scholarly journals miR-103 Regulates Oxidative Stress by Targeting the BCL2/Adenovirus E1B 19 kDa Interacting Protein 3 in HUVECs

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Mao-Chun Xu ◽  
Xiu-Fang Gao ◽  
Changwu Ruan ◽  
Zhi-Ru Ge ◽  
Ji-De Lu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Critical Role ◽  
Cell Activity ◽  
Antioxidant Effect ◽  
Dependent Manner ◽  
Ros Production ◽  
Interacting Protein ◽  
Adenovirus E1b ◽  
Antioxidative Therapy ◽  
First Time

Oxidative stress plays a critical role in cardiovascular diseases. Salidroside, a glycoside fromRhodiola rosea, has been used as an antioxidative therapy for oxidative injury in cardiac diseases. However, the mechanism underlying its antioxidant effect needs to be elucidated. Treatment of HUVECs with H2O2significantly decreased the expression of miR-103 in a dose- and time-dependent manner, whereas pretreatment with salidroside significantly inhibited this decrease. Subsequent analysis showed that overexpression of miR-103 abrogated cell activity and ROS production induced by H2O2. Bcl2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) was determined to be a novel miR-103 target in HUVECs. Interestingly, H2O2treatment upregulated BNIP3 expression; in turn, this effect was inhibited by pretreatment with salidroside. Further studies confirmed that the knockdown of BNIP3 enhanced cell activity and suppressed the ROS production induced by H2O2. These results demonstrated for the first time that salidroside protects HUVECs in part by upregulating the expression of miR-103, which mediates BNIP3 downregulation and plays an important role in the cytoprotective actions.

scholarly journals MicroRNA-103 Protects Coronary Artery Endothelial Cells against H2O2-Induced Oxidative Stress via BNIP3-Mediated End-Stage Autophagy and Antipyroptosis Pathways

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Yiran Wang ◽  
Xianjing Song ◽  
Zhibo Li ◽  
Ning Liu ◽  
Youyou Yan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Western Blot ◽  
Cell Damage ◽  
Cell Activity ◽  
Specific Effect ◽  
Interacting Protein ◽  
Adenovirus E1b ◽  
End Stage ◽  
Stimulation Of

Endothelial cell damage caused by oxidative stress is widely considered to be a triggering event in atherosclerosis (AS). However, the specific effect elicited by autophagy in endothelial cells undergoing oxidative stress remains controversial, especially during end-stage autophagy. The inhibition of end-stage autophagy has been reported to increase cell pyroptosis and contribute to endothelial damage. Several studies have shown that microRNA-103 is involved in end-stage autophagy; however, its specific mechanism of action is not yet characterized. In this study, we addressed the regulatory role of miR-103 in autophagy during oxidative stress of endothelial cells. Hydrogen peroxide (H2O2) treatment was used as an in vitro model of oxidative stress. MTS and ROS levels were measured to evaluate cell activity. qRT-PCR was used to detect the expression of miR-103. Autophagy was examined using western blot, immunofluorescence staining, and electron microscopy, while western blot analysis detected pyroptosis-related proteins. Results show that miR-103 expression decreased under oxidative stress. Further, miR-103 repressed transcription of Bcl-2/adenovirus E1B 19 kDa interacting protein (BNIP3). The oxidative stress caused by H2O2 caused cell damage from 2 hours (P<0.05) and increased the level of intracellular reactive oxygen species (P<0.05); at the same time, the damage could be further aggravated by the stimulation of bafA1 (P<0.05). Under the stimulation of H2O2, the expression of miR-103 decreased (P<0.05). However, high expression of miR-103 could reduce the accumulation of LC3II and P62 (P<0.05) by inhibiting the downstream target gene Bcl-2/adenovirus E1B 19 kDa interacting protein (BNIP3), thus reducing the occurrence of cell pyroptosis (P<0.05). This process could be blocked by end-stage autophagy inhibitor bafA1 (P<0.05), which further indicated that miR-103 affected cell injury by autophagy. On the contrary, the low expression of miR-103 promoted the accumulation of autophagy protein and increased the occurrence of pyroptosis (P<0.05). In conclusion, inhibition of miR-103 restrained end-stage of autophagy by regulating BNIP3, thus changing the occurrence of cell pyroptosis.

