scholarly journals Exercise Capacity is Improved by Levosimendan in Heart Failure and Sarcopenia Mice via the Alleviation of Atrophy and Apoptosis of Skeletal Muscle

2021 ◽  
Author(s):  
Di Wang ◽  
Ming Song ◽  
Long-fei Shen ◽  
Lu Han ◽  
Ping Zhu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Skeletal Muscle ◽  
Membrane Potential ◽  
Cardiac Function ◽  
Mitochondrial Membrane Potential ◽  
Exercise Capacity ◽  
Stress Level ◽  
Mitochondrial Membrane ◽  
Oxidative Stress Level

Abstract Background Sarcopenia, a common complication of heart failure (HF), dramatically reduces the benefits of exercise training. Levosimendan is an effective drug for the treatment of heart failure, but its relationship with sarcopenia is still unclear. We aimed to investigate the effect of levosimendan on heart failure with sarcopenia and to explore whether levosimendan can enhance skeletal muscle contractibility, improve skeletal muscle atrophy, and thus improve exercise tolerance of individuals with heart failure.Methods C57BL6/J mice were used to establish the heart failure with sarcopenia model by ligating of the left anterior descending branch combined with hindlimb unloading and were injected of levosimendan (3mg/Kg, once a week, four times in total). Mice (n=40) were divided into control group, sham operation group, HF group, HF + solvent group, HF + levosimendan group, HF + sarcopenia group, HF + sarcopenia + solvent group, HF+ sarcopenia + levosimendan group. After the treatment, exercise capacity and cardiac function were evaluated. Serum BNP, LDH, and CK content were measured. Muscle morphology, fiber type, inflammation level, and apoptosis levels were detected by histopathological and molecular biological methods. Mitochondrial function and oxidative stress level were assessed by mitochondrial membrane potential and SOD activity.Result Levosimendan could improve EF and FS in mice with HF and sarcopenia (P<0.001) and increase their forelimb grip strength, hanging impulse, maximum running distance and time (P<0.05). After correcting for EF, the improvement of exercise capacity by levosimendan remained (P<0.05). HE staining showed that levosimendan directly increased the CSA of gastrocnemius in mice with HF and sarcopenia (P<0.001). After levosimendan injection, the proportion of slow muscle fibers increased, but this improvement of muscle fiber typing might be attributed to improved cardiac function (P>0.05). Levosimendan also maintained mitochondrial membrane potential, decreased cleaved caspase-3, cleaved caspase-9, Bax expression, and increased Bcl2 expression (P<0.05). This effect is independent of improved cardiac function. IL-6, TNF-α expression decreased and SOD activity, GSH/GSSG ratio significantly increased (P<0.05) in skeletal muscle after injection of levosimendan, improved oxidative stress level. The improvement in oxidative stress level was attributed to improved cardiac function (P>0.05).Conclusion Levosimendan reduce the loss of skeletal muscle mitochondrial membrane potential, decrease the apoptosis, alleviate the inflammation and oxidative stress, and ultimately improve the exercise capacity of mice with heart failure and sarcopenia. Therefore, levosimendan may be a potential drug for the treatment of heart failure with sarcopenia.

scholarly journals Pre-arrest hypothermia improved cardiac function of rats by ameliorating the myocardial mitochondrial injury after cardiac arrest

2019 ◽  
Vol 244 (14) ◽  
pp. 1186-1192
Author(s):  
Yuanzheng Lu ◽  
Xiaoyun Zeng ◽  
Xiaoli Jing ◽  
Meixian Yin ◽  
MMS Mary P Chang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Arrest ◽  
Membrane Potential ◽  
Survival Rate ◽  
Ventricular Fibrillation ◽  
Cardiac Function ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Left Ventricular Ejection ◽  
Mitochondrial Injury

This study investigated the effects of hypothermia induced before cardiac arrest or after return of spontaneous circulation (ROSC) on cardiac function and myocardial mitochondrial injury after ROSC in a rat cardiac arrest model. Sixty healthy, male Wistar rats were randomly divided into the Normothermia group, pre-arrest hypothermia (Pre-HT) group, and post-resuscitation hypothermia (Post-HT) group. The rats underwent 8 min of untreated ventricular fibrillation followed by cardiopulmonary resuscitation. Twelve rats in each group were used to evaluate the left ventricular ejection fraction before ventricular fibrillation and 4 h after ROSC. Survival was determined at 24 h after ROSC. The remaining eight rats in each group were used to detect for heart malondialdehyde, reduced glutathione, adenosine triphosphate levels and mitochondrial histology. Oxygen consumption rate and mitochondrial membrane potential were evaluated 4 h after ROSC; 10 of 12 rats in Pre-HT group, 5 of 12 in Post-HT group, and 6 of 12 in normothermia group were successfully resuscitated. The survival rate of each group was 66.7%, 33.3%, and 25%, respectively. Rats in the Pre-HT group showed less alteration of the mitochondrial ultrastructure and oxidative stress injury, better maintenance of adenine nucleotides, and more preservation of the mitochondrial membrane potential and respiratory function when compared with rats in the Post-HT and normothermia groups. Transient hypothermia is an effective preconditioning stimulus to induce ischemic tolerance in a cardiac arrest model and worthy of further evaluation for potential clinical use. Impact statement In this paper, we investigated the effects of hypothermia induced before ischemia or after ROSC on cardiac function, oxidative stress damage, and myocardial mitochondrial ischemia–reperfusion injury after cardiac arrest in a rat model with VF. We demonstrated that pre-arrest hypothermia conferred greater cardio-protective benefits than delayed post-resuscitation hypothermia, reduced the number of defibrillations required and dosages of epinephrine during CPR, decreased oxidative stress, ameliorated mitochondrial dysfunction, and subsequently improved survival rate.

