) as well as with the protective ACE2/Ang (1-7) arm of the RAAS. Subsequently, we will review evidence that strongly supports the role of increased NT-proBNP level as a marker of cardiac damage and of worse prognosis in the COVID-19 affected patients. Finally, we will discuss the potential therapeutic benefits of these protective hormones toward the viral infection through their endothelial protective function, anti-inflammatory and anti-thrombotic effects. In conclusion, the potential implications of NPs in the SARS-CoV-2 infection, as discussed in our article, represent an important issue that deserves to be fully investigated.

scholarly journals Protective Effects of Anti-depressant Citalopram Against Abnormal APP Processing and Amyloid Beta-induced Mitochondrial Dynamics, Biogenesis, Mitophagy and Synaptic Toxicities in Alzheimer’s Disease

2021 ◽  
Author(s):  
Arubala P Reddy ◽  
Xiangling Yin ◽  
Neha Sawant ◽  
P Hemachandra Reddy
Keyword(s):  
Electron Microscopy ◽  
Alzheimer’S Disease ◽  
Transmission Electron Microscopy ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Protective Role ◽  
Mrna Levels ◽  
Ht22 Cells ◽  
Transmission Electron

Abstract The purpose of this study is to study the neuroprotective role of selective serotonin reuptake inhibitor (SSRI), citalopram against Alzheimer’s disease (ad). Multiple SSRIs, including citalopram are reported to treat patients with depression, anxiety, and ad. However, their protective cellular mechanisms have not been studied completely. In the current study, we investigated the protective role of citalopram against impaired mitochondrial dynamics, defective mitochondrial biogenesis, defective mitophagy, and synaptic dysfunction in immortalized mouse primary hippocampal cells (HT22) expressing mutant APP (SWI/IND) mutations. Using quantitative RT-PCR, immunoblotting, biochemical methods and transmission electron microscopy methods, we assessed mutant full-length APP/C-terminal fragments and Aβ levels and mRNA and protein levels of mitochondrial dynamics, biogenesis, mitophagy, and synaptic genes in mAPP-HT22 cells and mAPP-HT22 cells treated with citalopram. Increased levels of mRNA levels of mitochondrial fission genes, decreased levels of fusion biogenesis, autophagy, mitophagy and synaptic genes were found in mAPP-HT22 cells relative to WT-HT22 cells. However, in mAPP-HT22 cells treated with citalopram compared to mAPP-HT22 cells, revealed reduced levels of the mitochondrial fission genes, increased fusion, biogenesis, autophagy, mitophagy, and synaptic genes. Our protein data agrees with mRNA levels. Transmission electron microscopy revealed significantly increased mitochondrial numbers and reduced mitochondrial length in mAPP-HT22 cells; these were reversed in citalopram treated mAPP-HT22 cells. Cell survival rates were increased in citalopram treated mAPP-HT22 relative to citalopram-untreated mAPP-HT22. Further, mAPP and C-terminal fragments were also reduced in citalopram treated cells. These findings suggest that citalopram reduces mutant APP and Aβ and mitochondrial toxicities and may have a protective role of mutant APP and Aβ-induced injuries in patients with depression, anxiety, and ad.

scholarly journals Methylation and Gene Expression of BCAT1 and IKZF1 in Colorectal Cancer Tissues

2018 ◽  
Vol 12 ◽  
pp. 117955491877506 ◽  
Author(s):  
Maher Jedi ◽  
Graeme P Young ◽  
Susanne K Pedersen ◽  
Erin L Symonds
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Messenger Rna ◽  
Stage Iv ◽  
Mrna Levels ◽  
Polymerase Chain ◽  
Cancer Tissues ◽  
The Relationship ◽  
Neoplastic Tissues

