scholarly journals CD38 Deficiency Protects Heart from High Fat Diet-Induced Oxidative Stress Via Activating Sirt3/FOXO3 Pathway

2018 ◽  
Vol 48 (6) ◽  
pp. 2350-2363 ◽  
Author(s):  
Ling-Fang Wang ◽  
Cong-Cong Huang ◽  
Yun-Fei Xiao ◽  
Xiao-Hui Guan ◽  
Xiao-Nv Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Fat Diet ◽  
Target Genes ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
H9c2 Cell ◽  
Ros Production ◽  
High Fat ◽  
Sod Activity ◽  
Heart Injury

Background/Aims: Previous studies showed that CD38 deficiency protected heart from ischemia/reperfusion injury and high fat diet (HFD)-induced obesity in mice. However, the role of CD38 in HFD-induced heart injury remains unclear. In the present study, we have investigated the effects and mechanisms of CD38 deficiency on HFD-induced heart injury. Methods: The metabolites in heart from wild type (WT) and CD38 knockout (CD38-/-) mice were examined using metabolomics analysis. Cell viability, lactate hydrogenase (LDH) release, super oxide dismutase (SOD) activity, reactive oxygen species (ROS) production, triglyceride concentration and gene expression were examined by biochemical analysis and QPCR. Results: Our results revealed that CD38 deficiency significantly elevated the intracellular glutathione (GSH) concentration and GSH/GSSG ratio, decreased the contents of free fatty acids and increased intracellular NAD+ level in heart from CD38-/- mice fed with HFD. In addition, in vitro knockdown of CD38 significantly attenuated OA-induced cellular injury, ROS production and lipid synthesis. Furthermore, the expression of mitochondrial deacetylase Sirt3 as well as its target genes FOXO3 and SOD2 were markedly upregulated in the H9C2 cell lines after OA stimulation. In contrast, the expressions of NOX2 and NOX4 were significantly decreased in the cells after OA stimulation. Conclusion: Our results demonstrated that CD38 deficiency protected heart from HFD-induced oxidative stress via activating Sirt3/FOXO3-mediated anti-oxidative stress pathway.

scholarly journals Cabbage (Brassica oleracea var. capitata) Protects against H2O2-Induced Oxidative Stress by Preventing Mitochondrial Dysfunction in H9c2 Cardiomyoblasts

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Dong Kwon Yang
Keyword(s):  
Oxidative Stress ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Mitogen Activated Protein Kinase ◽  
Ros Production ◽  
Hepatic Diseases ◽  
Mitochondrial Functions ◽  
Wide Range ◽  
H9c2 Cardiomyoblasts ◽  
Cabbage Extract

Oxidative stress plays an important role in the progression of cardiac diseases, including ischemia/reperfusion injury, myocardial infarction, and heart failure. Growing evidence indicates that cabbage has various pharmacological properties against a wide range of diseases, such as cardiovascular diseases, hepatic diseases, and cancer. However, little is known about its effects on oxidative stress in cardiomyocytes or the underlying mechanisms. Therefore, the present study examined the effects of cabbage extract on oxidative stress in H9c2 cardiomyoblasts. Cell viability, reactive oxygen species (ROS) production, apoptosis, mitochondrial functions, and expression levels of mitogen-activated protein kinase (MAPK) proteins were analyzed to elucidate the antioxidant effects of this extract. Cabbage extract protected against H2O2-induced cell death and did not elicit any cytotoxic effects. In addition, cabbage extract suppressed ROS production and increased expression of antioxidant proteins (SOD-1, catalase, and GPx). Cabbage extract also inhibited apoptotic responses and activation of MAPK proteins (ERK1/2, JNK, and p-38) in oxidative stress-exposed H9c2 cells. Notably, cabbage extract preserved mitochondrial functions upon oxidative stress. These findings reveal that cabbage extract protects against oxidative stress and suggest that it can be used as an alternative therapeutic strategy to prevent the oxidative stress in the heart.

scholarly journals High-Fat Diet Increased Oxidative Stress and Mitochondrial Dysfunction Induced by Renal Ischemia-Reperfusion Injury in Rat

