scholarly journals High-Glucose Induced Protective Effect against Hypoxic Injury Is Associated with Maintenance of Mitochondrial Membrane Potential

2003 ◽  
Vol 53 (6) ◽  
pp. 451-459 ◽  
Author(s):  
Min Hwa Kim ◽  
Yi-Sook Jung ◽  
Chang-Hyun Moon ◽  
Soo Hwan Lee ◽  
Eun Joo Baik ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Protective Effect ◽  
Mitochondrial Membrane Potential ◽  
High Glucose ◽  
Mitochondrial Membrane ◽  
Hypoxic Injury

Protective effect of the dimer of 16,16-diMePGB1 against KCN-induced mitochondrial failure in hepatocytes

1992 ◽  
Vol 263 (2) ◽  
pp. C405-C411 ◽  
Author(s):  
Y. Park ◽  
T. M. Devlin ◽  
D. P. Jones
Keyword(s):  
Membrane Potential ◽  
Protective Effect ◽  
Ion Transport ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Function ◽  
Mitochondrial Membrane ◽  
Time Dependent ◽  
Dependent Manner ◽  
Protective Effects ◽  
Cellular Swelling

The dimer and trimer of 16,16-dimethyl-15-dehydroprostaglandin B1 (16,16-diMePGB1) previously have been shown to have protective effects on mitochondrial function. To examine the potential mechanisms involved in protection against mitochondrial failure, we have studied the effects of the dimer of 16,16-diMe-PGB1 (dicalciphor) on mitochondrial function in hepatocytes exposed to KCN. Addition of micromolar concentrations of dicalciphor provided substantial protection against KCN-induced toxicity in a concentration- and time-dependent manner. Dicalciphor, however, had no effect on total or mitochondrial ATP losses in KCN-treated cells. The dimer prevented the marked loss of mitochondrial membrane potential (delta psi) and delta pH that occurs as a result of KCN treatment and prevented KCN-induced loading of phosphate in mitochondria. Furthermore, the dimer of 16,16-diMePGB1 also prevented KCN-induced mitochondrial and cellular swelling. These results demonstrate that dicalciphor protects against KCN-induced damage and that this protection is associated with regulation of specific mitochondrial ion transport functions.

scholarly journals Thrombopoietin Has Protective Effect in Neonatal Hypoxia-Ischemia Rat Model

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4898-4898
Author(s):  
Liang Li ◽  
Liuming Yang ◽  
Hongwu Xin ◽  
Beng H Chong ◽  
Mo Yang
Keyword(s):  
Membrane Potential ◽  
Protective Effect ◽  
Brain Damage ◽  
Mitochondrial Membrane Potential ◽  
Rat Model ◽  
Mitochondrial Membrane ◽  
Conflicts Of Interest ◽  
Neonatal Rat ◽  
Neural Cells ◽  
Protective Effects

Thrombopoietin (TPO) is a growth factor for the megakaryocytic lineage. The expression of TPO and TPO receptor (c-mpl) in the central nervous system (CNS) and the role of TPO in neural cells and brain damage models were investigated. Our results showed the expression of TPO in human cerebral hemisphere, cerebellum, cerebrospinal fluid and blood plasma. We found that TPO had a protective effect in hypoxic-ischemic rat model, as indicated by the increased ipsilateral brain weight and neuron density in a neonatal rat model of hypoxic-ischemic brain damage. Recoveries of sensorimotor functions and histopathology were observed in these animals that received TPO. In addition, TPO could promote C17.2 cells proliferation by activating PI3K/Akt signaling pathway, and the proliferation could be reduced to nearly basal level by the pre-treatment with LY 294002. The phosphorylation of AKT, which is a hallmark of activation of each molecule was significantly enhanced after the treatment with TPO in the cells, peaking at 30 min after stimulation with TPO. TPO was also found to have an anti-apoptotic effect which mediated via Bcl-2/BAX and suppressing the mitochondrial membrane potential. Results showed the increased level of Bcl-2 and decreased level of BAX were in the time-dependence manner (0, 5, 15, 30 and 60 mins) in these cells. In addition, the mitochondrial membrane potential was significantly decreased by adding 100 ng/ml TPO. Our results indicated that TPO have neural protective effects. Disclosures No relevant conflicts of interest to declare.

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.

scholarly journals Thrombopoietin Protects Cardiomyocytes from Iron-Overload Induced Oxidative Stress and Mitochondrial Injury

2015 ◽  
Vol 36 (5) ◽  
pp. 2063-2071 ◽  
Author(s):  
Shing Chan ◽  
Godfrey Chifung Chan ◽  
Jieyu Ye ◽  
Qizhou Lian ◽  
Jianliang Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Membrane Potential ◽  
Iron Overload ◽  
Protective Effect ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Lipid Hydroperoxides ◽  
Ros Production ◽  
H9c2 Cells ◽  
Induced Apoptosis

