scholarly journals Shen Qi Li Xin formula improves chronic heart failure through balancing mitochondrial fission and fusion via upregulation of PGC-1α

2021 ◽  
Vol 71 (1) ◽  
Author(s):  
Yan-Bo Sui ◽  
Jian Xiu ◽  
Jin-Xuan Wei ◽  
Pei-Pei Pan ◽  
Bi-Hong Sun ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Chronic Heart Failure ◽  
Cell Viability ◽  
Heart Function ◽  
Mitochondrial Fission ◽  
Tunel Staining ◽  
Action Mechanism ◽  
Related Proteins

Abstract Background Our previous study proved that Shen Qi Li Xin formula (SQLXF) improved the heart function of chronic heart failure (CHF) patients, while the action mechanism remains unclear. Methods H&E staining and TUNEL staining were performed to measure myocardial damages. Western blot was used to examine the expression of proteins. Moreover, CCK-8 assay and flow cytometry were used to measure cell viability and cell apoptosis, respectively. Concentrations of ATP and ROS in cells, and mitochondrial membrane potential (MMP) were detected to estimate oxidative stress. Results In vivo, we found that SQLXF improved cardiac hemodynamic parameters, reduced LDH, CK-MB and BNP production, and attenuated myocardial damages in CHF rats. Besides, SQLXF promoted mitochondrial fusion-related proteins expression and inhibited fission-related proteins expression in CHF rats and oxygen glucose deprivation/reoxygenation (OGD/R)-induced cardiac myocytes (CMs). In vitro, our data show that certain dose of SQLXF inhibited OGD/R-induced CMs apoptosis, cell viability decreasing and oxidative stress. Conclusion Overall, certain dose of SQLXF could effectively improve the cardiac function of CHF rats through inhibition of CMs apoptosis via balancing mitochondrial fission and fusion. Our data proved a novel action mechanism of SQLXF in CHF improvement, and provided a reference for clinical.

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.

scholarly journals Dl-3-n-Butylphthalide Promotes Cardiac Function, Inhibit Oxidative Stress and Myocardial Apoptosis of Chronic Heart Failure Mice via Stimulating Nrf2/HO-1 pathway

2021 ◽  
Author(s):  
Zhongyu Wang ◽  
Yan Zhang ◽  
Chun Yang ◽  
Hongliang Yang
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Signaling Pathway ◽  
Myocardial Injury ◽  
Heart Function ◽  
Regulatory Protein ◽  
Camp Response Element Binding ◽  
Tunel Staining ◽  
Coronary Artery Ligation ◽  
Artery Ligation

Abstract PurposeHeart failure (HF) continues to threat the human health and plagues the world, however, there are limited effective drugs for HF. We aimed to investigate the protective effect of Dl-3-n-Butylphthalide (NBP) on myocardial injury in heart failure mice, and to study regulation mechanisms with Nrf2/HO-1/Ca2+-SERCA2a axis. MethodsSixty C57BL/6J mice were grouped into five groups using a random number table: sham group (Sham), Heart Failure model group (HF), Heart Failure+ NBP group (HN), Heart Failure+NBP+Nrf2 inhibitor (HNM), Heart Failure+ NBP + calmodulin-dependent protein kinase II (CaMKⅡ) antagonist, KN93 (HNK). The HF mice was prepared using left anterior descending coronary artery ligation. As animal model preparation, the heart function was detected using echocardiography. H&E and MASSON trichrome staining were performed to identify myocardial injury; The apoptosis of myocardial was examined by TUNEL staining assay. The levels of different oxidative stress-related proteins were measured through ELISA assay ; The reactive oxygen species and Nrf2 expression in heart tissue were observed with immunofluorescence assay. The levels of SERCA2a, calmodulin, endoplasmic reticulum stress regulatory protein and Nrf2/HO-1 protein were measured using western blotting. ResultsThe results demonstrated that NBP can significantly promote heart function, relieve the injury and inhibit cell apoptosis, meanwhile, reduce ERS injury in heart failure mice through increasing SERCA2a level and reducing Ca2+ influx. Finally, NBP was demonstrated to reduce CaMKⅡphosphorylation levels and decrease cAMP-response element binding protein phosphorylation levels, which suggested that NBP could also activate Nrf2/HO-1 signaling pathway. ConclusionsThis study identified that NPBs treatment promotes the cardiomyocytes ERS and alleviates myocardial injury in heart failure mice which is related with stimulating Nrf2/HO-1 signaling pathway, regulating Ca2+-SERCA2a and reducing Ca2+ influx.

