scholarly journals ALDH2 Inhibition Potentiates High Glucose Stress-Induced Injury in Cultured Cardiomyocytes

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Guodong Pan ◽  
Mandar Deshpande ◽  
Rajarajan A. Thandavarayan ◽  
Suresh Selvaraj Palaniyandi
Keyword(s):  
Lipid Peroxidation ◽  
High Glucose ◽  
Mitochondrial Membrane ◽  
Adduct Formation ◽  
Ctrl Group ◽  
H9c2 Cardiomyocytes ◽  
Cellular Dysfunction ◽  
Cultured Cardiomyocytes ◽  
Aldh Gene ◽  
Reactive Aldehyde

Aldehyde dehydrogenase (ALDH) gene superfamily consists of 19 isozymes. They are present in various organs and involved in metabolizing aldehydes that are biologically generated. For instance, ALDH2, a cardiac mitochondrial ALDH isozyme, is known to detoxify 4-hydroxy-2-nonenal, a reactive aldehyde produced upon lipid peroxidation in diabetic conditions. We hypothesized that inhibition of ALDH leads to the accumulation of unmetabolized 4HNE and consequently exacerbates injury in cells subjected to high glucose stress. H9C2 cardiomyocyte cell lines were pretreated with 10 μM disulfiram (DSF), an inhibitor of ALDH2 or vehicle (DMSO) for 2 hours, and then subjected to high glucose stress {33 mM D-glucose (HG) or 33 mM D-mannitol as an osmotic control (Ctrl)} for 24 hrs. The decrease in ALDH2 activity with DSF pretreatment was higher in HG group when compared to Ctrl group. Increased 4HNE adduct formation with DSF pretreatment was higher in HG group compared to Ctrl group. Pretreatment with DSF leads to potentiated HG-induced cell death in cultured H9C2 cardiomyocytes by lowering mitochondrial membrane potential. Our results indicate that ALDH2 activity is important in preventing high glucose induced cellular dysfunction.

scholarly journals Sevoflurane Postconditioning Attenuates Hypoxia/Reoxygenation Injury of Cardiomyocytes Under High Glucose by Regulating HIF-1α/MIF/AMPK Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Haiping Ma ◽  
Yongjie Li ◽  
Tianliang Hou ◽  
Jing Li ◽  
Long Yang ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Protective Effect ◽  
Cell Viability ◽  
Mrna Expression ◽  
High Glucose ◽  
Mitochondrial Membrane ◽  
Ampk Signaling ◽  
H9c2 Cardiomyocytes ◽  
Reoxygenation Injury ◽  
Hypoxia Reoxygenation

Subject: Cardiovascular disease, as a very common and serious coexisting disease in diabetic patients, and is one of the risk factors that seriously affect the prognosis and complications of surgical patients. Previous studies have shown that sevoflurane post-conditioning (SPostC) exerts a protective effect against myocardial ischemia/reperfusion injury by HIF-1α, but the protective effect is weakened or even disappeared under hyperglycemia. This study aims to explore whether regulating the HIF-1α/MIF/AMPK signaling pathway can restore the protective effect and reveal the mechanism of SPostC on cardiomyocyte hypoxia/reoxygenation injury under high glucose conditions.Methods: H9c2 cardiomyocytes were cultured in normal and high-concentration glucose medium to establish a hypoxia/reoxygenation (H/R) injury model of cardiomyocytes. SPostC was performed with 2.4% sevoflurane for 15 min before reoxygenation. Cell damage was determined by measuring cell viability, lactate dehydrogenase activity, and apoptosis; Testing cell energy metabolism by detecting reactive oxygen species (ROS) generation, ATP content and mitochondrial membrane potential; Analysis of the change of HIF-1α, MIF and AMPKα mRNA expression by RT-PCR. Western blotting was used to examine the expression of HIF-1α, MIF, AMPKα and p-AMPKα proteins. HIF-1α and MIF inhibitors and agonists were administered 40 min before hypoxia.Results: 1) SPostC exerts a protective effect by increasing cell viability, reducing LDH levels and cell apoptosis under low glucose (5 μM) after undergoing H/R injury; 2) High glucose concentration (35 μM) eliminated the cardioprotective effect of SPostC, which is manifested by a significantly decrease in the protein and mRNA expression level of the HIF-1α/MIF/AMPK signaling pathway, accompanied by decreased cell viability, increased LDH levels and apoptosis, increased ROS production, decreased ATP synthesis, and decreased mitochondrial membrane potential; 3. Under high glucose (35 μM), the expression levels of HIF-1α and MIF were up-regulated by using agonists, which can significantly increase the level of p-AMPKα protein, and the cardioprotective effect of SPostC was restored.Conclusion: The signal pathway of HIF-1α/MIF/AMPK of H9c2 cardiomyocytes may be the key point of SPostC against H/R injure. The cardioprotective of SPostC could be restored by upregulating the protein expression of HIF-1α and MIF under hyperglycemia.