Background/Aims: Thalassaemia accompanied with iron-overload is common in Hong Kong. Iron-overload induced cardiomyopathy is the commonest cause of morbidity and mortality in patients with β-thalassaemia. Chronic iron-overload due to blood transfusion can cause cardiac failure. Decreased antioxidant defence and increased ROS production may lead to oxidative stress and cell injury. Iron-overload may lead to heart tissue damage through lipid peroxidation in response to oxidative stress, and a great diversity of toxic aldehydes are formed when lipid hydroperoxides break down in heart and plasma. Methods: Iron entry into embryonic heart H9C2 cells was determined by calcein assay using a fluorometer. Reactive oxygen species (ROS) production in cells treated with FeCl3 or thrombopoietin (TPO) was monitored by using the fluorescent probe H2DCFDA. Changes in mitochondrial membrane potential of H9C2 cells were quantified by using flow cytometry. Results: We demonstrated that iron induced oxidative stress and apoptosis in cardiomyocytes, and that iron increased ROS production and reduced cell viability in a dose-dependent manner. Iron treatment increased the proportion of cells with JC-1 monomers, indicating a trend of drop in the mitochondrial membrane potential. TPO exerted a cardio-protective effect on iron-induced apoptosis. Conclusions: These findings suggest that iron-overload leads to the generation of ROS and further induces apoptosis in cardiomyocytes via mitochondrial pathways. TPO might exert a protective effect on iron-overload induced apoptosis via inhibiting oxidative stress and suppressing the mitochondrial pathways in cardiomyocytes.

scholarly journals Nuclear Genome-Encoded Long Noncoding RNAs and Mitochondrial Damage in Diabetic Retinopathy

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3271
Author(s):  
Ghulam Mohammad ◽  
Renu A. Kowluru
Keyword(s):  
Diabetic Retinopathy ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
High Glucose ◽  
Mitochondrial Membrane ◽  
Noncoding Rnas ◽  
Nuclear Genome ◽  
Long Noncoding Rnas ◽  
Mitochondrial Homeostasis

Retinal mitochondria are damaged in diabetes-accelerating apoptosis of capillary cells, and ultimately, leading to degenerative capillaries. Diabetes also upregulates many long noncoding RNAs (LncRNAs), including LncMALAT1 and LncNEAT1. These RNAs have more than 200 nucleotides and no open reading frame for translation. LncMALAT1 and LncNEAT1 are encoded by nuclear genome, but nuclear-encoded LncRNAs can also translocate in the mitochondria. Our aim was to investigate the role of LncMALAT1 and LncNEAT1 in mitochondrial homeostasis. Using human retinal endothelial cells, the effect of high glucose on LncMALAT1 and LncNEAT1 mitochondrial localization was examined by RNA fluorescence in situ hybridization. The role of these LncRNAs in mitochondrial membrane potential (by JC-I staining), mtDNA integrity (by extended length PCR) and in protective mtDNA nucleoids (by SYBR green staining) was examined in MALAT1- or NEAT1-siRNA transfected cells. High glucose increased LncMALAT1 and LncNEAT1 mitochondrial expression, and MALAT1-siRNA or NEAT1-siRNA ameliorated glucose-induced damage to mitochondrial membrane potential and mtDNA, and prevented decrease in mtDNA nucleoids. Thus, increased mitochondrial translocation of LncMALAT1 or LncNEAT1 in a hyperglycemic milieu plays a major role in damaging the mitochondrial structural and genomic integrity. Regulation of these LncRNAs can protect mitochondrial homeostasis, and ameliorate formation of degenerative capillaries in diabetic retinopathy.

ATP synthase activity is required for fructose to protect cultured hepatocytes from the toxicity of cyanide

1993 ◽  
Vol 264 (3) ◽  
pp. C709-C714 ◽  
Author(s):  
J. W. Snyder ◽  
J. G. Pastorino ◽  
A. P. Thomas ◽  
J. B. Hoek ◽  
J. L. Farber
Keyword(s):  
Membrane Potential ◽  
Protective Effect ◽  
Mitochondrial Membrane Potential ◽  
Atp Synthase ◽  
Mitochondrial Membrane ◽  
Cultured Hepatocytes ◽  
Intracellular Acidosis ◽  
Mitochondrial Atp Synthase ◽  
Carbonyl Cyanide

The contributions of the loss of the mitochondrial membrane potential (MMP) and a depletion of ATP to the genesis of lethal injury were evaluated in the killing of cultured hepatocytes by cyanide (CN). The glycolytic production of ATP from fructose (Fru) maintained the MMP and prevented the killing by CN. Inhibition of the mitochondrial ATP synthase by 0.1 micrograms/ml oligomycin (Oligo) reduced ATP stores at the same rate and to the same extent as did 1 mM CN. With Oligo there was no loss of the MMP, and the hepatocytes maintained viability over the 6 h during which CN killed all of the cells. Oligo had no effect on the rate of killing by CN. However, Oligo reversed the protective effect of Fru on CN-induced killing, a result that correlated with the loss of MMP but not with the depletion of ATP. Neither Fru nor Oligo affected the intracellular acidosis achieved with CN alone. Fru also prevented toxicity of the uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP), a result that correlated with the preservation of MMP. Oligo potentiated the toxicity of CCCP. It is concluded that a functioning mitochondrial ATP synthase is required for the production of ATP from Fru to prevent the killing of hepatocytes by CN. The extent of killing correlated closely with changes in the MMP but not with changes in the content of ATP.

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