1, 8-cineole protects against ISO-induced heart failure by inhibiting oxidative stress and ER stress in vitro and in vivo

2021 ◽  
Vol 910 ◽  
pp. 174472
Author(s):  
Yu Wang ◽  
Xuan Zhang ◽  
Yao Fu ◽  
Danni Fu ◽  
Dong Zhen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Er Stress

scholarly journals Cytochrome c oxidase III as a mechanism for apoptosis in heart failure following myocardial infarction

2009 ◽  
Vol 297 (4) ◽  
pp. C928-C934 ◽  
Author(s):  
Changgong Wu ◽  
Lin Yan ◽  
Christophe Depre ◽  
Sunil K. Dhar ◽  
You-Tang Shen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Cytochrome C ◽  
Protein Expression ◽  
Cell Viability ◽  
Cytochrome C Oxidase ◽  
Mitochondrial Gene

Cytochrome c oxidase (COX) is composed of 13 subunits, of which COX I, II, and III are encoded by a mitochondrial gene. COX I and II function as the main catalytic components, but the function of COX III is unclear. Because myocardial ischemia affects mitochondrial oxidative metabolism, we hypothesized that COX activity and expression would be affected during postischemic cardiomyopathy. This hypothesis was tested in a monkey model following myocardial infarction (MI) and subsequent pacing-induced heart failure (HF). In this model, COX I protein expression was decreased threefold after MI and fourfold after HF ( P < 0.05 vs. sham), whereas COX II expression remained unchanged. COX III protein expression increased 5-fold after MI and further increased 10-fold after HF compared with sham ( P < 0.05 vs. sham). The physiological impact of COX III regulation was examined in vitro. Overexpression of COX III in mitochondria of HL-1 cells resulted in an 80% decrease in COX I, 60% decrease in global COX activity, 60% decrease in cell viability, and threefold increase in apoptosis ( P < 0.05). Oxidative stress induced by H2O2 significantly ( P < 0.05) increased COX III expression. H2O2 decreased cell viability by 47 ± 3% upon overexpression of COX III, but only by 12 ± 5% in control conditions ( P < 0.05). We conclude that ischemic stress in vivo and oxidative stress in vitro lead to upregulation of COX III, followed by downregulation of COX I expression, impaired COX oxidative activity, and increased apoptosis. Therefore, upregulation of COX III may contribute to the increased susceptibility to apoptosis following MI and subsequent HF.

The Association of Neuronal Stress with Activating Transcription Factor 3 in Dorsal Root Ganglion of in vivo and in vitro Models of Bortezomib- Induced Neuropathy

2018 ◽  
Vol 19 (1) ◽  
pp. 50-64 ◽  
Author(s):  
Yiting Yin ◽  
Xin Qi ◽  
Yuan Qiao ◽  
Huaxiang Liu ◽  
Zihan Yan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Er Stress ◽  
Mitochondrial Dysfunction ◽  
Cell Apoptosis ◽  
Activating Transcription Factor 3 ◽  
Drg Neurons ◽  
Activating Transcription Factor ◽  
Intracellular Oxidative Stress

Background: The notion that proteasome inhibitor bortezomib (BTZ) induced intracellular oxidative stress resulting in peripheral neuropathy has been generally accepted. The association of mitochondrial dysfunction, cell apoptosis, and endoplasmic reticulum (ER) stress with intracellular oxidative stress is ambiguous and still needs to be investigated. The activation of activating transcription factor 3 (ATF3) is a stress-hub gene which was upregulated in dorsal root ganglion (DRG) neurons after different kinds of peripheral nerve injuries. Objective: To investigate a mechanism underlying the action of BTZ-induced intracellular oxidative stress, mitochondrial dysfunction, cell apoptosis, and ER stress via activation of ATF3. </P><P> Methods: Primary cultured DRG neurons with BTZ induced neurotoxicity and DRG from BTZ induced painful peripheral neuropathic rats were used to approach these questions. Results: BTZ administration caused the upregulation of ATF3 paralleled with intracellular oxidative stress, mitochondrial dysfunction, cell apoptosis, and ER stress in DRG neurons both in vitro and in vivo. Blocking ATF3 signaling by small interfering RNA (siRNA) gene silencing technology resulted in decreased intracellular oxidative stress, mitochondrial dysfunction, cell apoptosis, and ER stress in DRG neurons after BTZ treatment. This study exhibited important mechanistic insight into how BTZ induces neurotoxicity through the activation of ATF3 resulting in intracellular oxidative stress, mitochondrial dysfunction, cell apoptosis, and ER stress and provided a novel potential therapeutic target by blocking ATF3 signaling.