Abstract 58: Dicarbonyl Stress and Diabetic Heart Failure: The Role of Endothelial Cells

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Branka Vulesevic ◽  
Brian McNeill ◽  
Ferdinando Giacco ◽  
Michael Brownlee ◽  
Ross Milne ◽  
...  
Keyword(s):  
Heart Failure ◽  
Endothelial Cells ◽  
Heart Function ◽  
Capillary Density ◽  
Tunel Staining ◽  
Diabetic Mice ◽  
Over Expression ◽  
Tnf Α

Dicarbonyl stress (DS) caused by the accumulation of α-oxoaldehyde metabolites, like methylglyoxal (MG), leads to detrimental DNA and protein modifications. Under normal conditions, MG is detoxified by glyoxalase-1 (GLO1) and -2 enzymes, but this system fails in diabetes. While the role of DS in diabetic cardiomyopathy through changes in cardiomyocyte function has been well described, this study aimed to link DS with the development of endothelial dysfunction (ED) and early heart failure in diabetes. Transgenic mice that over-express GLO1 in endothelial cells (ECs) but not in cardiomyocytes, and their wild-type (WT) littermates were treated with STZ to induce hyperglycemia (WT-diabetic and GLO1-diabetic mice) or vehicle (non-diabetic controls). Hyperglycemia increased the circulating levels of ED markers in WT-diabetic (E-selectin 1.5-fold, ICAM 1.4-fold, and VCAM 1.1-fold), but not GLO1-diabetic mice. The number of vWF+ ECs in WT-diabetic hearts was reduced 2-fold compared to other groups, whereas GLO1 over-expression preserved capillary density. Cell death, determined by TUNEL staining, was greater in the hearts of WT-diabetic mice compared to all other groups. GLO1 over-expression resulted in reduced inflammation: TNF-α protein expression was increased in both diabetic groups (≥2-fold), but significantly less so in GLO1-diabetic mice (p=0.03). The preservation of ECs in GLO1-diabetic mice was associated with delayed signs of heart failure. At 4wk of hyperglycemia, WT-diabetic mice had reduced heart function compared to all other groups (p=0.04). At 8wk, cardiac function in GLO-diabetic mice was greater than in WT-diabetic mice, but both were reduced compared to non-diabetic controls (p=0.02; p=0.4). A possible mechanism for EC survival in GLO1 mice despite the presence of inflammation was examined in vitro using human aortic ECs. ECs exposed to high glucose or MG for 24h had increased apoptosis induced by TNF-α compared to cells treated only with TNF-α (by 2- and 3-fold, respectively), suggesting that reduced MG protects ECs from TNF-α mediated death. Taken together, these results suggest that DS in diabetes increases inflammation and ED, leading to the loss of ECs in the heart, which contributes to the development of heart failure.

MiR-485-5p Promotes Neuron Survival through Mediating Rac1/Notch2 Signaling Pathway after Cerebral Ischemia/Reperfusion

2020 ◽  
Vol 17 (3) ◽  
pp. 259-266 ◽  
Author(s):  
Xuan Chen ◽  
Sumei Zhang ◽  
Peipei Shi ◽  
Yangli Su ◽  
Dong Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Viability ◽  
Therapeutic Option ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Small Gtpase ◽  
Luciferase Reporter ◽  
Pathological Feature ◽  
In Cells

