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.

scholarly journals Low-density lipoprotein oxidation, antioxidants, and atherosclerosis: a clinical biochemistry perspective

1996 ◽  
Vol 42 (4) ◽  
pp. 498-506 ◽  
Author(s):  
I Jialal ◽  
S Devaraj
Keyword(s):  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Atherosclerotic Lesion ◽  
Density Lipoprotein ◽  
Direct Methods ◽  
Ldl Oxidation ◽  
Low Density ◽  
Indirect Measures ◽  
Oxidatively Modified

Abstract Cardiovascular disease is the leading cause of mortality in westernized populations. An increased concentration of plasma low-density lipoprotein (LDL) cholesterol constitutes a major risk factor for atherosclerosis. Several lines of evidence support a role for oxidatively modified LDL in atherosclerosis and for its in vivo existence. Antioxidants have been shown to decrease atherosclerotic lesion formation in animal models and decrease LDL oxidation; the evaluation of LDL oxidation in vivo is therefore very important. However, there is a paucity of methods for direct measurement of LDL oxidation. Of the direct methods currently available, the preferred ones seem to be the measurement of F2-isoprostanes, autoantibodies to epitopes on oxidized LDL, and the assessment of antioxidant status. Of the indirect measures, the most uniformly accepted procedure is examining the oxidative susceptibility of isolated LDL by monitoring conjugated diene formation.

scholarly journals Quantification of malondialdehyde and 4-hydroxynonenal adducts to lysine residues in native and oxidized human low-density lipoprotein

1997 ◽  
Vol 322 (1) ◽  
pp. 317-325 ◽  
Author(s):  
Jesús R. REQUENA ◽  
Min Xin FU ◽  
Mahtab U. AHMED ◽  
Alicia J. JENKINS ◽  
Timothy J. LYONS ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gas Chromatography ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Thiobarbituric Acid ◽  
Low Density ◽  
Lysine Residues

Malondialdehyde (MDA) and 4-hydroxynonenal (HNE) are major end-products of oxidation of polyunsaturated fatty acids, and are frequently measured as indicators of lipid peroxidation and oxidative stress in vivo. MDA forms Schiff-base adducts with lysine residues and cross-links proteins in vitro; HNE also reacts with lysines, primarily via a Michael addition reaction. We have developed methods using NaBH4 reduction to stabilize these adducts to conditions used for acid hydrolysis of protein, and have prepared reduced forms of lysine-MDA [3-(Nε-lysino)propan-1-ol (LM)], the lysine-MDA-lysine iminopropene cross-link [1,3-di(Nε-lysino)propane (LML)] and lysine-HNE [3-(Nε-lysino)-4-hydroxynonan-1-ol (LHNE)]. Gas chromatography/MS assays have been developed for quantification of the reduced compounds in protein. RNase incubated with MDA or HNE was used as a model for quantification of the adducts by gas chromatography/MS. There was excellent agreement between measurement of MDA bound to RNase as LM and LML, and as thiobarbituric acid-MDA adducts measured by HPLC; these adducts accounted for 70Ő80% of total lysine loss during the reaction with MDA. LM and LML (0.002Ő0.12mmol/mol of lysine) were also found in freshly isolated low-density lipoprotein (LDL) from healthy subjects. LHNE was measured in RNase treated with HNE, but was not detectable in native LDL. LM, LML and LHNE increased in concert with the formation of conjugated dienes during the copper-catalysed oxidation of LDL, but accounted for modification of < 1% of lysine residues in oxidized LDL. These results are the first report of direct chemical measurement of MDA and HNE adducts to lysine residues in LDL. LM, LML and LHNE should be useful as biomarkers of lipid peroxidative modification of protein and of oxidative stress in vitro and in vivo.

scholarly journals N-acetyl cysteine induces quiescent-like pancreatic stellate cells from an active state and attenuates cancer-stroma interactions

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Haimin Feng ◽  
Taiki Moriyama ◽  
Kenoki Ohuchida ◽  
Nan Sheng ◽  
Chika Iwamoto ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pancreatic Cancer ◽  
Stress Level ◽  
Lipid Droplets ◽  
Stellate Cells ◽  
Pancreatic Stellate Cells ◽  
Oxidative Stress Level ◽  
Acetyl Cysteine ◽  
And Migration

