scholarly journals BTK Promotes Atherosclerosis by Regulating Oxidative Stress, Mitochondrial Injury, and ER Stress of Macrophages

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Junxiong Qiu ◽  
Yuan Fu ◽  
Zhiteng Chen ◽  
Lisui Zhang ◽  
Ling Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Er Stress ◽  
Inflammatory Responses ◽  
Cerebrovascular Diseases ◽  
Aseptic Inflammation ◽  
Mitochondrial Injury ◽  
M1 Polarization ◽  
Stress Oxidative ◽  
Signaling Activation

Atherosclerosis (AS) is a chronic metabolic disease in arterial walls, characterized by lipid deposition and persistent aseptic inflammation. AS is regarded as the basis of a variety of cardiovascular and cerebrovascular diseases. It is widely acknowledged that macrophages would become foam cells after internalizing lipoprotein particles, which is an initial factor in atherogenesis. Here, we showed the influences of Bruton’s tyrosine kinase (BTK) in macrophage-mediated AS and how BTK regulates the inflammatory responses of macrophages in AS. Our bioinformatic results suggested that BTK was a potential hub gene, which is closely related to oxidative stress, ER stress, and inflammation in macrophage-induced AS. Moreover, we found that BTK knockdown could restrain ox-LDL-induced NK-κB signaling activation in macrophages and repressed M1 polarization. The mechanistic studies revealed that oxidative stress, mitochondrial injury, and ER stress in macrophages were also suppressed by BTK knockdown. Furthermore, we found that sh-BTK adenovirus injection could alleviate the severity of AS in ApoE-/- mice induced by a high-fat diet in vivo. Our study suggested that BTK promoted ox-LDL-induced ER stress, oxidative stress, and inflammatory responses in macrophages, and it may be a potential therapeutic target in AS.

scholarly journals NADPH oxidase links endoplasmic reticulum stress, oxidative stress, and PKR activation to induce apoptosis

2010 ◽  
Vol 191 (6) ◽  
pp. 1113-1125 ◽  
Author(s):  
Gang Li ◽  
Christopher Scull ◽  
Lale Ozcan ◽  
Ira Tabas
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Cellular Mechanisms ◽  
Apoptosis Pathway ◽  
Stress Oxidative ◽  
Induced Apoptosis ◽  
And Oxidative Stress

Endoplasmic reticulum (ER)–induced apoptosis and oxidative stress contribute to several chronic disease processes, yet molecular and cellular mechanisms linking ER stress and oxidative stress in the setting of apoptosis are poorly understood and infrequently explored in vivo. In this paper, we focus on a previously elucidated ER stress–apoptosis pathway whose molecular components have been identified and documented to cause apoptosis in vivo. We now show that nicotinamide adenine dinucleotide phosphate reduced oxidase (NOX) and NOX-mediated oxidative stress are induced by this pathway and that apoptosis is blocked by both genetic deletion of the NOX subunit NOX2 and by the antioxidant N-acetylcysteine. Unexpectedly, NOX and oxidative stress further amplify CCAAT/enhancer binding protein homologous protein (CHOP) induction through activation of the double-stranded RNA–dependent protein kinase (PKR). In vivo, NOX2 deficiency protects ER-stressed mice from renal cell CHOP induction and apoptosis and prevents renal dysfunction. These data provide new insight into how ER stress, oxidative stress, and PKR activation can be integrated to induce apoptosis in a pathophysiologically relevant manner.

scholarly journals Coptisine Attenuates Diabetes—Associated Endothelial Dysfunction through Inhibition of Endoplasmic Reticulum Stress and Oxidative Stress

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4210
Author(s):  
Yan Zhou ◽  
Chunxiu Zhou ◽  
Xutao Zhang ◽  
Chi Teng Vong ◽  
Yitao Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Risk Factors ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Vascular Function ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Diabetic Mice ◽  
And Oxidative Stress

