Estradiol abolishes reduction in cell death by the opioid agonist Met5-enkephalin after oxygen glucose deprivation in isolated cardiomyocytes from both sexes

2008 ◽  
Vol 295 (1) ◽  
pp. H409-H415 ◽  
Author(s):  
Matthias J. Merkel ◽  
Lijuan Liu ◽  
Zhiping Cao ◽  
William Packwood ◽  
Patricia D. Hurn ◽  
...  
Keyword(s):  
Cell Death ◽  
Estrogen Receptor ◽  
Cell Survival ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Dependent Manner ◽  
Opioid Agonist ◽  
Independent Manner ◽  
Increase Cell Survival

There is evidence for differences in the response to the treatment of cardiovascular disease in men and women. In addition, there are conflicting results regarding the effectiveness of pharmacologically induced protection or ischemic preconditioning in females. We investigated whether the ability of Met5-enkephalin (ME) to reduce cell death after oxygen-glucose deprivation (OGD) is influenced by the presence of 17β-estradiol (E2) in a nitric oxide (NO)- and estrogen receptor-dependent manner. On postnatal day 7 to 8, murine cardiomyocytes from wild-type or inducible NO synthase (iNOS) knockout mice were separated by sex, isolated by collagenase digestion, cultured for 24 h, and subjected to 90 min OGD and 180 min reoxygenation at 37°C ( n = 4 to 5 replicates). Cell cultures were incubated in E2 for 15 min or 24 h before OGD. ME was used to increase cell survival. Cell death was assessed by propidium iodide. More than 300 cells were examined for each treatment. Data are presented as means ± SE. As a result, in both sexes, ME-induced cell survival was lost in the presence of E2, and the ability of ME to improve cell survival was restored after treatment with the estrogen receptor antagonist ICI-182780. Furthermore, iNOS was necessary for ME to increase cell survival following OGD in vitro. We conclude that ME-induced reduction in cell death is abolished by E2 in a sex-independent manner via activation of estrogen receptors, and this interaction is dependent on iNOS.

scholarly journals Dexmedetomidine protects against oxygen-glucose deprivation/reoxygenation injury-induced apoptosis via the p38 MAPK/ERK signalling pathway

2017 ◽  
Vol 46 (2) ◽  
pp. 675-686 ◽  
Author(s):  
Ke Wang ◽  
Yuekun Zhu
Keyword(s):  
Cell Survival ◽  
P38 Mapk ◽  
Glucose Deprivation ◽  
Signalling Pathway ◽  
Cell Counting ◽  
Oxygen Glucose Deprivation ◽  
Protective Effects ◽  
N2a Cells ◽  
Induced Apoptosis

Objective To investigate the protective effects of dexmedetomidine (DEX) in oxygen-glucose deprivation/reoxygenation (OGD/R) injury, which is involved in a number of ischaemic diseases. Methods An in vitro OGD/R injury model was generated using mouse Neuro 2A neuroblastoma (N2A) cells. Different concentrations of DEX were administrated to OGD/R cells. CV-65 was used to inhibit p38 microtubule associated protein kinase/extracellular signal-regulated kinases (MAPK/ERK) signalling. Cell proliferation, cell cycle, apoptosis, and the levels of proteins related to p38 MAPK/ERK signalling and apoptosis were evaluated using Cell Counting Kit-8, flow cytometry, TdT-UTP nick end labelling and Western blot analysis, respectively. Results DEX treatment of OGD/R cells promoted cell survival and attenuated OGD/R-induced cell apoptosis. It also activated the p38 MAPK/ERK signalling pathway, increased the levels of Bcl-2, and decreased the levels of Bax and cleaved caspase-3. Treatment with the p38 MAPK/ERK inhibitor CV-65 inhibited the activation of p38 MAPK/ERK and abrogated the DEX-induced effects on cell survival and apoptosis. Conclusions DEX protects N2A cells from OGD/R-induced apoptosis via the activation of the p38 MAPK/ERK signalling pathway. DEX might be an effective agent for the treatment of ischaemic diseases.

scholarly journals ATM inhibition drives metabolic adaptation via induction of macropinocytosis

2020 ◽  
Author(s):  
Chi-Wei Chen ◽  
Raquel Buj ◽  
Erika S. Dahl ◽  
Kelly E. Leon ◽  
Erika L. Varner ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Survival ◽  
Cancer Cell ◽  
Metabolic Reprogramming ◽  
Metabolic Adaptation ◽  
Dependent Manner ◽  
Cancer Cell Survival ◽  
Branched Chain