Abstract Background Pancreatic stellate cells (PSCs) occupy the majority of the pancreatic cancer microenvironment, contributing to aggressive behavior of pancreatic cancer cells (PCCs). Recently, anti-fibrotic agents have proven to be an effective strategy against cancer, but clinical trials have shown little efficacy, and the driving mechanism remains unknown. N-acetyl-cysteine (NAC) is often used for pulmonary cystic fibrosis. Pioglitazone, an agonist of peroxisome proliferator-activated receptor gamma, was habitually used for type II diabetes, but recently reported to inhibit metastasis of PCCs. However, few studies have focused on the effects of these two agents on cancer-stromal interactions. Method We evaluated the expression of α-smooth muscle actin (α-SMA) and the number of lipid droplets in PSCs cultured with or without NAC. We also evaluated changes in invasiveness, viability, and oxidative level in PSCs and PCCs after NAC treatment. Using an indirect co-culture system, we investigated changes in viability, invasiveness, and migration of PSCs and PCCs. Combined treatment effects of NAC and Pioglitazone were evaluated in PSCs and PCCs. In vivo, we co-transplanted KPC-derived organoids and PSCs to evaluate the effects of NAC and Pioglitazone’s combination therapy on subcutaneous tumor formation and splenic xenografted mouse models. Results In vitro, NAC inhibited the viability, invasiveness, and migration of PSCs at a low concentration, but not those of PCCs. NAC treatment significantly reduced oxidative stress level and expression of α-SMA, collagen type I in PSCs, which apparently present a quiescent-like state with a high number of lipid droplets. Co-cultured PSCs and PCCs mutually promoted the viability, invasiveness, and migration of each other. However, these promotion effects were attenuated by NAC treatment. Pioglitazone maintained the NAC-induced quiescent-like state of PSCs, which were reactivated by PCC-supernatant, and enhanced chemosensitivity of PCCs. In vivo, NAC and Pioglitazone’s combination suppressed tumor growth and liver metastasis with fewer stromal components and oxidative stress level. Conclusion NAC suppressed activated PSCs and attenuated cancer-stromal interactions. NAC induces quiescent-like PSCs that were maintained in this state by pioglitazone treatment.

scholarly journals Caffeic Acid Prevents Vascular Oxidative Stress and Atherosclerosis against Atherosclerogenic Diet in Rats

2022 ◽  
Vol 2022 ◽  
pp. 1-8
Author(s):  
Ying Wang ◽  
Gurpreet Kaur ◽  
Manish Kumar ◽  
Ajay Singh Kushwah ◽  
Atul Kabra ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Profile ◽  
Caffeic Acid ◽  
Stress Level ◽  
Therapeutic Potential ◽  
Atherosclerotic Lesion ◽  
Chow Diet ◽  
Oxidative Stress Level ◽  
Normal Chow ◽  
Normal Chow Diet

Diet and lifestyle play a crucial role in the progress of some cardiovascular disorders (CVDs). Rising interest in natural products and their pharmacological investigations witnessed therapeutic potential against CVDs. Caffeic acid (CA) is an organic composite hydroxycinnamic acid derivative classified among phenolics. It is a secondary metabolite biosynthesized in all plant species in the form of ester conjugates. The reported pharmacological activities of CA are neuroprotective, cardioprotective, hypoglycemic, antioxidant, and immunomodulatory properties. This work is aimed to examine the outcome of CA in atherogenic diet- (Ath-) induced rat model on lipid profile changes and endothelium function. The method involves a study duration of 35 days utilizing (n = 6) male Wistar rats (180–200 g) that were fed either normal chow or Ath. Study groups are given (i) normal chow diet, (ii) Ath, (iii) Ath + CA (25 or 50 mg/kg, p.o.), (iv) normal chow diet + CA (50 mg/kg, p.o.), and (v) Ath + Atorvastatin (ATORVA) (5 mg/kg, p.o.). Blood samples were collected at the end of the study to measure serum lipid profile, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and tissue oxidative stress level. Hemodynamic parameters and aorta staining were performed. CA treatment ameliorated lipid profile and significantly reduced the oxidative stress level. Aorta staining examination revealed a marked reduction of the atherosclerotic lesions. These findings suggested that CA is an effective treatment approach for preventing atherosclerotic lesion progression attributed to protection against oxidative stress and various enzymatic activities in the Ath model.