Objective: Ischemia-reperfusion (I/R) injury is a pathological feature of ischemic stroke. This study investigated the regulatory role of miR-485-5p in I/R injury. Methods: SH-SY5Y cells were induced with oxygen and glucose deprivation/reoxygenation (OGD/R) to mimic I/R injury in vitro. Cells were transfected with designated constructs (miR-485- 5p mimics, miR-485-5p inhibitor, lentiviral vectors overexpressing Rac1 or their corresponding controls). Cell viability was evaluated using the MTT assay. The concentrations of lactate dehydrogenase, malondialdehyde, and reactive oxygen species were detected to indicate the degree of oxidative stress. Flow cytometry and caspase-3 activity assay were used for apoptosis assessment. Dual-luciferase reporter assay was performed to confirm that Rac family small GTPase 1 (Rac1) was a downstream gene of miR-485-5p. Results: OGD/R resulted in decreased cell viability, elevated oxidative stress, increased apoptosis, and downregulated miR-485-5p expression in SH-SY5Y cells. MiR-485-5p upregulation alleviated I/R injury, evidenced by improved cell viability, decreased oxidative markers, and reduced apoptotic rate. OGD/R increased the levels of Rac1 and neurogenic locus notch homolog protein 2 (Notch2) signaling-related proteins in cells with normal miR-485-5p expression, whereas miR- 485-5p overexpression successfully suppressed OGD/R-induced upregulation of these proteins. Furthermore, the delivery of vectors overexpressing Rac1 in miR-485-5p mimics-transfected cells reversed the protective effect of miR-485-5p in cells with OGD/R-induced injury. Conclusion: This study showed that miR-485-5p protected cells following I/R injury via targeting Rac1/Notch2 signaling suggest that targeted upregulation of miR-485-5p might be a promising therapeutic option for the protection against I/R injury.

scholarly journals Uric Acid, Oxidative Stress and Inflammation in Chronic Heart Failure with Reduced Ejection Fraction

2015 ◽  
Vol 23 (4) ◽  
pp. 397-406 ◽  
Author(s):  
Adriana Iliesiu ◽  
Alexandru Campeanu ◽  
Daciana Marta ◽  
Irina Parvu ◽  
Gabriela Gheorghe
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Uric Acid ◽  
Chronic Heart Failure ◽  
Ejection Fraction ◽  
Xanthine Oxidase ◽  
Left Ventricular ◽  
Paraoxonase 1 ◽  
Lv Function ◽  
The Relationship

Abstract Background. Oxidative stress (OS) and inflammation are major mechanisms involved in the progression of chronic heart failure (CHF). Serum uric acid (sUA) is related to CHF severity and could represent a marker of xanthine-oxidase activation. The relationship between sUA, oxidative stress (OS) and inflammation markers was assessed in patients with moderate-severe CHF and reduced left ventricular (LV) ejection fraction (EF). Methods. In 57 patients with stable CHF, functional NYHA class III, with EF<40%, the LV function was assessed by N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) levels and echocardiographically through the EF and E/e’ ratio, a marker of LV filling pressures. The relationship between LV function, sUA, malondialdehyde (MDA), myeloperoxidase (MPO), paraoxonase 1 (PON-1) as OS markers and high sensitivity C-reactive protein (hsCRP) and interleukin 6 (IL-6) as markers of systemic inflammation was evaluated. Results. The mean sUA level was 7.9 ± 2.2 mg/dl, and 61% of the CHF patients had hyperuricemia. CHF patients with elevated LV filling pressures (E/e’ ≥ 13) had higher sUA (8.6 ± 2.3 vs. 7.3 ± 1.4, p=0.08) and NT-proBNP levels (643±430 vs. 2531±709, p=0.003) and lower EF (29.8 ± 3.9 % vs. 36.3 ± 4.4 %, p=0.001). There was a significant correlation between sUA and IL-6 (r = 0.56, p<0.001), MDA (r= 0.49, p= 0.001), MPO (r=0.34, p=0.001) and PON-1 levels (r= −0.39, p= 0.003). Conclusion. In CHF, hyperuricemia is associated with disease severity. High sUA levels in CHF with normal renal function may reflect increased xanthine-oxidase activity linked with chronic inflammatory response.

Matrine Protects PC12 Cells Against Aβ25–35-Induced Cytotoxicity, Oxidative Stress, Inflammation, Neuronal Apoptosis and Cell Senescence

2021 ◽  
Vol 11 (9) ◽  
pp. 1691-1697
Author(s):  
Huanli Zhang ◽  
Zhen Zhang
Keyword(s):  
Oxidative Stress ◽  
Cell Viability ◽  
Pc12 Cells ◽  
Neuronal Apoptosis ◽  
Inflammatory Responses ◽  
Neuronal Damage ◽  
Cell Senescence ◽  
Tunel Staining ◽  
Elisa Assay ◽  
Amyloid A