SummaryMacropinocytosis is a nonspecific endocytic process that enhances cancer cell survival under nutrient-poor conditions. Ataxia-Telangiectasia mutated (ATM) is a tumor suppressor that plays a role in cellular metabolic reprogramming. We report that suppression of ATM increases macropinocytosis in an AMPK-dependent manner to promote cancer cell survival in nutrient-poor conditions. Combined inhibition of ATM and macropinocytosis suppressed proliferation and induced cell death both in vitro and in vivo. Metabolite analysis of the ascites and interstitial fluid from tumors indicated decreased branched chain amino acids (BCAAs) in the microenvironment of ATM-inhibited tumors. Supplementation of ATM inhibitor-treated cells with BCAAs abrogated AMPK phosphorylation and macropinocytosis and rescued the cell death that occurs due to combined inhibition of ATM and macropinocytosis. These data reveal a novel molecular basis of ATM-mediated tumor suppression whereby loss of ATM promotes pro-tumorigenic uptake of nutrients to promote cancer cell survival and reveal a metabolic vulnerability of ATM-inhibited cells.

scholarly journals Cardioprotective Effect of Propofol against Oxygen Glucose Deprivation and Reperfusion Injury in H9c2 Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Dandan Zhao ◽  
Qing Li ◽  
Qiuping Huang ◽  
Xuguang Li ◽  
Min Yin ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Underlying Mechanism ◽  
Oxygen Glucose Deprivation ◽  
H9c2 Cell ◽  
Dependent Manner ◽  
H9c2 Cells

Background. The intravenous anesthetic propofol is reported to be a cardioprotective agent against ischemic-reperfusion injury in the heart. However, the regulatory mechanism still remains unclear.Methods. In this study, we used H9c2 cell line under condition of oxygen glucose deprivation (OGD) followed by reperfusion (OGD/R) to inducein vitrocardiomyocytes ischemia-reperfusion injury. Propofol (5, 10, and 20 μM) was added to the cell cultures before and during the OGD/R phases to investigate the underlying mechanism.Results. Our data showed that OGD/R decreased cell viability, and increased lactate dehydrogenase leakage, and reactive oxygen species and malondialdehyde production in H9c2 cells, all of which were significantly reversed by propofol. Moreover, we found that propofol increased both the activities and protein expressions of superoxide dismutase and catalase. In addition, propofol increased FoxO1 expression in a dose-dependent manner and inhibited p-AMPK formation significantly.Conclusions. These results indicate that the propofol might exert its antioxidative effect through FoxO1 in H9c2 cells, and it has a potential therapeutic effect on cardiac disorders involved in oxidative stress.

scholarly journals Purification and Identification of p68 RNA Helicase Acting as a Transcriptional Coactivator Specific for the Activation Function 1 of Human Estrogen Receptor α

1999 ◽  
Vol 19 (8) ◽  
pp. 5363-5372 ◽  
Author(s):  
Hideki Endoh ◽  
Kazunori Maruyama ◽  
Yoshikazu Masuhiro ◽  
Yoko Kobayashi ◽  
Masahide Goto ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Target Genes ◽  
Retinoic Acid Receptor ◽  
Rna Helicase ◽  
Activation Function ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Cell Type ◽  
Independent Manner

ABSTRACT The estrogen receptor (ER) regulates the expression of target genes in a ligand-dependent manner. The ligand-dependent activation function AF-2 of the ER is located in the ligand binding domain (LBD), while the N-terminal A/B domain (AF-1) functions in a ligand-independent manner when isolated from the LBD. AF-1 and AF-2 exhibit cell type and promoter context specificity. Furthermore, the AF-1 activity of the human ERα (hERα) is enhanced through phosphorylation of the Ser118 residue by mitogen-activated protein kinase (MAPK). From MCF-7 cells, we purified and cloned a 68-kDa protein (p68) which interacted with the A/B domain but not with the LBD of hERα. Phosphorylation of hERα Ser118 potentiated the interaction with p68. We demonstrate that p68 enhanced the activity of AF-1 but not AF-2 and the estrogen-induced as well as the anti-estrogen-induced transcriptional activity of the full-length ERα in a cell-type-specific manner. However, it did not potentiate AF-1 or AF-2 of ERβ, androgen receptor, retinoic acid receptor alpha, or mineralocorticoid receptor. We also show that the RNA helicase activity previously ascribed to p68 is dispensable for the ERα AF-1 coactivator activity and that p68 binds to CBP in vitro. Furthermore, the interaction region for p68 in the ERα A/B domain was essential for the full activity of hERα AF-1. Taken together, these findings show that p68 acts as a coactivator specific for the ERα AF-1 and strongly suggest that the interaction between p68 and the hERα A/B domain is regulated by MAPK-induced phosphorylation of Ser118.

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