Coptisine is the major bioactive protoberberine alkaloid found in Rhizoma Coptidis. Coptisine reduces inflammatory responses and improves glucose tolerance; nevertheless, whether coptisine has vasoprotective effect in diabetes is not fully characterized. Conduit arteries including aortas and carotid arteries were obtained from male C57BL/6J mice for ex vivo treatment with risk factors (high glucose or tunicamycin) and coptisine. Some arterial rings were obtained from diabetic mice, which were induced by high-fat diet (45% kcal% fat) feeding for 6 weeks combined with a low-dose intraperitoneal injection of streptozotocin (120 mg/kg). Functional studies showed that coptisine protected endothelium-dependent relaxation in aortas against risk factors and from diabetic mice. Coptisine increased phosphorylations of AMPK and eNOS and downregulated the endoplasmic reticulum (ER) stress markers as determined by Western blotting. Coptisine elevates NO bioavailability and decreases reactive oxygen species level. The results indicate that coptisine improves vascular function in diabetes through suppression of ER stress and oxidative stress, implying the therapeutic potential of coptisine to treat diabetic vasculopathy.

scholarly journals Enhancing the Nrf2 Antioxidant Signaling Provides Protection Against Trichloroethene-mediated Inflammation and Autoimmune Response

2020 ◽  
Vol 175 (1) ◽  
pp. 64-74 ◽  
Author(s):  
Nivedita Banerjee ◽  
Hui Wang ◽  
Gangduo Wang ◽  
M Firoze Khan
Keyword(s):  
Oxidative Stress ◽  
T Cells ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Autoimmune Response ◽  
Mediated Effects ◽  
Antioxidant Gene Expression ◽  
Responsive Element

Abstract Trichloroethene (trichloroethylene, TCE) and one of its reactive metabolites dichloroacetyl chloride (DCAC) are associated with the induction of autoimmunity in MRL+/+ mice. Although oxidative stress plays a major role in TCE-/DCAC-mediated autoimmunity, the underlying molecular mechanisms still need to be delineated. Nuclear factor (erythroid-derived 2)-like2 (Nrf2) is an oxidative stress-responsive transcription factor that binds to antioxidant responsive element (ARE) and provides protection by regulating cytoprotective and antioxidant gene expression. However, the potential of Nrf2 in the regulation of TCE-/DCAC-mediated autoimmunity is not known. This study thus focused on establishing the role of Nrf2 and consequent inflammatory responses in TCE-/DCAC-mediated autoimmunity. To achieve this, we pretreated Kupffer cells (KCs) or T cells with/without tert-butylhydroquinone (tBHQ) followed by treatment with DCAC. In both KCs and T cells, DCAC treatment significantly downregulated Nrf2 and HO-1 expression along with induction of Keap-1 and caspase-3, NF-κB (p65), TNF-α, and iNOS, whereas pretreatment of these cells with tBHQ attenuated these responses. The in vitro findings were further verified in vivo by treating female MRL+/+ mice with TCE along with/without sulforaphane. TCE exposure in mice also led to reduction in Nrf2 and HO-1 but increased phospho-NF-κB (p-p65) and iNOS along with increased anti-dsDNA antibodies. Interestingly, sulforaphane treatment led to amelioration of TCE-mediated effects, resulting in Nrf2 activation and reduction in inflammatory and autoimmune responses. Our results show that TCE/DCAC mediates an impairment in Nrf2 regulation. Attenuation of TCE-mediated autoimmunity via activation of Nrf2 supports that antioxidants sulforaphane/tBHQ could be potential therapeutic agents for autoimmune diseases.