scholarly journals Oxidized LDL Disrupts Metabolism and Inhibits Macrophage Survival by Activating a miR-9/Drp1/Mitochondrial Fission Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Ting Xin ◽  
Chengzhi Lu ◽  
Jing Zhang ◽  
Jiaxin Wen ◽  
Shuangbin Yan ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Cholesterol Metabolism ◽  
Oxidized Ldl ◽  
Mitochondrial Fission ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
The Novel ◽  
Macrophage Viability

Mitochondrial dysfunction is associated with macrophage damage, but the role of mitochondrial fission in macrophage cholesterol metabolism is not fully understood. In this study, we explored the influences of miR-9 and mitochondrial fission on macrophage viability and cholesterol metabolism. Macrophages were incubated with oxidized low-density lipoprotein (ox-LDL) in vitro, after which mitochondrial fission, cell viability, and cholesterol metabolism were examined using qPCR, ELISAs, and immunofluorescence. ox-LDL treatment significantly increased Drp1-associated mitochondrial fission. Transfection of Drp1 siRNA significantly reduced cell death, attenuated oxidative stress, and inhibited inflammatory responses in ox-LDL-treated macrophages. Interestingly, inhibition of Drp1-related mitochondrial fission also improved cholesterol metabolism by balancing the transcription of cholesterol influx/efflux enzymes. We also found that miR-9 was downregulated in ox-LDL-treated macrophages, and administration of a miR-9 mimic decreased Drp1 transcription and mitochondrial fission, as well as its effects. These results indicate that signaling via the novel miR-9/Drp1/mitochondrial fission axis is a key determinant of macrophage viability and cholesterol metabolism.

Regulation of Influenza Virus-Caused Oxidative Stress by Kegan Liyan Oral Prescription, as Monitored by Ascorbyl Radical ESR Signals

2009 ◽  
Vol 37 (06) ◽  
pp. 1167-1177 ◽  
Author(s):  
Shaojin Duan ◽  
Lizhen Gu ◽  
Yanyun Wang ◽  
Rongbo Zheng ◽  
Jingfen Lu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ascorbic Acid ◽  
Influenza Virus ◽  
Stress Level ◽  
Down Regulation ◽  
Oxidative Stress Level ◽  
Virus Pneumonia ◽  
Healthy Control

To study the oxidative stress level of the influenza virus A FM1 subset-infected mouse in intranasal inhalation as a model, we employ an ascorbyl radical's ESR (electron spin resonance) spectrum as an oxidative stress biomarker. These infected mice were pretreated with Ribavirin, ascorbic acid, superoxide dismutase (SOD) or Kegan Liyan oral prescription (KGLY, proprietary Chinese medicine for influenza and common cold) in the stomach tube for 3 days, and then followed by the virus-infecting for 4 days. On the 4th day, samples were collected. It is recognized the strength of ascorbyl radical's ESR signal ( A -.) (a H4 = 0.177 Gauss, g = 2.00517) denotes oxidative stress level in vivo and in vitro. The magnitude of ESR spectrum (28.65 ± 10.71 AU) in mice infected with influenza virus was significantly higher than those of healthy control mice (19.10 ± 3.61 AU). Serum A -. in mice treated with Ribavirin, ascorbic acid, SOD and KGLY declined to 19.70 ± 6.05, 18.50 ± 2.93 and 16.25 ± 3.59, 18.40 ± 2.14 AU respectively. It is close to A -. signal height in healthy controls via down-regulation of the influenza virus-caused oxidative stress level getting decline in the lung index of pneumonia as compare to those of untreated healthy and the influenza virus infected mice pneumonia. It is well known that SOD can prevent the influenza virus pneumonia enhancing mouse survival rate; Ribavirin can treat viral diseases. Data from this study suggested that KGLY may indirectly relieve influenza virus-infected pneumonia via down- regulation of virus caused oxidative stress coupled with a redox reaction cascade as ribavirin, ascorbic acid and SOD.