Adrenomedullin inhibits angiotensin II-induced oxidative stress via Csk-mediated inhibition of Src activity

2007 ◽  
Vol 292 (4) ◽  
pp. H1714-H1721 ◽  
Author(s):  
Jing Liu ◽  
Tatsuo Shimosawa ◽  
Hiromitsu Matsui ◽  
Fanyin Meng ◽  
Scott C. Supowit ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Ii ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Ros Production ◽  
Ang Ii ◽  
Concentration Dependent Manner ◽  
Cardiovascular Damage ◽  
Cgrp Receptor Antagonist ◽  
First Time

We have demonstrated that adrenomedullin (AM) protects against angiotensin II (ANG II)-induced cardiovascular damage through the attenuation of increased oxidative stress observed in AM-deficient mice. However, the mechanism(s) that underlie this activity remain unclear. To address this question, we investigated the effect of AM on ANG II-stimulated reactive oxygen species (ROS) production in cultured rat aortic vascular smooth muscle cells (VSMCs). ANG II markedly increased ROS production through activation of NADPH oxidase. This effect was significantly attenuated by AM in a concentration-dependent manner. This effect was mimicked by dibutyl-cAMP and blocked by pretreatment with N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide hydrochloride (H-89), a protein kinase A inhibitor, and CGRP8–37, an AM/CGRP receptor antagonist. This inhibitory effect of AM was also lost following the expression of a constitutively active Src. Moreover, AM intersected ANG II signaling by inducing COOH-terminal Src kinase (Csk) activation that, in turn, inhibits Src activation. These data, for the first time, demonstrate that AM attenuates the ANG II-induced increase in ROS in VSMCs via activation of Csk, thereby inhibiting Src activity.

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.

scholarly journals Heme induces programmed necrosis on macrophages through autocrine TNF and ROS production

Blood ◽  
2012 ◽  
Vol 119 (10) ◽  
pp. 2368-2375 ◽  
Author(s):  
Guilherme B. Fortes ◽  
Leticia S. Alves ◽  
Rosane de Oliveira ◽  
Fabianno F. Dutra ◽  
Danielle Rodrigues ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Critical Role ◽  
Membrane Integrity ◽  
Iron Chelation ◽  
Heme Oxygenase 1 ◽  
Cytotoxic Effects ◽  
Interacting Protein ◽  
Free Heme ◽  
Necrosis Factor

Abstract Diseases that cause hemolysis or myonecrosis lead to the leakage of large amounts of heme proteins. Free heme has proinflammatory and cytotoxic effects. Heme induces TLR4-dependent production of tumor necrosis factor (TNF), whereas heme cytotoxicity has been attributed to its ability to intercalate into cell membranes and cause oxidative stress. We show that heme caused early macrophage death characterized by the loss of plasma membrane integrity and morphologic features resembling necrosis. Heme-induced cell death required TNFR1 and TLR4/MyD88-dependent TNF production. Addition of TNF to Tlr4−/− or to Myd88−/− macrophages restored heme-induced cell death. The use of necrostatin-1, a selective inhibitor of receptor-interacting protein 1 (RIP1, also known as RIPK1), or cells deficient in Rip1 or Rip3 revealed a critical role for RIP proteins in heme-induced cell death. Serum, antioxidants, iron chelation, or inhibition of c-Jun N-terminal kinase (JNK) ameliorated heme-induced oxidative burst and blocked macrophage cell death. Macrophages from heme oxygenase-1 deficient mice (Hmox1−/−) had increased oxidative stress and were more sensitive to heme. Taken together, these results revealed that heme induces macrophage necrosis through 2 synergistic mechanisms: TLR4/Myd88-dependent expression of TNF and TLR4-independent generation of ROS.

scholarly journals Cyclic AMP-dependent Protein Lysine Acylation in Mycobacteria Regulates Fatty Acid and Propionate Metabolism

2013 ◽  
Vol 288 (20) ◽  
pp. 14114-14124 ◽  
Author(s):  
Subhalaxmi Nambi ◽  
Kallol Gupta ◽  
Moitrayee Bhattacharyya ◽  
Parvathy Ramakrishnan ◽  
Vaishnavi Ravikumar ◽  
...  
Keyword(s):  
Critical Role ◽  
Fatty Acyl ◽  
Intracellular Camp ◽  
Dependent Manner ◽  
Multiple Substrates ◽  
Propionate Metabolism ◽  
Lysine Residues ◽  
Dependent Protein ◽  
First Time ◽  
Camp Levels