Oxidative stress in primary culture hepatocytes isolated from partially hepatectomized rats

2007 ◽  
Vol 85 (10) ◽  
pp. 1047-1051 ◽  
Author(s):  
Daniel Francés ◽  
M. Teresa Ronco ◽  
Elena Ochoa ◽  
M. Luján Alvarez ◽  
Ariel Quiroga ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Primary Culture ◽  
Cell Injury ◽  
Cultured Cells ◽  
Male Wistar Rats ◽  
Metabolic Activities ◽  
Stress Oxidative ◽  
Species Production

The aim of this study was to evaluate the influence of partial hepatectomy prior to cell isolation on hepatocytes in vitro. We characterized the possible changes of various stress oxidative parameters within the first 24 h after seeding. Male Wistar rats served as donors. Hepatocytes were isolated by collagenase digestion from either liver of simulated surgery (SH) or from liver 1 h after 70% hepatectomy (PH), and the changes in stress parameters were analyzed after 1, 3, 18, and 24 h in culture. At 24 h, only hepatocytes from PH maintained significantly increased reactive oxygen species production, oxidized glutathione percentage, and Cu/Zn superoxide dismutase and catalase activities. Our results show that hepatocytes suffer significant cell injury as a result of the isolation procedure, but primary cultured cells from SH metabolically recover from this stress after 18 h. After this time, primary culture hepatocytes primed by PH maintain their in vivo-like metabolic activities (increase in both oxidative stress and antioxidant status).

scholarly journals In Vivo Anti-Inflammation Potential of Aster koraiensis Extract for Dry Eye Syndrome by the Protection of Ocular Surface

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3245
Author(s):  
Sung-Chul Hong ◽  
Jung-Heun Ha ◽  
Jennifer K. Lee ◽  
Sang Hoon Jung ◽  
Jin-Chul Kim
Keyword(s):  
Animal Model ◽  
Er Stress ◽  
Dry Eye ◽  
Lacrimal Gland ◽  
Ocular Surface ◽  
Inflammatory Responses ◽  
Dry Eye Syndrome ◽  
Inhibitory Effects ◽  
Food Material

Dry eye syndrome (DES) is a corneal disease often characterized by an irritating, itching feeling in the eyes and light sensitivity. Inflammation and endoplasmic reticulum (ER) stress may play a crucial role in the pathogenesis of DES, although the underlying mechanism remains elusive. Aster koraiensis has been used traditionally as an edible herb in Korea. It has been reported to have wound-healing and inhibitory effects against insulin resistance and inflammation. Here, we examined the inhibitory effects of inflammation and ER stress by A. koraiensis extract (AKE) in animal model and human retinal pigmented epithelial (ARPE-19) cells. Oral administration of AKE mitigated DE symptoms, including reduced corneal epithelial thickness, increased the gap between lacrimal gland tissues in experimental animals and decreased tear production. It also inhibited inflammatory responses in the corneal epithelium and lacrimal gland. Consequently, the activation of NF-κB was attenuated by the suppression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Moreover, AKE treatment ameliorated TNF-α-inducible ocular inflammation and thapsigargin (Tg)-inducible ER stress in animal model and human retinal pigmented epithelial (ARPE-19) cells. These results prove that AKE prevents detrimental functional and histological remodeling on the ocular surface and in the lacrimal gland through inhibition of inflammation and ER stress, suggesting its potential as functional food material for improvement of DES.

scholarly journals Comparison of the effects of e-cigarette vapor with cigarette smoke on lung function and inflammation in mice

2018 ◽  
Vol 315 (5) ◽  
pp. L662-L672 ◽  
Author(s):  
Constantinos Glynos ◽  
Sofia-Iris Bibli ◽  
Paraskevi Katsaounou ◽  
Athanasia Pavlidou ◽  
Christina Magkou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cigarette Smoke ◽  
Inflammatory Responses ◽  
Electronic Cigarettes ◽  
Ambient Air ◽  
Lavage Fluid ◽  
Pulmonary Mechanics ◽  
Tissue Elasticity ◽  
Stress Markers