Development of the Express Method for Determining the Oxidative Stress Level of the Population

Food Industry ◽  
2018 ◽  
Vol 3 (4) ◽  
Author(s):  
Ekaterina V. Pastushkova ◽  
Olga V. Chugunova ◽  
Leonid S. Volkanin
Keyword(s):  
Oxidative Stress ◽  
Stress Level ◽  
Express Method ◽  
Oxidative Stress Level

scholarly journals The Potential Neuroprotective Role of Free and Encapsulated Quercetin Mediated by miRNA against Neurological Diseases

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1318
Author(s):  
Tarek Benameur ◽  
Raffaella Soleti ◽  
Chiara Porro
Keyword(s):  
Inflammatory Responses ◽  
Pathological Condition ◽  
Neurological Diseases ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
In Vivo Studies ◽  
Innovative Drug ◽  
Chronic Neuroinflammation

Chronic neuroinflammation is a pathological condition of numerous central nervous system (CNS) diseases such as Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis and many others. Neuroinflammation is characterized by the microglia activation and concomitant production of pro-inflammatory cytokines leading to an increasing neuronal cell death. The decreased neuroinflammation could be obtained by using natural compounds, including flavonoids known to modulate the inflammatory responses. Among flavonoids, quercetin possess multiple pharmacological applications including anti-inflammatory, antitumoral, antiapoptotic and anti-thrombotic activities, widely demonstrated in both in vitro and in vivo studies. In this review, we describe the recent findings about the neuroprotective action of quercetin by acting with different mechanisms on the microglial cells of CNS. The ability of quercetin to influence microRNA expression represents an interesting skill in the regulation of inflammation, differentiation, proliferation, apoptosis and immune responses. Moreover, in order to enhance quercetin bioavailability and capacity to target the brain, we discuss an innovative drug delivery system. In summary, this review highlighted an important application of quercetin in the modulation of neuroinflammation and prevention of neurological disorders.

scholarly journals Alcohol-and-HIV-Induced Lysosomal Dysfunction Regulates Extracellular Vesicles Secretion in Vitro and in Liver-Humanized Mice

Biology ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 29
Author(s):  
Raghubendra Singh Dagur ◽  
Moses New-Aaron ◽  
Murali Ganesan ◽  
Weimin Wang ◽  
Svetlana Romanova ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Extracellular Vesicles ◽  
Treated Group ◽  
Human Hepatocytes ◽  
In Vivo Studies ◽  
People Living With Hiv ◽  
Humanized Mouse Model ◽  
And Function

Background: Alcohol abuse is common in people living with HIV-1 and dramaticallyenhances the severity of HIV-induced liver damage by inducing oxidative stress and lysosomaldysfunction in the liver cells. We hypothesize that the increased release of extracellular vesicles(EVs) in hepatocytes and liver humanized mouse model is linked to lysosome dysfunction. Methods:The study was performed on primary human hepatocytes and human hepatoma RLWXP-GFP (Huh7.5 cells stably transfected with CYP2E1 and XPack-GFP) cells and validated on ethanol-fed liverhumanizedfumarylacetoacetate hydrolase (Fah)-/-, Rag2-/-, common cytokine receptor gamma chainknockout (FRG-KO) mice. Cells and mice were infected with HIV-1ADA virus. Results: We observedan increase in the secretion of EVs associated with a decrease in lysosomal activity and expressionof lysosomal-associated membrane protein 1. Next-generation RNA sequencing of primary humanhepatocytes revealed 63 differentially expressed genes, with 13 downregulated and 50 upregulatedgenes in the alcohol–HIV-treated group. Upstream regulator analysis of differentially expressedgenes through Ingenuity Pathway Analysis identified transcriptional regulators affecting downstreamgenes associated with increased oxidative stress, lysosomal associated disease, and function andEVs biogenesis. Our in vitro findings were corroborated by in vivo studies on human hepatocytetransplantedhumanized mice, indicating that intensive EVs’ generation by human hepatocytes andtheir secretion to serum was associated with increased oxidative stress and reduction in lysosomalactivities triggered by HIV infection and ethanol diet. Conclusion: HIV-and-ethanol-metabolisminducedEVs release is tightly controlled by lysosome status in hepatocytes and participates in thedevelopment of double-insult-induced liver injury.

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