MicroRNA-34a regulates high glucose-induced apoptosis in H9c2 cardiomyocytes

2013 ◽  
Vol 33 (6) ◽  
pp. 834-839 ◽  
Author(s):  
Fang Zhao ◽  
Bo Li ◽  
Yin-zhi Wei ◽  
Bin Zhou ◽  
Han Wang ◽  
...  
Keyword(s):  
High Glucose ◽  
H9c2 Cardiomyocytes ◽  
Induced Apoptosis

Evidence for a defective mitochondrial membrane in 1,2-dimethylhydrazine-induced colon adenocarcinoma in rat: Enhanced lipid peroxidation potential in vitro

1980 ◽  
Vol 9 (3) ◽  
pp. 237-244 ◽  
Author(s):  
R.S. Rana ◽  
R.H. Stevens ◽  
L. Oberley ◽  
D.P. Loven ◽  
J.M. Graves ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Mitochondrial Membrane ◽  
Colon Adenocarcinoma

scholarly journals Lipid peroxidation dominates the chemistry of DNA adduct formation in a mouse model of inflammation

2007 ◽  
Vol 28 (8) ◽  
pp. 1807-1813 ◽  
Author(s):  
Bo Pang ◽  
Xinfeng Zhou ◽  
Hongbin Yu ◽  
Min Dong ◽  
Koli Taghizadeh ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Mouse Model ◽  
Adduct Formation ◽  
Dna Adduct

scholarly journals High glucose promotes apoptosis and autophagy of MC3T3-E1 osteoblasts

2020 ◽  
Author(s):  
Pei Zhang ◽  
Jing Liao ◽  
Xiaoju Wang ◽  
Zhengping Feng
Keyword(s):  
Reactive Oxygen Species ◽  
High Glucose ◽  
Mitochondrial Membrane ◽  
Metabolic Diseases ◽  
Reactive Oxygen ◽  
Intracellular Reactive Oxygen Species ◽  
Control Group ◽  
Oxygen Species ◽  
Glucose Fluctuation ◽  
High Glucose Group

IntroductionDiabetes and osteoporosis are common metabolic diseases. Abnormal high glucose can lead to the apoptosis of osteoblasts. Autophagy is a highly conserved cellular process that degrades proteins or organelles. In the present study, we comparatively analyzed the effects of high glucose and glucose fluctuation on apoptosis and autophagy of MC3T3-E1 osteoblasts.Material and methodsMC3T3-E1 cells were respectively treated with different concentrations of D-glucose: 5.5 mM for the control group, 25 mM for the high glucose group and 5.5/25 mM for the glucose fluctuation group.ResultsHigh glucose and glucose fluctuation decreased MC3T3-E1 proliferation and activated autophagy. Also, high glucose and glucose fluctuation might induce the production of reactive oxygen species, decline the mitochondrial membrane potential and trigger apoptosis. The differences in the glucose fluctuation treatment group were more significant. Moreover, N-acetylcysteine, an antioxidant reagent, dramatically eliminated the intracellular reactive oxygen species induced by high glucose and glucose fluctuation, and significantly inhibited the autophagy and apoptosis in MC3T3-E1 osteoblasts. Furthermore, treatment with chloroquine, an inhibitor of autophagy, significantly increased the apoptosis of MC3T3-E1 osteoblasts.ConclusionsHigh glucose, especially high glucose fluctuation, inhibits proliferation and promotes apoptosis and autophagy of MC3T3-E1 osteoblasts. This may occur through inducing oxidative stress and mitochondrial damage in the osteoblasts.

Effect of miRNA-223-3p Targeting Stromal Interaction Molecule 1 on Proliferation and Apoptosis of Hypoxia/Reoxygenation-Applied H9c2 Cardiomyocytes

2021 ◽  
Vol 11 (6) ◽  
pp. 1066-1072
Author(s):  
Bin Guang ◽  
Xiaoqin Liu ◽  
Tingchen Liang
Keyword(s):  
Cell Activity ◽  
Luciferase Reporter ◽  
Cardiomyocyte Proliferation ◽  
Luciferase Reporter Gene ◽  
Luciferase Reporter Gene Assay ◽  
Gene Assay ◽  
Proliferation And Apoptosis ◽  
H9c2 Cardiomyocytes ◽  
Cultured Cardiomyocytes ◽  
Hypoxia Reoxygenation

This study was established to determine the effect of miRNA-223-3p on the proliferation and apoptosis of hypoxia/reoxygenation-applied H9c2 cardiomyocytes and the associated mechanisms. A hypoxia/reoxygenation (H/R) model was established, with normal cells also used as a control. miRNA-NC, miRNA-223-3p, anti-miRNA-NC, and anti-miRNA-223-3p plasmids were transfected into normally cultured cardiomyocytes, defined as the miRNA-NC, miRNA-223-3p, anti-miRNA-NC, and anti-miRNA-223-3p groups. In addition, miRNA-223-3p was co-transfected into normally cultured cardiomyocytes with pcDNA3.1 and pcDNA3.1-STIM1 plasmids, followed by treatment with H/R for cells in the miR-NC and miR-223-3p groups, defined as the H/R+miRNA-NC, H/R+miRNA-223-3p, H/R+miRNA-223-3p+pcDNA3.1, and H/R+miRNA-223-3p+pcDNA3.1-STIM1 groups. A liposome method was adopted for assessing transfection. qRT-PCR was used to detect miRNA-223-3p expression, while western blotting was used to detect protein expression. MTT assay was used to detect cell viability, flow cytometry to detect apoptosis, and dual luciferase reporter gene assay to detect fluorescence activity. After H/R treatment, miR-223-3p, cyclin D1, and Bcl-2 expression of cardiomyocytes decreased, p21 and Bax expression significantly increased, cell activity decreased, and the apoptosis rate increased. miRNA-223-3p achieved the targeted regulation of STIM1 expression. miRNA-223-3p overexpression promoted the H/R-induced cardiomyocyte proliferation and inhibited cardiomyocyte apoptosis. STIM1 overexpression reversed the proliferation-promoting and apoptosis-inhibiting effects of miRNA-223-3p on cardiomyocytes treated with H/R. The findings show that miRNA-223-3p overexpression promotes H/R-induced cell proliferation, inhibits apoptosis, and protects H/R-induced cardiomyocytes from injury, via a mechanism probably associated with STIM1 expression. miRNA-223-3p thus provides a new target for treating cardiomyocyte injury.

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