Acetylation of lysine residues is a posttranslational modification that is used by both eukaryotes and prokaryotes to regulate a variety of biological processes. Here we identify multiple substrates for the cAMP-dependent protein lysine acetyltransferase from Mycobacterium tuberculosis (KATmt). We demonstrate that a catalytically important lysine residue in a number of FadD (fatty acyl CoA synthetase) enzymes is acetylated by KATmt in a cAMP-dependent manner and that acetylation inhibits the activity of FadD enzymes. A sirtuin-like enzyme can deacetylate multiple FadDs, thus completing the regulatory cycle. Using a strain deleted for the KATmt ortholog in Mycobacterium bovis Bacillus Calmette-Guérin (BCG), we show for the first time that acetylation is dependent on intracellular cAMP levels. KATmt can utilize propionyl CoA as a substrate and, therefore, plays a critical role in alleviating propionyl CoA toxicity in mycobacteria by inactivating acyl CoA synthetase (ACS). The precision by which mycobacteria can regulate the metabolism of fatty acids in a cAMP-dependent manner appears to be unparalleled in other biological organisms and is ideally suited to adapt to the complex environment that pathogenic mycobacteria experience in the host.

scholarly journals Bnip3 and AIF cooperate to induce apoptosis and cavitation during epithelial morphogenesis

2012 ◽  
Vol 198 (1) ◽  
pp. 103-114 ◽  
Author(s):  
Yanmei Qi ◽  
Xiaoxiang Tian ◽  
Jie Liu ◽  
Yaling Han ◽  
Alan M. Graham ◽  
...  
Keyword(s):  
Protein A ◽  
Hypoxia Inducible Factor ◽  
Embryonic Stem ◽  
Embryoid Bodies ◽  
Epithelial Morphogenesis ◽  
Dependent Manner ◽  
Interacting Protein ◽  
The Core ◽  
Adenovirus E1b ◽  
Induced Apoptosis

Apoptosis is an essential step in cavitation during embryonic epithelial morphogenesis, but its mechanisms are largely unknown. In this paper, we used embryonic stem cell–differentiated embryoid bodies (EBs) as a model and found that Bnip3 (Bcl-2/adenovirus E1B 19-kD interacting protein), a BH3-only proapoptotic protein, was highly up-regulated during cavitation in a hypoxia-dependent manner. Short hairpin RNA silencing of Bnip3 inhibited apoptosis of the core cells and delayed cavitation. We show that the Bnip3 up-regulation was mediated mainly by hypoxia-inducible factor (HIF)–2. Ablation of HIF-2α or HIF-1β, the common β subunit of HIF-1 and -2, suppressed Bnip3 up-regulation and inhibited apoptosis and cavitation. We further show that apoptosis-inducing factor (AIF) cooperated with Bnip3 to promote lumen clearance. Bnip3 silencing in AIF-null EBs nearly blocked apoptosis and cavitation. Moreover, AIF also regulated Bnip3 expression through mitochondrial production of reactive oxygen species and consequent HIF-2α stabilization. These results uncover a mechanism of cavitation through hypoxia-induced apoptosis of the core cells mediated by HIFs, Bnip3, and AIF.

scholarly journals Diabetes induces and calcium channel blockers prevent cardiac expression of proapoptotic thioredoxin-interacting protein

2009 ◽  
Vol 296 (5) ◽  
pp. E1133-E1139 ◽  
Author(s):  
Junqin Chen ◽  
Hyunjoo Cha-Molstad ◽  
Anna Szabo ◽  
Anath Shalev
Keyword(s):  
Calcium Channel ◽  
Diabetic Cardiomyopathy ◽  
Calcium Channel Blockers ◽  
Caspase 3 ◽  
Critical Role ◽  
Cardiomyocyte Apoptosis ◽  
Channel Blockers ◽  
Dependent Manner ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein

Cardiomyocyte apoptosis is a critical process in the pathogenesis of ischemic and diabetic cardiomyopathy, but the mechanisms are not fully understood. Thioredoxin-interacting protein (TXNIP) has recently been shown to have deleterious effects in the cardiovascular system and we therefore investigated whether it may also play a role in diabetes-associated cardiomyocyte apoptosis. In fact, TXNIP expression was increased in H9C2 cardiomyocytes incubated at high glucose, and cardiac expression of TXNIP and cleaved caspase-3 were also elevated in vivo in streptozotocin- and obesity-induced diabetic mice. Together, these findings not only suggest that TXNIP is involved in diabetic cardiomyopathy but also that it may represent a novel therapeutic target. Surprisingly, testing putative TXNIP modulators revealed that calcium channel blockers reduce cardiomyocyte TXNIP transcription and protein levels in a dose-dependent manner. Oral administration of verapamil for 3 wk also reduced cardiac TXNIP expression in mice even in the face of severe diabetes, and these reduced TXNIP levels were associated with decreased apoptosis. To determine whether lack of TXNIP can mimic the verapamil-induced decrease in apoptosis, we used TXNIP-deficient HcB-19 mice, harboring a natural nonsense mutation in the TXNIP gene. Interestingly, we found significantly reduced cleaved caspase-3 levels in HcB-19 hearts, suggesting that TXNIP plays a critical role in cardiac apoptosis and that the verapamil effects were mediated by TXNIP reduction. Thus our results suggest that TXNIP reduction is a powerful target to enhance cardiomyocyte survival and that agents such as calcium channel blockers may be useful in trying to achieve this goal and prevent diabetic cardiomyopathy.

scholarly journals Gi proteins mediate activation of the canonical hedgehog pathway in the myocardium

2014 ◽  
Vol 307 (1) ◽  
pp. H66-H72 ◽  
Author(s):  
Christian J. Carbe ◽  
Lan Cheng ◽  
Sankar Addya ◽  
Jessica I. Gold ◽  
Erhe Gao ◽  
...  
Keyword(s):  
Purinergic Signaling ◽  
Transmembrane Protein ◽  
Critical Role ◽  
Transcriptional Response ◽  
Neonatal Rat ◽  
Small Subset ◽  
Dependent Manner ◽  
Gli1 Expression ◽  
Ventricular Cardiomyocytes ◽  
First Time

During myocardial ischemia, upregulation of the hedgehog (Hh) pathway promotes neovascularization and increases cardiomyocyte survival. The canonical Hh pathway activates a transcriptional program through the Gli family of transcription factors by derepression of the seven-transmembrane protein smoothened (Smo). The mechanisms linking Smo to Gli are complex and, in some cell types, involve coupling of Smo to Gi proteins. In the present study, we investigated, for the first time, the transcriptional response of cardiomyocytes to sonic hedgehog (Shh) and the role of Gi protein utilization. Our results show that Shh strongly activates Gli1 expression by quantitative PCR in a Smo-dependent manner in neonatal rat ventricular cardiomyocytes. Microarray analysis of gene expression changes elicited by Shh and sensitive to a Smo inhibitor identified a small subset of 37 cardiomyocyte-specific genes regulated by Shh, including some in the PKA and purinergic signaling pathways. In addition, neonatal rat ventricular cardiomyocytes infected with an adenovirus encoding GiCT, a peptide that impairs receptor-Gi protein coupling, showed reduced activation of Hh targets. In vitro data were confirmed in transgenic mice with cardiomyocyte-inducible GiCT expression. Transgenic GiCT mice showed specific reduction of Gli1 expression in the heart under basal conditions and failed to upregulate the Hh pathway upon ischemia and reperfusion injury, unlike their littermate controls. This study characterizes, for the first time, the transcriptional response of cardiomyocytes to Shh and establishes a critical role for Smo coupling to Gi in Hh signaling in the normal and ischemic myocardium.

scholarly journals Antioxidant and Anti-inflammatory Protective Properties of Thai Shallot (Allium ascalonicum cv. Chiangmai) Juice on Human Vascular Endothelial Cell Lines (EA.hy926)

2019 ◽  
Vol 16 (3) ◽  
pp. 175-184
Author(s):  
Sakaewan OUNJAIJEAN ◽  
Sukanya CHACHIYO ◽  
Kanokwan KULPRACHAKARN ◽  
Kongsak BOONYAPRANAI ◽  
Somdet SRICHAIRATANAKOOL ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cell ◽  
Vascular Endothelial Cell ◽  
Membrane Lipid ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Ros Production ◽  
Food Ingredient ◽  
Human Vascular Endothelial Cell ◽  
Anti Inflammatory