2021 ◽  
Vol 12 ◽  
Author(s):  
Priyanka N. Prem ◽  
Gino A. Kurian
Keyword(s):  
Oxidative Stress ◽  
Renal Function ◽  
Mitochondrial Dysfunction ◽  
High Fat Diet ◽  
Ischemia Reperfusion ◽  
Protein Translation ◽  
Renal Ischemia ◽  
High Fat ◽  
Dietary Regimen ◽  
The Impact

Renal ischemia-reperfusion (IR) injury is one of the major causes of acute kidney injury influenced by the ischemic duration and the presence of comorbidities. Studies have reported that high-fat diet consumption can induce renal lipotoxicity and metabolic dyshomeostasis that can compromise the vital functions of kidney. This study aimed to evaluate the impact of a high-fat diet in the recovery of renal tissue from IR and explored the cellular pathology. In this study, 24 male Wistar rats were divided into two groups: normal diet (ND; n = 12) and high-fat diet (HD; n = 12), which were further subdivided into sham and IR groups at the end of the dietary regimen. The high-fat diet was introduced in 4-week-old rats and continued for 16 weeks. IR was induced by bilateral clamping of the renal peduncle for 45 min, followed by 24 h of reperfusion. Blood chemistry, estimated glomerular filtration rate (eGFR), mitochondrial function, and oxidative stress analysis were carried out to study the pathological changes. The rats fed with HD showed a decreased eGFR and elevated plasma creatinine, thereby compromised kidney function. Subcellular level changes in HD rats are deceased mitochondrial copy number, low PGC-1α gene expression, and declined electron transport chain (ETC) enzymes and adenosine triphosphate (ATP) level. Upon IR induction, HD rats exhibited severely impaired renal function (eGFR-0.09 ml/min) and elevated injury markers compared with ND rats. A histological analysis displayed increased tubular necrosis and cast formation in HD-IR in comparison to ND-IR. The oxidative stress and mitochondrial dysfunction were more prominent in HD-IR. In vitro protein translation assessment revealed impaired translational capacity in HD-IR mitochondria, which suggests mitochondrial changes with diet that may adversely affect the outcome of IR injury. High-fat diet consumption alters the normal renal function by modifying the cellular mitochondria. The renal changes compromise the ability of the kidney to recover from ischemia during reperfusion.

Abstract 19446: Role of miR-181 Family in the Heart: A Tale of Two Intracellular Compartments

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Samarjit Das ◽  
Mark J Kohr ◽  
Brittany Dunkerly ◽  
Djahida Bedja ◽  
Oliver A Kent ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Health ◽  
Ischemia Reperfusion Injury ◽  
Isolated Heart ◽  
Ischemia Reperfusion ◽  
Mitochondrial Gene ◽  
Cardiac Injury ◽  
Ros Production ◽  
Rna Molecules ◽  
Intracellular Compartments

Recent reports suggest that mi(cro)RNAs, non-coding RNAs, can regulate numerous human genes. miRNAs play an important role in physiologic and pathologic processes of cardiovascular health. We identified a nuclear encoded miRNA (miR-181c) that translocates into mitochondria to regulate a mitochondrial gene, and ultimately affects mitochondrial function. To investigate how miR-181c leads to cardiac injury, we designed miR-181-sponges, RNA molecules with ten repeated complimentary miR-181 “seed” sequences, and generated a set of stable-H9c2 cells by transfecting either a scrambled- or the miR-181-sponge-sequences. Sponge-H9c2 showed a significant decrease in ROS production and reduced basal mitochondrial respiration, and significant protection against Doxorubicin-induced oxidative stress. However, chronic down-regulation of the entire miR-181 family also stimulates PTEN expression, and thus the sponge decreased PI3K signaling. Thus, protection against Doxorubicin is enhanced when we treated sponge-H9c2 with siRNA against PTEN. We hypothesize that miR-181a/b targets PTEN in the cytosol and miR-181c targets mt-COX1 in the mitochondria. To extend this finding, miR-181a/b-/- and miR-181c/d-/- mice were used. miR-181a/b-/- shows a significant decrease in cardiac function at baseline compared to both miR-181c/d-/- and WT groups. Basal mitochondrial ROS production was significantly decreased in miR-181c/d-/- compare to WT or miR-181a/b-/-. Using both Electron Microscopy and light-scattering at 540 nm by isolated heart mitochondria, we found that the mitochondria are smaller in the miR-181c/d-/- , and genomic DNA-qPCR showed the number of mitochondria was markedly higher in the miR-181c/d-/- heart compared to the WT or 181a/b-/- groups. miR-181c/d-/- showed a significant decrease, while miR-181a/b-/- showed a significant increase in infarct size compared to WT, when the hearts were challenged with ischemia-reperfusion injury. Taken together, the miR-181 family regulates important signaling pathways in oxidative stress, notably with detrimental results by targeting mt-COX1 (miR-181c), or with protection by targeting PTEN (miR-181a/b).