scholarly journals Naringenin Attenuates Myocardial Ischemia-Reperfusion Injury via cGMP-PKGIα Signaling and In Vivo and In Vitro Studies

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Li-Ming Yu ◽  
Xue Dong ◽  
Jian Zhang ◽  
Zhi Li ◽  
Xiao-Dong Xue ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Er Stress ◽  
Ischemia Reperfusion Injury ◽  
Heart Function ◽  
Ischemia Reperfusion ◽  
Guanosine Monophosphate ◽  
Myocardial Ischemia Reperfusion

Endoplasmic reticulum (ER) stress and oxidative stress contribute greatly to myocardial ischemia-reperfusion (MI/R) injury. Naringenin, a flavonoid derived from the citrus genus, exerts cardioprotective effects. However, the effects of naringenin on ER stress as well as oxidative stress under MI/R condition and the detailed mechanisms remain poorly defined. This study investigated the protective effect of naringenin on MI/R-injured heart with a focus on cyclic guanosine monophosphate- (cGMP-) dependent protein kinase (PKG) signaling. Sprague-Dawley rats were treated with naringenin (50 mg/kg/d) and subjected to MI/R surgery with or without KT5823 (2 mg/kg, a selective inhibitor of PKG) cotreatment. Cellular experiment was conducted on H9c2 cardiomyoblasts subjected to simulated ischemia-reperfusion treatment. Before the treatment, the cells were incubated with naringenin (80 μmol/L). PKGIα siRNA was employed to inhibit PKG signaling. Our in vivo and in vitro data showed that naringenin effectively improved heart function while it attenuated myocardial apoptosis and infarction. Furthermore, pretreatment with naringenin suppressed MI/R-induced oxidative stress as well as ER stress as evidenced by decreased superoxide generation, myocardial MDA level, gp91phox expression, and phosphorylation of PERK, IRE1α, and EIF2α as well as reduced ATF6 and CHOP. Importantly, naringenin significantly activated myocardial cGMP-PKGIα signaling while inhibition of PKG signaling with KT5823 (in vivo) or siRNA (in vitro) not only abolished these actions but also blunted naringenin’s inhibitory effects against oxidative stress and ER stress. In summary, our study demonstrates that naringenin treatment protects against MI/R injury by reducing oxidative stress and ER stress via cGMP-PKGIα signaling. Its cardioprotective effect deserves further clinical study.

scholarly journals Papel del estrés oxidativo y nitrosativo en la hipertrofia cardiaca y remodelación ventricular

2019 ◽  
Vol 35 (2) ◽  
pp. 82-95
Author(s):  
Alejandro Giraldo
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Nitrosative Stress ◽  
Ventricular Remodeling ◽  
Estrés Oxidativo ◽  
Palabras Clave

Objetivo: hacer una revisión de los mecanismos moleculares del estrés oxidativo y nitrosativo en la fisiopatología de la falla cardiaca. Metodología: se hizo una búsqueda en Medline (Pubmed) con las palabras clave: oxidative stress, ventricular remodeling, heart failure y nitrosative stress. Se consultó además bibliografía citada por autores de reconocida trayectoria en investigación en este tema. Resultados: se seleccionaron los 112 artículos más relevantes en el tema de estrés oxidativo/ nitrosativo que se relacionarán con falla cardiaca. Conclusiones: las respuestas de estrés de los cardiomiocitos y del tejido miocárdico es muy probable que constituyan un aspecto significativo del desarrollo de patologías cardiacas que desencadenan como evento final su progresión hacia falla cardiaca. El estrés oxidativo es un tema común en la fisiopatología de la cardiomiopatía isquémica y no isquémica. Patologías cardiacas como la falla cardiaca son usualmente precedidas de hipertrofia cardiaca secundaria, al menos en parte, a la generación de especies reactivas del oxígeno en los cardiomiocitos. Varios son los mecanismos implicados en la remodelación ventricular y progresión de la falla cardiaca que dependen de alteraciones homeostáticas en los sistemas que generan estrés oxidativo y/o nitrosativo. La discusión se centra en la reciente evidencia derivada de investigaciones llevadas a cabo tanto in vitro en cardiomiocitos cultivados como in vivo en modelos experimentales de patologías cardiacas. Las implicaciones clínicas de los recientes descubrimientos aunque son muy prometedoras para la terapéutica de la falla cardiaca, aun no han logrado trasladarse con total éxito a la práctica clínica en los ensayos clínicos realizados hasta el momento