Background and Objectives: Beta-amyloid (Aβ) has pivotal functions in the pathogenesis of Alzheimer’s Disease (AD). The main purpose of this study is to explore the protective role and possible mechanisms of matrine against Aβ25–35-induced neurotoxicity in PC12 cells. Materials and Methods: A vitro model that involved Aβ25–35-induced neuronal damage in PC12 cells was adopted in the present study. Cell viability and apoptosis of PC12 cells were determined by CCK-8 assay and TUNEL staining, respectively. Intracellular ROS levels were determined by DCFH-DA probe and levels of TNFα, IL-6 and IL-1β were assessed by ELISA assay. In addition, telomerase reverse transcriptase (TERT) levels were determined by ELISA assay and telomere lengths were examined by real-time quantitative PCR analysis to assess telomerase activities. Furthermore, vital proteins related to cell apoptosis and hallmarks of senescence were detected by western blot analysis. Results: Matrine (10, 20, 50 μg/ml) dose-dependently protected cell viability against Aβ25–35 cytotoxicity in PC12 cells. Meanwhile, matrine at 10, 20, 50 μg/ml markedly reduced ROS production and downregulated the levels of TNFα, IL-6 and IL-1β in Aβ25–35-injuried PC12 cells. The results also proved that matrine may restore telomerase activities and telomere lengths in Aβ25–35-injuried PC12 cells by inhibiting inflammatory responses and oxidative stress. Neuronal apoptosis induced by Aβ25–35 were reversed upon cotreatment with matrine. Moreover, matrine markedly mitigated Aβ25–35 induced cell senescence in a concentration-dependentmanner. Conclusion: Our findings demonstrated that matrine protected PC12 cells against Aβ25–35-induced cytotoxicity, oxidative stress, inflammation, neuronal apoptosis and cell senescence.

scholarly journals Galectin-3 as a marker and mediator of endogenous inflammation and nitrosylation oxidative stress in patients with chronic heart failure

2013 ◽  
pp. 45-49 ◽  
Author(s):  
Yu. B. Shchukin ◽  
I. I. Berezin ◽  
E. A. Medvedeva ◽  
E. I. Seleznev ◽  
V. A. Dyachkov ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Chronic Heart Failure ◽  
Galectin 3

scholarly journals MiR-144-3p Aggravated Cartilage Injury in Rheumatoid Arthritis by Regulating BMP2/PI3K/Akt Axis

2021 ◽  
Author(s):  
Mei-Li Mo ◽  
Jin-Mei Jiang ◽  
Xiao-Ping Long ◽  
Li-Hu Xie
Keyword(s):  
Extracellular Matrix ◽  
Cell Viability ◽  
Cell Injury ◽  
Tissue Injury ◽  
Cartilage Injury ◽  
Luciferase Assay ◽  
Tunel Staining ◽  
Western Blots

Abstract Objectives Present study aimed to illustrate the role of miR-144-3p in RA. Methods N1511 chondrocytes were stimulated by IL-1β to mimic RA injury model in vitro. Rats were subjected to injection of type II collagen to establish an in vivo RA model and the arthritis index score was calculated. Cell viability was determined by CCK-8. The expression of cartilage extracellular matrix proteins (Collagen II and Aggrecan) and matrix metalloproteinases protein (MMP-13) were determined by qRT-PCR and western blots. Cell apoptosis was measured by Flow cytometry. ELISA was applied to test the secretion of pro-inflammatory cytokines (IL-1β and TNF-α). Tissue injury and apoptosis were detected by HE staining and TUNEL staining. Interaction of miR-144-3p and BMP2 was verified by dual luciferase assay. Results MiR-144-3p was dramatically increased in IL-1β induced N1511 cells. MiR-144-3p depletion elevated cell viability, suppressed apoptosis, pro-inflammatory cytokine releasing, and extracellular matrix loss in IL-1β induced N1511 cells. Moreover, miR-144-3p targeted BMP2 to modulate its expression negatively. Activation of PI3K/Akt signaling compromised inhibition of BMP2 induced aggravated N1511 cell injury with IL-1β stimulation. Inhibition of miR-144-3p alleviated cartilage injury and inflammatory in RA rats. Conclusion Collectively, miR-144-3p could aggravate chondrocytes injury inflammatory response in RA via BMP2/PI3K/Akt axis.

scholarly journals Nutritional intake and oxidative stress in chronic heart failure

2012 ◽  
Vol 22 (4) ◽  
pp. 376-382 ◽  
Author(s):  
C.M. Hughes ◽  
J.V. Woodside ◽  
C. McGartland ◽  
M.J. Roberts ◽  
D.P. Nicholls ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Chronic Heart Failure ◽  
Nutritional Intake ◽  
And Oxidative Stress
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