The genes BCAT1 and IKZF1 are hypermethylated in colorectal cancer (CRC), but little is known about how this relates to gene expression. This study assessed the relationship between methylation and gene expression of BCAT1 and IKZF1 in CRC and adjacent non-neoplastic tissues. The tissues were obtained at surgery from 36 patients diagnosed with different stages of CRC (stage I n = 8, stage II n = 13, stage III n = 10, stage IV n = 5). Methylated BCAT1 and IKZF1 were detected in 92% and 72% CRC tissues, respectively, with levels independent of stage ( P > .05). In contrast, only 31% and 3% of non-neoplastic tissues were methylated for BCAT1 and IKZF1, respectively ( P < .001). The IKZF1 messenger RNA (mRNA) expression was significantly lower in the cancer tissues compared with that of non-neoplastic tissues, whereas the BCAT1 mRNA levels were similar. The latter may be due to the BCAT1 polymerase chain reaction assay detecting more than 1 mRNA transcript. Further studies are warranted to establish the role of the epigenetic silencing of IKZF1 in colorectal oncogenesis.

The protective role of neocuproine against cardiac damage in isolated perfused rat hearts

1990 ◽  
Vol 8 (2) ◽  
pp. 133-143 ◽  
Author(s):  
Yori J. Appelbaum ◽  
Jeffrey Kuvin ◽  
Joseph B. Borman ◽  
Gideon Uretzky ◽  
Mordechai Chevion
Keyword(s):  
Protective Role ◽  
Cardiac Damage ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
Isolated Perfused Rat Hearts

scholarly journals Irisin Improves Autophagy of Aged Hepatocytes via Increasing Telomerase Activity in Liver Injury

2020 ◽  
Vol 2020 ◽  
pp. 1-13 ◽  
Author(s):  
Jianbin Bi ◽  
Lifei Yang ◽  
Tao Wang ◽  
Jia Zhang ◽  
Teng Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Mitochondrial Function ◽  
Ischemia Reperfusion ◽  
The Elderly ◽  
Telomerase Activity ◽  
Protective Role ◽  
Primary Hepatocytes ◽  
Old Rats

An aged liver has decreased reparative capacity during ischemia-reperfusion (IR) injury. A recent study showed that plasma irisin levels predict telomere length in healthy adults. The aim of the present study is to clarify the role of irisin, telomerase activity, and autophagy during hepatic IR in the elderly. To study this, hepatic IR was established in 22-month- and 3-month-old rats and primary hepatocytes were isolated. The results showed that the old rats exhibited more serious liver injury and lower levels of irisin expression, telomerase activity, autophagy ability, and mitochondrial function than young rats during hepatic IR. Irisin activated autophagy and improved mitochondrial function via increasing telomerase activity in aged hepatocytes. Inhibition of telomerase activity by BIBP1532 abolished the protective role of irisin in hepatocytes during hypoxia and reoxygenation. Additionally, this study proved irisin increased the telomerase activity via inhibition of the phosphorylation of JNK during hepatic IR. Administration of exogenous irisin significantly mitigated the inflammation, oxidative stress, apoptosis, and liver injury in an old rat model of hepatic IR. In conclusion, irisin improves autophagy of aged hepatocytes via increasing telomerase activity in hepatic IR. Irisin exhibits conspicuous benefits in increasing reparative capacity of an aged liver during hepatic IR.

Naringenin improves mitochondrial function and reduces cardiac damage following ischemia-reperfusion injury: the role of the AMPK-SIRT3 signaling pathway

2019 ◽  
Vol 10 (5) ◽  
pp. 2752-2765 ◽  
Author(s):  
Li-Ming Yu ◽  
Xue Dong ◽  
Xiao-Dong Xue ◽  
Jian Zhang ◽  
Zhi Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reperfusion Injury ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Function ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cardiac Damage ◽  
Mitochondrial Oxidative Stress ◽  
Stress Damage

Naringenin directly inhibits mitochondrial oxidative stress damage and preserves mitochondrial biogenesisviaAMPK-SIRT3 signaling, thus attenuating MI/R injury.

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