scholarly journals Hispidulin Attenuates Cardiac Hypertrophy by Improving Mitochondrial Dysfunction

2020 ◽  
Vol 7 ◽  
Author(s):  
Yan Wang ◽  
Zengshuo Xie ◽  
Nan Jiang ◽  
Zexuan Wu ◽  
Ruicong Xue ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Mitochondrial Function ◽  
Specific Inhibitor ◽  
Cardiomyocyte Hypertrophy ◽  
Mitochondrial Morphology ◽  
Protective Effects

Cardiac hypertrophy is a pathophysiological response to harmful stimuli. The continued presence of cardiac hypertrophy will ultimately develop into heart failure. The mitochondrion is the primary organelle of energy production, and its dysfunction plays a crucial role in the progressive development of heart failure from cardiac hypertrophy. Hispidulin, a natural flavonoid, has been substantiated to improve energy metabolism and inhibit oxidative stress. However, how hispidulin regulates cardiac hypertrophy and its underlying mechanism remains unknown. We found that hispidulin significantly inhibited pressure overload-induced cardiac hypertrophy and improved cardiac function in vivo and blocked phenylephrine (PE)-induced cardiomyocyte hypertrophy in vitro. We further proved that hispidulin remarkably improved mitochondrial function, manifested by increased electron transport chain (ETC) subunits expression, elevated ATP production, increased oxygen consumption rates (OCR), normalized mitochondrial morphology, and reduced oxidative stress. Furthermore, we discovered that Sirt1, a well-recognized regulator of mitochondrial function, might be a target of hispidulin, as evidenced by its upregulation after hispidulin treatment. Cotreatment with EX527 (a Sirt1-specific inhibitor) and hispidulin nearly completely abolished the antihypertrophic and protective effects of hispidulin on mitochondrial function, providing further evidence that Sirt1 could be the pivotal downstream effector of hispidulin in regulating cardiac hypertrophy.

scholarly journals Echinacoside Upregulates Sirt1 to Suppress Endoplasmic Reticulum Stress and Inhibit Extracellular Matrix Degradation In Vitro and Ameliorates Osteoarthritis In Vivo

2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Zhen Lin ◽  
Cheng Teng ◽  
Libin Ni ◽  
Zhao Zhang ◽  
Xinlei Lu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Underlying Mechanism ◽  
Cellular Damage ◽  
Cellular Effects ◽  
Tert Butyl Hydroperoxide ◽  
Ecm Degradation

Background. Osteoarthritis (OA) is a progressive illness that destroys cartilage. Oxidative stress is a major contributor of OA, while endoplasmic reticulum (ER) stress is the key cellular damage under oxidative stress in chondrocytes. Echinacoside (ECH) is the main extract and active substance of Cistanche, with potent antioxidative stress (OS) properties, and currently under clinical trials in China. However, its function in OA is yet to be determined. Purpose. We aimed to explore the specific role of ECH in the occurrence and development of OA and its underlying mechanism in vivo and in vitro. Methods. After the mice were anesthetized, the bilateral medial knee joint meniscus resection was performed to establish the DMM model. TBHP was used to induce oxidative stress to establish the OA model in chondrocytes in vitro. Western blot and RT-PCR were used to evaluate the level of ER stress-related biomarkers such as p-PERK/PERK, GRP78, ATF4, p-eIF2α/eIF2α, and CHOP and apoptosis-related proteins such as BAX, Bcl-2, and cleaved caspase-3. Meanwhile, we used SO staining, immunofluorescence, and immunohistochemical staining to evaluate the pharmacological effects of ECH in mice in vivo. Results. We demonstrated the effectiveness of ECH in suppressing ER stress and restoring ECM metabolism in vitro. In particular, ECH was shown to suppress tert-Butyl hydroperoxide- (TBHP-) induced OS and subsequently lower the levels of p-PERK/PERK, GRP78, ATF4, p-eIF2α/eIF2α, and CHOP in vitro. Simultaneously, ECH reduced MMP13 and ADAMTS5 levels and promoted Aggrecan and Collagen II levels, suggesting ECM degradation suppression. Moreover, we showed that ECH mediates its cellular effects via upregulation of Sirt1. Lastly, we confirmed that ECH can protect against OA in mouse OA models. Conclusion. In summary, our findings indicate that ECH can inhibit ER stress and ECM degradation by upregulating Sirt1 in mouse chondrocytes treated with TBHP. It can also prevent OA development in vivo.