Oxidative stress and inflammation are 2 major contributors to numerous life-threatening disorders, including vascular pathologies. Shallots (Allium ascalonicum) are a type of red onion which grows in Southeast Asia. Bulbs of this plant are used both as a food ingredient and in traditional medicine. This study attempted to investigate the possible ways that juice extracted from Thai shallot (A.ascalonicum cv. Chiangmai) bulbs could be used in the prevention of cardiovascular complications. The antioxidative and anti-inflammatory effects of shallot juice extract (SHE) on human vascular endothelial cells (EA.hy926) were investigated. Cell viability was evaluated by MTT assay, membrane lipid peroxidation by thiobarbituric acid reactive substances assay, intracellular reactive oxygen species (ROS) production by the fluorescent probe 6-carboxy-2'-7'-dichlorofluoresceine, and interleukin-6 (IL-6) released by ELISA. The shallot juice showed extremely low cytotoxicity against EA.hy926 cells, with IC50 of 41.9 and 27.3 mg/ml for 24 h- and 48 h-incubation, respectively. SHE reduced the iron-induced malondialdehyde production in a dose-dependent manner. The extract also demonstrated antioxidant activity as shown by a significant reduction of H2O2-induced ROS production at a low concentration (< 200 mg/ml). Furthermore, SHE significantly attenuated the level of IL-6 released during lipopolysaccharide stimulation (p < 0.05). It is of interest that the juice extracted from Thai shallot bulbs demonstrated both cellular antioxidant and anti-inflammatory properties in endothelial cell models, combined with a reduction in toxicity. Shallot extract could be considered as a nutraceutical for the prevention or management of vascular diseases as it is related to oxidative stress and inflammation.

scholarly journals Molecular Aspects of Colorectal Adenomas: The Interplay among Microenvironment, Oxidative Stress, and Predisposition

2020 ◽  
Vol 2020 ◽  
pp. 1-19 ◽  
Author(s):  
Gitana Maria Aceto ◽  
Teresa Catalano ◽  
Maria Cristina Curia
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Excision Repair ◽  
Critical Role ◽  
Chemotherapeutic Agents ◽  
Colorectal Adenomas ◽  
Endoscopic Polypectomy ◽  
Advanced Tumor Stage ◽  
Ros Production ◽  
Advanced Tumor

The development of colorectal cancer (CRC) is a multistep process initiated by a benign polyp that has the potential to evolve into in situ carcinoma through the interactions between environmental and genetic factors. CRC incidence rates are constantly increased for young adult patients presenting an advanced tumor stage. The majority of CRCs arise from colonic adenomas originating from aberrant cell proliferation of colon epithelium. Endoscopic polypectomy represents a tool for early detection and removal of polyps, although the occurrence of cancers after negative colonoscopy shows a significant incidence. It has long been recognized that the aberrant regulation of Wingless/It (Wnt)/β-Catenin signaling in the pathogenesis of colorectal cancer is supported by its critical role in the differentiation of stem cells in intestinal crypts and in the maintenance of intestinal homeostasis. For this review, we will focus on the development of adenomatous polyps through the interplay between renewal signaling in the colon epithelium and reactive oxygen species (ROS) production. The current knowledge of molecular pathology allows us to deepen the relationships between oxidative stress and other risk factors as lifestyle, microbiota, and predisposition. We underline that the chronic inflammation and ROS production in the colon epithelium can impair the Wnt/β-catenin and/or base excision repair (BER) pathways and predispose to polyp development. In fact, the coexistence of oxidative DNA damage and errors in DNA polymerase can foster C>T transitions in various types of cancer and adenomas, leading to a hypermutated phenotype of tumor cells. Moreover, the function of Adenomatous Polyposis Coli (APC) protein in regulating DNA repair is very important as therapeutic implication making DNA damaging chemotherapeutic agents more effective in CRC cells that tend to accumulate mutations. Additional studies will determine whether approaches based on Wnt inhibition would provide long-term therapeutic value in CRC, but it is clear that APC disruption plays a central role in driving and maintaining tumorigenesis.

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