Abstract 519: Endothelin-1-Induced Oxidative Stress and Inflammatory Cell Infiltration Play a Role in High-Fat Diet Induced-Atherosclerosis in Apolipoprotein E Knockout Mice

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Melissa W Li ◽  
Pierre Paradis ◽  
Ernesto L Schiffrin
Keyword(s):  
Oxidative Stress ◽  
T Cell ◽  
Apolipoprotein E ◽  
High Fat Diet ◽  
Cell Infiltration ◽  
Ros Production ◽  
High Fat ◽  
T Cell Infiltration ◽  
Atherosclerotic Lesions ◽  
Perivascular Fat

Background: Endothelin (ET)-1 plays an important role in generation of reactive oxygen species (ROS) and inflammation in the vasculature. ET-1has been implicated in the pathogenesis of atherosclerosis since plasma and tissue ET-1 are increased in human and animal models of atherosclerosis. We observed that ET-1 overexpression exacerbates high-fat diet (HFD)-induced atherosclerosis in apolipoprotein E knockout ( apoE -/- ) mice. We hypothesized that ET-1-induced ROS and inflammation contribute to the development of atherosclerosis. Design and methods: Eight-week-old male transgenic mice overexpressing preproET-1 in the endothelium (eET-1), apoE -/- , eET-1/ apoE -/- and wild type mice were fed a HFD for 8 weeks. Aortic atherosclerotic lesions were quantified using Oil Red O staining. ROS production using dihydroethidium staining and monocyte/macrophage and T cell infiltration using immunofluorescence with MOMA-2 and anti-CD4 antibodies, respectively, were determined in perivascular fat, media and plaque in ascending aortic sections. Results: eET-1/ apoE -/- presented 3.8-fold more atherosclerotic lesions in whole aorta compared to apoE -/- ( P <0.01). ET-1 overexpression caused 2.6-, 1.9- and 1.9-fold increase in ROS production in perivascular fat, media and plaque of apoE -/- , respectively ( P <0.05). ET-1 overexpression increased monocyte/macrophage infiltration by 5- and 8-fold in perivascular fat and media, respectively ( P <0.05). CD4 + T cell infiltration was observed in perivascular fat and plaque of 3 and 5 of 6 eET-1/ apoE -/- compared to 0 and 1 of 6 apoE -/- , respectively ( P <0.05). Conclusions: These results suggest that ET-1 play an important role in progression of atherosclerotic lesions by increasing the oxidative stress and monocyte/macrophage and T cell infiltration in the atherosclerotic aorta, including the perivascular fat.