scholarly journals Metformin and Probiotics Interplay in Amelioration of Ethanol-Induced Oxidative Stress and Inflammatory Response in an In Vitro and In Vivo Model of Hepatic Injury

2021 ◽  
Vol 2021 ◽  
pp. 1-31
Author(s):  
Farhin Patel ◽  
Kirti Parwani ◽  
Dhara Patel ◽  
Palash Mandal
Keyword(s):  
Oxidative Stress ◽  
Lipid Metabolism ◽  
Liver Injury ◽  
Inflammatory Response ◽  
Er Stress ◽  
Hepg2 Cells ◽  
Hepatic Injury ◽  
And Oxidative Stress

Alcohol-induced liver injury implicates inflammation and oxidative stress as important mediators. Despite rigorous research, there is still no Food and Drug Administration (FDA) approved therapies for any stage of alcoholic liver disease (ALD). Interestingly, metformin (Met) and several probiotic strains possess the potential of inhibiting alcoholic liver injury. Therefore, we investigated the effectiveness of combination therapy using a mixture of eight strains of lactic acid-producing bacteria, commercialized as Visbiome® (V) and Met in preventing the ethanol-induced hepatic injury using in vitro and in vivo models. Human HepG2 cells and male Wistar rats were exposed to ethanol and simultaneously treated with probiotic V or Met alone as well as in combination. Endoplasmic reticulum (ER) stress markers, inflammatory markers, lipid metabolism, reactive oxygen species (ROS) production, and oxidative stress were evaluated, using qRT-PCR, Oil red O staining, fluorimetry, and HPLC. In vitro, probiotic V and Met in combination prevented ethanol-induced cellular injury, ER stress, oxidative stress, and regulated lipid metabolism as well as inflammatory response in HepG2 cells. Probiotic V and Met also promoted macrophage polarization towards the M2 phenotype in ethanol-exposed RAW 264.7 macrophage cells. In vivo, combined administration of probiotic V and Met ameliorated the histopathological changes, inflammatory response, hepatic markers (liver enzymes), and lipid metabolism induced by ethanol. It also improved the antioxidant markers (HO-1 and Nrf-2), as seen by their protein levels in both HepG2 cells as well as liver tissue using ELISA. Hence, probiotic V may act, in addition to the Met, as an effective preventive treatment against ethanol-induced hepatic injury.

scholarly journals Selenoprotein V Protects Against Oxidative Stress, Endoplasmic Reticulum Stress, and Apoptosis

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1858-1858
Author(s):  
Xu Zhang ◽  
Wei Xiong ◽  
Jiaqiang Huang ◽  
Xin Gen Lei
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Caspase 9 ◽  
Funding Sources ◽  
Control Plasmid ◽  
Selenoprotein V ◽  
Related Proteins