scholarly journals Artemisinin attenuated oxidative stress and apoptosis by inhibiting autophagy in MPP+-treated SH-SY5Y cells

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Junqiang Yan ◽  
Hongxia Ma ◽  
Xiaoyi Lai ◽  
Jiannan Wu ◽  
Anran Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Membrane Potential ◽  
Protein Expression ◽  
Mitochondrial Membrane Potential ◽  
Western Blotting ◽  
Cell Apoptosis ◽  
Mitochondrial Membrane ◽  
Caspase 3 ◽  
Neuroprotective Effect ◽  
Neuroprotective Effects

Abstract Background Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. The oxidative stress is an important component of the pathogenesis of PD. Artemisinin (ART) has antioxidant and neuroprotective effects. The purpose of this study is to explore the neuroprotective effect of ART on 1-methyl-4-phenyliodine iodide (MPP +)-treated SH-SY5Y cells and underlying mechanism. Methods We used MPP+-treated SH-SY5Y cells to study the neuroprotective effect of ART. Cell viability was measured by MTT assay after incubating the cells with MPP+ and/or ART for 24 h. DCFH-DA was used to detect the level of intracellular reactive oxygen species (ROS), and WST-8 was used to detect the level of superoxide dismutase (SOD). The level of intracellular reduced glutathione (GSH) was detected with 5,5΄-dithiobis-(2-nitrobenzoic acid), and the level of malondialdehyde (MDA) was assessed based on the reaction of MDA and thiobarbituric acid. A mitochondrial membrane potential detection kit (JC-1) was used to detect changes in the mitochondrial membrane potential (MMP), and an Annexin V-FITC cell apoptosis kit was used to detect cell apoptosis. The expression levels of caspase-3, cleaved caspase-3 and the autophagy-related proteins LC3, beclin-1, and p62 were detected by Western blotting. In addition, to verify the change in autophagy, we used immunofluorescence to detect the expression of LC3 and p62. Results No significant cytotoxicity was observed at ART concentrations up to 40 μM. ART could significantly increase the viability of SH-SY5Y cells treated with MPP+ and reduce oxidative stress damage and apoptosis. In addition, the Western blotting and immunofluorescence results showed that MPP+ treatment could increase the protein expression of beclin1 and LC3II/LC3I and decrease the protein expression of p62, indicating that MPP+ treatment could induce autophagy. Simultaneous treatment with ART and MPP+ could decrease the protein expression of beclin1 and LC3II/LC3I and increase the protein expression of p62, indicating that ART could decrease the level of autophagy induced by MPP+. Conclusion Our results indicate that ART has a protective effect on MPP+-treated SH-SY5Y cells by the antioxidant, antiapoptotic activities and inhibition of autophagy. Our findings may provide new hope for the prevention and treatment of PD.

The role of mitochondrial membrane potential in ischemic heart failure

Mitochondrion ◽  
2011 ◽  
Vol 11 (5) ◽  
pp. 700-706 ◽  
Author(s):  
Bernhard Kadenbach ◽  
Rabia Ramzan ◽  
Rainer Moosdorf ◽  
Sebastian Vogt
Keyword(s):  
Heart Failure ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Ischemic Heart ◽  
Ischemic Heart Failure

scholarly journals PO-173 The Effects of Interval Exercise on oxidative stress and Smyd1-related myocardial hypertrophy in Rats with Myocardial Infarction

2018 ◽  
Vol 1 (4) ◽  
Author(s):  
Qiaoqin Liang ◽  
Mengxin Cai ◽  
Jiaqi Zhang ◽  
Zhenjun Tian
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Cardiac Function ◽  
Stress Level ◽  
Exercise Group ◽  
Control Group ◽  
Coronary Artery Ligation ◽  
Interval Exercise ◽  
Oxidative Stress Level ◽  
Sarcomere Assembly