High fat diet reduces the expression of miRNA‐29b in heart and increases susceptibility of myocardium to ischemia/reperfusion injury

2018 ◽  
Vol 234 (6) ◽  
pp. 9399-9407 ◽  
Author(s):  
Elaine Castilho Guedes ◽  
Ivson Bezerra da Silva ◽  
Vanessa Morais Lima ◽  
Juliane B. Miranda ◽  
Rudá P. Albuquerque ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
High Fat Diet ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
High Fat

scholarly journals The Impact of High-Fat Diet on Mitochondrial Function, Free Radical Production, and Nitrosative Stress in the Salivary Glands of Wistar Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Anna Zalewska ◽  
Dominika Ziembicka ◽  
Małgorzata Żendzian-Piotrowska ◽  
Mateusz Maciejczyk
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
High Fat Diet ◽  
Wistar Rats ◽  
Nitrosative Stress ◽  
Ros Production ◽  
Parotid Glands ◽  
High Fat ◽  
Free Radical Production ◽  
Radical Production

Oxidative stress plays a crucial role in the salivary gland dysfunction in insulin resistance; however, the cause of increased free radical formation in these conditions is still unknown. Therefore, the aim of the study was to investigate the effect of high-fat diet (HFD) on the mitochondrial respiratory system, prooxidant enzymes, ROS production, and nitrosative/oxidative stress in the submandibular and parotid glands of rats. The experiment was performed on male Wistar rats divided into two groups (n=10): control and HFD. The 8-week feeding of HFD affects glucose metabolism observed as significant increase in plasma glucose and insulin as well as HOMA-IR as compared to the control rats. The activity of mitochondrial Complex I and Complex II+III was significantly decreased in the parotid and submandibular glands of HFD rats. Mitochondrial cytochrome c oxidase (COX) activity and the hydrogen peroxide level were significantly increased in the parotid and submandibular glands of the HFD group as compared to those of the controls. HFD rats also showed significantly lower reduced glutathione (GSH) and reduced : oxidized glutathione (GSH : GSSG) ratio, as well as a higher GSSG level in the parotid glands of HFD rats. The activity of NADPH oxidase, xanthine oxidase, and levels of oxidative/nitrosative stress (malonaldehyde, nitric oxide, nitrotyrosine, and peroxynitrite) and inflammation/apoptosis (interleukin-1βand caspase-3) biomarkers were statistically elevated in the HFD group in comparison to the controls. HFD impairs mitochondrial function in both types of salivary glands by enhancing ROS production, as well as stimulating inflammation and apoptosis. However, free radical production, protein nitration, and lipid peroxidation were more pronounced in the parotid glands of HFD rats.

Up-regulation of CTRP12 ameliorates hypoxia/re-oxygenation-induced cardiomyocyte injury by inhibiting apoptosis, oxidative stress, and inflammation via the enhancement of Nrf2 signaling

2021 ◽  
pp. 096032712110218
Author(s):  
Ai-Ping Jin ◽  
Qian-Rong Zhang ◽  
Cui-Ling Yang ◽  
Sha Ye ◽  
Hai-Juan Cheng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Target Genes ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Artery Disease ◽  
Myocardial Ischemia Reperfusion

C1q/TNF-related protein 12 (CTRP12) has been reported to play a key role in coronary artery disease. However, whether CTRP12 plays a role in the regulation of myocardial ischemia-reperfusion injury is not fully understood. The goals of this work were to assess the possible relationship between CTRP12 and myocardial ischemia-reperfusion injury. Here, we exposed cardiomyocytes to hypoxia/re-oxygenation (H/R) to establish an in vitro cardiomyocyte injury model of myocardial ischemia-reperfusion injury. Our results showed that H/R treatment resulted in a decrease in CTRP12 expression in cardiomyocytes. The up-regulation of CTRP12 ameliorated H/R-induced cardiomyocyte injury via the down-regulation of apoptosis, oxidative stress, and inflammation. In contrast, the knockdown of CTRP12 enhanced cardiomyocyte sensitivity to H/R-induced cardiomyocyte injury. Further investigation showed that CTRP12 enhanced the levels of nuclear Nrf2 and increased the expression of Nrf2 target genes in cardiomyocytes exposed to H/R. However, the inhibition of Nrf2 markedly diminished CTRP12-overexpression-mediated cardioprotective effects against H/R injury. Overall, these data indicate that CTRP12 protects against H/R-induced cardiomyocyte injury by inhibiting apoptosis, oxidative stress, and inflammation via the enhancement of Nrf2 signaling. This work suggests a potential role of CTRP12 in myocardial ischemia-reperfusion injury and proposes it as an attractive target for cardioprotection.

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