Abstract Objectives Selenoprotein V (SELENOV) contains a thioredoxin-like fold and a conserved CxxU motif with a potential redox function. Three experiments were performed to assess its in vivo and in vitro roles and mechanisms in coping with different oxidant insults. Methods In Expt.1, SELENOV knockout (KO) and wildtype (WT) mice (male, 8-wk old) were given an IP injection of saline, diquat (DQ, 12.5 mg/kg), or acetaminophen (APAP, 300 mg/kg) (n = 10), and killed 5 h after the injection to collect liver and blood. In Expt. 2, primary hepatocytes were isolated from the 2 genotypes, cultured in complete Williams's medium E, and treated with DQ (0, 0.25 and 0.75 mM) and APAP (0, 1, 3, and 6 mM) for 12 h. In Expt. 3, 293 T cells were transfected with a control plasmid (GFP) or the plasmid containing Selenov gene (full length, OE) and treated with APAP (0, 1, 2, and 4 mM) for 24 h or H2O2 (0.1, 0.2, and 0.4 mM) for 12 h. Results In Expt. 1, the DQ and APAP injections caused greater (P &lt; 0.05) rises in serum alanine aminotransferase activities, hepatic malondialdehyde (MDA) and carbonyl contents, endoplasmic reticulum (ER) stress-related proteins (BIP and CHOP), apoptosis-related proteins (FAK and caspase 9), and 3-nitrotyrosine, along with lower total anti-oxidizing-capability (T-AOC) and severer hepatocyte necrosis in the central lobular areas, in the KO than in the WT. In Expt. 2, the DQ and APAP treatments induced elevated (P &lt; 0.05) cell death (20–40%), MDA contents (25–35%), and decreased (P &lt; 0.05) T-AOC (50–65%) in the KO hepatocytes than in the WT cells. The KO hepatocytes treated with APAP displayed a sharp decline (P &lt; 0.05) in cellular total respiration ability than the WT cells. In Expt. 3, the OE cells had greater viability and T-AOC and lower reactive oxygen species, MDA, and carbonyl contents after the APAP and H2O2 exposures (all at P &lt; 0.05) than the controls. Moreover, the OE cells had greater (P &lt; 0.05) redox enzyme activities (GPX, TrxR, and SOD), and lower (P &lt; 0.05) expressions of ER stress-related genes (Atf4, Atf6, Bip, Xpp1t, Xbp1s, and Chop) and proteins (BIP, CHOP, FAK, caspase 9) than the controls after the treatment of H2O2 (0.4 mM). Conclusions Our data revealed the in vivo and in vitro roles and mechanisms of SELENOV in protecting against oxidative stress, ER stress, and apoptosis induced by pro-oxidants. Funding Sources This research is supported in part by an NSFC grant #31,320,103,920.

scholarly journals SUN-189 FOLLISTATIN PROTECTS AGAINST ER STRESS-INDUCED OXIDATIVE STRESS AND APOPTOSIS BOTH IN VITRO AND IN VIVO IN CKD

2019 ◽  
Vol 4 (7) ◽  
pp. S237
Author(s):  
N. Mehta ◽  
A. Gava ◽  
D. Zhang ◽  
B. Gao ◽  
J. KREPINSKY
Keyword(s):  
Oxidative Stress ◽  
Er Stress

scholarly journals LCZ696 Ameliorates Oxidative Stress and Pressure Overload-Induced Pathological Cardiac Remodeling by Regulating the Sirt3/MnSOD Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Shi Peng ◽  
Xiao-feng Lu ◽  
Yi-ding Qi ◽  
Jing Li ◽  
Juan Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Pressure Overload ◽  
Neonatal Rat ◽  
Cardiomyocyte Hypertrophy ◽  
Rat Cardiomyocytes ◽  
Pathological Cardiac Hypertrophy

Aims. We aimed to investigate whether LCZ696 protects against pathological cardiac hypertrophy by regulating the Sirt3/MnSOD pathway. Methods. In vivo, we established a transverse aortic constriction animal model to establish pressure overload-induced heart failure. Subsequently, the mice were given LCZ696 by oral gavage for 4 weeks. After that, the mice underwent transthoracic echocardiography before they were sacrificed. In vitro, we introduced phenylephrine to prime neonatal rat cardiomyocytes and small-interfering RNA to knock down Sirt3 expression. Results. Pathological hypertrophic stimuli caused cardiac hypertrophy and fibrosis and reduced the expression levels of Sirt3 and MnSOD. LCZ696 alleviated the accumulation of oxidative reactive oxygen species (ROS) and cardiomyocyte apoptosis. Furthermore, Sirt3 deficiency abolished the protective effect of LCZ696 on cardiomyocyte hypertrophy, indicating that LCZ696 induced the upregulation of MnSOD and phosphorylation of AMPK through a Sirt3-dependent pathway. Conclusions. LCZ696 may mitigate myocardium oxidative stress and apoptosis in pressure overload-induced heart failure by regulating the Sirt3/MnSOD pathway.

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