Objective This study was carried out to investigate interval exercise on Smyd1 expression and F-actin sarcomere assembly in non-infarcted myocardium of normal and myocardial infarction(MI) rats and its possible mechanism. Methods Male SD rats were randomly divided into normal control group (C), normal interval exercise group (CE), sham-operated group (S), MI group (MI), MI with interval exercise group (ME) and MI with ROS Tempol group (MT), n=10. MI model was established by left anterior descending coronary artery ligation. Interval exercise was carried out on a small animal treadmill. MT group was given an oral solution of Tempol (2mmol/L). Hemodynamics was performed to evaluate cardiac function. HE and Masson staining were used to analyze the cross-sectional area (CSA) of cardiomyocytes and collagen volume fraction, respectively. T-SOD and MDA kits were used to detect oxidative stress. H9C2 cells were treated with H2O2. Immunofluorescence staining was used to determine Smyd1 expression and F-actin sarcomere assembly. RT-qPCR and Western blotting were used to detect the gene or protein expression of Smyd1, Trx1, Hsp90, MuRF1, cTnI, α-actinin and BNP. Results Smyd1, Trx1, Hsp90, MuRF1 and BNP expression in the peri-infarcted area were up-regulated, but cTnI and α-actinin expression and F-actin assembly were decreased. The cardiac function was reduced. Both interval exercise and Tempol intervention significantly increase the CSA and expression of Smyd1, Trx1, cTnI and α-actinin, improve the antioxidation capacity and F-actin sarcomere assembly and cardiac function, reduce the expression of Hsp90, MuRF1, BNP and ROS level, and inhibit the fibrosis of myocardium. The oxidative stress level was closely related to the Smyd1 expression. Improvement of cardiac function were correlated with Smyd1 expression. H2O2 can induce oxidative stress injuries of H9C2, and its closely related to cardiomyocytes oxidative stress level and Smyd1 expression. Conclusions Interval exercise could promote antioxidant capability and physiological cardiomyocyte hypertrophy, regulate the expression of Smyd1, Hsp90 and MuRF1 in infarcted heart; so as to improve the cardiac function. Smyd1 may participate in pathologic hypertrophy of cardiomyocytes caused by oxidative stress.

Abstract 371: Mitochondrial Antiviral Signaling (MAVS) Protects Cardiomyocytes Under Oxidative Stress by Interfering with Bax-Mediated Cell Death

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Toshitaka Yajima ◽  
Stanley Park ◽  
Hanbing Zhou ◽  
Michinari Nakamura ◽  
Mitsuyo Machida ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Membrane Potential ◽  
Cytochrome C ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Cytochrome C Release ◽  
Antiviral Signaling ◽  
Cell Death Pathway ◽  
The Impact

MAVS is a mitochondrial outer membrane protein that activates innate antiviral signaling by recognizing cytosolic viral RNAs and DNAs. While the discovery of MAVS is the first molecular evidence that links mitochondria to innate immune mechanisms, it is still unclear whether MAVS affects mitochondrial cell death as a member of caspase activation and recruitment domain (CARD)-containing proteins. We found that MAVS interacts with Bax through CARD by Yeast two-hybrid and a series of immunoprecipitation (IP) assay, which led us to hypothesize that MAVS functions not only in the innate antiviral mechanisms but also in the mitochondrial cell death pathway. Methods: 1) We examined molecular interaction between MAVS and Bax under oxidative stress by IP using isolated myocytes with H2O2 stimulation and the heart post ischemia-reperfusion (I/R). 2) We evaluated the effect of MAVS on mitochondrial membrane potential and apoptosis under H2O2 stimulation using isolated myocytes with adenoviral MAVS knockdown. 3) We investigated the impact of MAVS on %myocardial infarction (%MI) post I/R using cardiac-specific MAVS knockout (cKO) and transgenic (cTg) mice which we have originally generated. 4) We examined the effect of MAVS on recombinant Bax (rBax)-mediated cytochrome c release using isolated mitochondria from wild type (WT) and MAVS KO mice. Results: 1) The amount of Bax pulled down with MAVS was significantly increased in isolated myocytes with 0.2 mM H2O2 compared to those without stimulation (mean±SD; 1.808±0.14, n=5, p<0.001) and in the heart post I/R compared to sham (2.2±1.19, n=3, p=0.0081). 2) Myocytes with MAVS knockdown showed clear abnormalities in mitochondrial membrane potential and caspace-3 cleavage with 0.2 mM H2O2 compared to control cardiomyocytes. 3) MAVS cKO had significantly larger %MI than WT (81.9 ± 5.8% vs. 42.6 ± 13.6%, n=8, p=0.0008). In contrast, MAVS cTg had significantly smaller %MI that WT (30.0 ± 4.8% vs. 49.2 ± 4.8%, n=10, p=0.0113). 4) Mitochondria from MAVS KO exhibited cytochrome c release after incubation with 2.5 μ g of rBax while those from WT required 10 μ g of rBax. Conclusion: These results demonstrate that MAVS protects cardiomyocyte under oxidative stress by interfering with Bax-mediated cytochrome c release from mitochondria.