Electronic cigarettes (e-cigs) are advertised as a less harmful nicotine delivery system or as a new smoking cessation tool. We aimed to assess the in vivo effects of e-cig vapor in the lung and to compare them to those of cigarette smoke (CS). We exposed C57BL/6 mice for either 3 days or 4 wk to ambient air, CS, or e-cig vapor containing 1) propylene glycol/vegetable glycerol (PG:VG-Sol; 1:1), 2) PG:VG with nicotine (G:VG-N), or 3) PG:VG with nicotine and flavor (PG:VG-N+F) and determined oxidative stress, inflammation, and pulmonary mechanics. E-cig vapors, especially PG:VG-N+F, increased bronchoalveolar lavage fluid (BALF) cellularity, Muc5ac production, as well as BALF and lung oxidative stress markers at least comparably and in many cases more than CS. BALF protein content at both time points studied was only elevated in the PG:VG-N+F group. After 3 days, PG:VG-Sol altered tissue elasticity, static compliance, and airway resistance, whereas after 4 wk CS was the only treatment adversely affecting these parameters. Airway hyperresponsiveness in response to methacholine was increased similarly in the CS and PG:VG-N+F groups. Our findings suggest that exposure to e-cig vapor can trigger inflammatory responses and adversely affect respiratory system mechanics. In many cases, the added flavor in e-cigs exacerbated the detrimental effects of e-cig vapor. We conclude that both e-cig vaping and conventional cigarette smoking negatively impact lung biology.

scholarly journals PKR-dependent CHOP induction limits hyperoxia-induced lung injury

2011 ◽  
Vol 300 (3) ◽  
pp. L422-L429 ◽  
Author(s):  
Tricia I. Lozon ◽  
Alison J. Eastman ◽  
Gustavo Matute-Bello ◽  
Peter Chen ◽  
Teal S. Hallstrand ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lung Injury ◽  
Er Stress ◽  
Initiation Factor ◽  
Mouse Lung ◽  
Epithelial Cell Line ◽  
Lung Edema ◽  
Α Subunit ◽  
Chop Expression

Supplemental O2is commonly employed in patients with respiratory failure; however, hyperoxia is also a potential contributor to lung injury. In animal models, hyperoxia causes oxidative stress in the lungs, resulting in increased inflammation, edema, and permeability. We hypothesized that oxidative stress from prolonged hyperoxia leads to endoplasmic reticulum (ER) stress, resulting in activation of the unfolded protein response (UPR) and induction of CCAAT enhancer-binding protein homologous protein (CHOP), a transcription factor associated with cell death in the setting of persistent ER stress. To test this hypothesis, we exposed the mouse lung epithelial cell line MLE-12 to 95% O2for 8–24 h and evaluated for evidence of UPR induction and CHOP induction. Hyperoxia caused increased CHOP expression without other evidence of UPR activation. Because CHOP expression is preceded by phosphorylation of the α-subunit of the eukaryotic initiation factor-2 (eIF2α), we evaluated the role of double-stranded RNA-activated protein kinase (PKR), a non-UPR-associated eIF2α kinase. Hyperoxia caused PKR phosphorylation, and RNA interference knockdown of PKR attenuated hyperoxia-induced CHOP expression. In vivo, hyperoxia induced PKR phosphorylation and CHOP expression in the lungs without other biochemical evidence for ER stress. Additionally, Ddit3−/−(CHOP-null) mice had increased lung edema and permeability, indicating a previously unknown protective role for CHOP after prolonged hyperoxia. We conclude that hyperoxia increases CHOP expression via an ER stress-independent, PKR-dependent pathway and that increased CHOP expression protects against hyperoxia-induced lung injury.

α-Lipoic acid protects HAECs from high glucose-induced apoptosis via decreased oxidative stress, ER stress and mitochondrial injury

RSC Advances ◽  
2015 ◽  
Vol 5 (87) ◽  
pp. 70726-70736
Author(s):  
Wenshuang Li ◽  
Changyuan Wang ◽  
Jinyong Peng ◽  
Jing Liang ◽  
Yue Jin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Er Stress ◽  
Lipoic Acid ◽  
High Glucose ◽  
Vascular Diseases ◽  
Mitochondrial Injury ◽  
Wide Range ◽  
Induced Apoptosis

α-Lipoic acid (LA) has a wide range of benefits in treating diabetes mellitus (DM) and DM vascular diseases, however, the specific mechanisms are not clearly understood.