Melatonin and Nicotinamide Mononucleotide Attenuate Myocardial Ischemia/Reperfusion Injury via Modulation of Mitochondrial Function and Hemodynamic Parameters in Aged Rats

2019 ◽  
Vol 25 (3) ◽  
pp. 240-250 ◽  
Author(s):  
Leila Hosseini ◽  
Manouchehr S. Vafaee ◽  
Reza Badalzadeh
Keyword(s):  
Oxidative Stress ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Function ◽  
Mitochondrial Membrane ◽  
Ischemia Reperfusion ◽  
Combined Therapy ◽  
Aged Rats ◽  
Hemodynamic Parameters ◽  
Nicotinamide Mononucleotide

Ischemic heart diseases are the major reasons for disability and mortality in elderly individuals. In this study, we tried to examine the combined effects of nicotinamide mononucleotide (NMN) preconditioning and melatonin postconditioning on cardioprotection and mitochondrial function in ischemia/reperfusion (I/R) injury of aged male rats. Sixty aged Wistar rats were randomly allocated to 5 groups, including sham, control, NMN-receiving, melatonin-receiving, and combined therapy (NMN+melatonin). Isolated hearts were mounted on Langendorff apparatus and then underwent 30-minue ligation of left anterior descending coronary artery to induce regional ischemic insult, followed by 60 minutes of reperfusion. Nicotinamide mononucleotide (100 mg/kg/d intraperitoneally) was administered for every other day for 28 days before I/R. Melatonin added to perfusion solution, 5 minutes prior to the reperfusion up to 15 minutes early reperfusion. Myocardial hemodynamic and infarct size (IS) were measured, and the left ventricles samples were obtained to evaluate cardiac mitochondrial function and oxidative stress markers. Melatonin postconditioning and NMN had significant cardioprotective effects in aged rats; they could improve hemodynamic parameters and reduce IS and lactate dehydrogenase release compared to those of control group. Moreover, pretreatment with NMN increased the cardioprotection by melatonin. All treatments reduced oxidative stress and mitochondrial reactive oxygen species (ROS) levels and improved mitochondrial membrane potential and restored NAD+/NADH ratio. The effects of combined therapy on reduction of mitochondrial ROS and oxidative status and improvement of mitochondrial membrane potential were greater than those of alone treatments. Combination of melatonin and NMN can be a promising strategy to attenuate myocardial I/R damages in aged hearts. Restoration of mitochondrial function may substantially contribute to this cardioprotection.

Encircling granulosa cells protects against di-(2-ethylhexyl)phthalate-induced apoptosis in rat oocytes cultured in vitro

Zygote ◽  
2019 ◽  
Vol 27 (4) ◽  
pp. 203-213 ◽  
Author(s):  
Anima Tripathi ◽  
Vivek Pandey ◽  
A.N. Sahu ◽  
Alok K. Singh ◽  
Pawan K. Dubey
Keyword(s):  
Oxidative Stress ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Granulosa Cells ◽  
Mitochondrial Membrane ◽  
Dependent Manner ◽  
Apoptotic Markers ◽  
Induced Apoptosis ◽  
Ethylhexyl Phthalate

SummaryThe present study investigated if the presence of encircling granulosa cells protected against di(2-ethylhexyl)phthalate (DEHP)-induced oxidative stress in rat oocytes cultured in vitro. Denuded oocytes and cumulus–oocyte complexes (COCs) were treated with or without various doses of DEHP (0.0, 25.0, 50.0, 100, 200, 400 and 800 μM) in vitro. Morphological apoptotic changes, levels of oxidative stress and reactive oxygen species (ROS), mitochondrial membrane potential, and expression levels of apoptotic markers (Bcl2, Bax, cytochrome c) were analyzed. Our results showed that DEHP induced morphological apoptotic changes in a dose-dependent manner in denuded oocytes cultured in vitro. The effective dose of DEHP (400 µg) significantly (P>0.05) increased oxidative stress by elevating ROS levels and the mitochondrial membrane potential with higher mRNA expression and protein levels of apoptotic markers (Bax, cytochrome c). Encircling granulosa cells protected oocytes from DEHP-induced morphological changes, increased oxidative stress and ROS levels, as well as increased expression of apoptotic markers. Taken together our data suggested that encircling granulosa cells protected oocytes against DEHP-induced apoptosis and that the presence of granulosa cells could act positively towards the survival of oocytes under in vitro culture conditions and may be helpful during assisted reproductive technique programmes.

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