scholarly journals MicroRNA-141-3p Attenuates Oxidative Stress-induced Hepatic Ischemia Reperfusion Injury via Keap1/Nrf2 Pathway

2021 ◽  
Author(s):  
Tingting Li ◽  
Qingsong Chen ◽  
Jiangwen Dai ◽  
Zuotian Huang ◽  
Yunhai Luo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Transplantation ◽  
Reperfusion Injury ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Hepatic Ischemia ◽  
Hepatic Ischemia Reperfusion

Abstract Hepatic ischemia reperfusion injury (IRI) is a major factor affecting the prognosis of liver transplantation through a series of severe cell death and inflammatory responses. MicroRNA-141-3p (miR-141-3p) has been reported to be associated with hepatic steatosis and other liver diseases. However, the potential role of miR-141-3p in hepatic IRI is currently unknown. In the present study, we found that miR-141-3p levels were negatively correlated with alanine aminotransferase (ALT)/aspartate aminotransferase (AST) in liver transplantation patients. The results demonstrated that miR-141-3p was decreased in mouse liver tissue after hepatic IRI in mice and in hepatocytes after hypoxia/reoxygenation (H/R). Overexpression of miR-141-3p directly decreased Kelch-like ECH-associated protein 1 (Keap1) levels and attenuated cell apoptosis in vivo and in vitro, while inhibition of miR-141-3p facilitated apoptosis. Further experiments revealed that overexpression of miR-141-3p also attenuated oxidative stress-induced damage in hepatocytes under H/R conditions. Taken together, our results indicate that miR-141-3p plays a major role in hepatic IRI through the Keap1 signaling pathway, and the present study suggests that miR-141-3p might have a protective effect on hepatic IRI to some extent.

scholarly journals ZBTB20 Positively Regulates Oxidative Stress, Mitochondrial Fission, and Inflammatory Responses of ox-LDL-Induced Macrophages in Atherosclerosis

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Jun Tao ◽  
Junxiong Qiu ◽  
Liuyi Lu ◽  
Lisui Zhang ◽  
Yuan Fu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Level ◽  
Inflammatory Responses ◽  
Oxidized Ldl ◽  
Mitochondrial Fission ◽  
Atherosclerotic Lesion ◽  
Density Lipoprotein ◽  
In Vivo Studies ◽  
Oxidative Stress Level

Atherosclerosis (AS) is one of the most serious and common cardiovascular diseases affecting human health. AS is featured by the accumulation of plaques in vessel walls. The pathophysiology of AS is relevant in the low-density lipoprotein (LDL) uptake by macrophages, as well as the conversion of macrophages to foam cells. However, the mechanisms about how macrophages regulate AS have not been fully elucidated. In this study, we aimed to illuminate the roles of ZBTB20 and to excavate the underlying regulative mechanisms of ZBTB20 in AS. The microarray analysis revealed that ZBTB20 was a hub gene in the oxidative stress and inflammatory responses induced by oxidized LDL (ox-LDL) in AS. Correspondingly, our validation studies showed that ZBTB20 increased in either the human atherosclerotic lesion or the ox-LDL-stimulated macrophages. Moreover, the knockdown of ZBTB20 decreased M1 polarization, suppressed the proinflammatory factors, inhibited mitochondrial fission, and reduced the oxidative stress level of macrophages induced by ox-LDL. The mechanistic studies revealed that the ZBTB20 knockdown suppressed NF-κB/MAPK activation and attenuated the mitochondrial fission possibly via regulating the nucleus translocation of NRF2, a pivotal transcription factor on redox homeostasis. Our in vivo studies showed that the sh-ZBTB20 adenovirus injection could reduce the progression of AS in apolipoprotein E-deficient (ApoE-/-) mice. All in all, these results suggested that ZBTB20 positively regulated the oxidative stress level, mitochondrial fission, and inflammatory responses of macrophages induced by ox-LDL, and the knockdown of ZBTB20 could attenuate the development of AS in ApoE-/- mice.

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