Glutathione Suppresses Cerebral Infarct Volume and Cell Death after Ischemic Injury: Involvement of FOXO3 Inactivation and Bcl2 Expression

Song, Jeong Sup; Park, Joohyun; Oh, Yumi; Lee, Jong Eun

doi:10.1155/2015/426069

Cited by 53 publications

(37 citation statements)

References 75 publications

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“…Although there are no previous studies interpreting the effect of CoQ10 on p -FOXO3A, we can assume that CoQ10 induced p -FOXO3A could be attributed to the increased phosphorylation of Akt along with the antioxidant capacity of CoQ10, proven herein and supported by the study of Song et al (2015) . These authors found that administration of GSH attenuate cerebral infarct volume in rats exposed to focal ischemia, improved the survival of brain endothelial cells, and reduced FOXO3A nuclear translocation by promoting PI3K/Akt pathway.…”

Section: Discussionsupporting

confidence: 77%

CoQ10 Augments Rosuvastatin Neuroprotective Effect in a Model of Global Ischemia via Inhibition of NF-κB/JNK3/Bax and Activation of Akt/FOXO3A/Bim Cues

2017

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Statins were reported to lower the Coenzyme Q10 (CoQ10) content upon their inhibition of HMG-CoA reductase enzyme and both are known to possess neuroprotective potentials; therefore, the aim is to assess the possible use of CoQ10 as an adds-on therapy to rosuvastatin to improve its effect using global I/R model. Rats were allocated into sham, I/R, rosuvastatin (10 mg/kg), CoQ10 (10 mg/kg) and their combination. Drugs were administered orally for 7 days before I/R. Pretreatment with rosuvastatin and/or CoQ10 inhibited the hippocampal content of malondialdehyde, nitric oxide, and boosted glutathione and superoxide dismutase. They also opposed the upregulation of gp91phox, and p47phox subunits of NADPH oxidase. Meanwhile, both agents reduced content/expression of TNF-α, iNOS, NF-κBp65, ICAM-1, and MPO. Besides, all regimens abated cytochrome c, caspase-3 and Bax, but increased Bcl-2 in favor of cell survival. On the molecular level, they increased p-Akt and its downstream target p-FOXO3A, with the inhibition of the nuclear content of FOXO3A to downregulate the expression of Bim, a pro-apoptotic gene. Additionally, both treatments downregulate the JNK3/c-Jun signaling pathway. The effect of the combination regimen overrides that of either treatment alone. These effects were reflected on the alleviation of the hippocampal damage in CA1 region inflicted by I/R. Together, these findings accentuate the neuroprotective potentials of both treatments against global I/R by virtue of their rigorous multi-pronged actions, including suppression of hippocampal oxidative stress, inflammation, and apoptosis with the involvement of the Akt/FOXO3A/Bim and JNK3/c-Jun/Bax signaling pathways. The study also nominates CoQ10 as an adds-on therapy with statins.

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Section: Discussionsupporting

confidence: 77%

CoQ10 Augments Rosuvastatin Neuroprotective Effect in a Model of Global Ischemia via Inhibition of NF-κB/JNK3/Bax and Activation of Akt/FOXO3A/Bim Cues

2017

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“…To further confirm that increased proliferation of HeLa and IMR90 cells by continuous exposure to an EMF is mainly due to decreased ROS levels, we examined the intracellular ROS-mediated signaling pathways that control cell growth. Several studies have shown that reduced intracellular ROS levels by antioxidants increase phosphorylation of Erk1/2 and Akt [ 28 , 29 ]. Consistent with this, we observed phosphorylation of Akt and Erk1/2 in HeLa and IMR-90 cells exposed to an EMF for 1, 6, 12, and 24 h by western blot analysis.…”

Section: Resultsmentioning

confidence: 99%

A 60 Hz uniform electromagnetic field promotes human cell proliferation by decreasing intracellular reactive oxygen species levels

Song

Yoon

et al. 2018

PLoS ONE

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Previously, we showed that exposure of human normal and cancer cells to a 6 mT, 60 Hz gradient electromagnetic field (EMF) induced genotoxicity. Here, we investigated the cellular effects of a uniform EMF. Single or repetitive exposure to a 6 mT, 60 Hz uniform EMF neither induced DNA damage nor affected cell viability in HeLa and primary IMR-90 fibroblasts. However, continuous exposure of these cells to an EMF promoted cell proliferation. Cell viability increased 24.4% for HeLa and 15.2% for IMR-90 cells after a total 168 h exposure by subculture. This increase in cell proliferation was directly correlated with EMF strength and exposure time. When further incubated without EMF, cell proliferation slowed down to that of unexposed cells, suggesting that the proliferative effect is reversible. The expression of cell cycle markers increased in cells continuously exposed to an EMF as expected, but the distribution of cells in each stage of the cell cycle did not change. Notably, intracellular reactive oxygen species levels decreased and phosphorylation of Akt and Erk1/2 increased in cells exposed to an EMF, suggesting that reduced levels of intracellular reactive oxygen species play a role in increased proliferation. These results demonstrate that EMF uniformity at an extremely low frequency (ELF) is an important factor in the cellular effects of ELF-EMF.

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“…We have previously demonstrated that Akt phosphorylation level is decreased in MnSOD transfected 7721 cells, but is elevated in anti-sense MnSOD transfected ones [19] , [24] . Furthermore, GSH have been reported to activate PI3K/Akt signaling and inhibit the activation of FOXO3 [25] . Our results confirmed that ROS can activate Akt, and demonstrated that ROS-induced telomerase activity may be correlated with Akt activation.…”

Section: Discussionmentioning

confidence: 99%

NAC selectively inhibit cancer telomerase activity: A higher redox homeostasis threshold exists in cancer cells

Wang

et al. 2016

Redox Biology

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Telomerase activity controls telomere length, and this plays an important role in stem cells, aging and tumors. Antioxidant was shown to protect telomerase activity in normal cells but inhibit that in cancer cells, but the underlying mechanism is elusive. Here we found that 7721 hepatoma cells held a higher redox homeostasis threshold than L02 normal liver cells which caused 7721 cells to have a higher demand for ROS; MnSOD over-expression in 7721 decreased endogenous reactive oxygen species (ROS) and inhibited telomerase activity; Akt phosphorylation inhibitor and NAC both inhibited 7721 telomerase activity. The over-elimination of ROS by NAC resulted in the inhibition of Akt pathway. Our results suggest that ROS is involved in the regulation of cancer telomerase activity through Akt pathway. The different intracellular redox homeostasis and antioxidant system in normal cells and tumor cells may be the cause of the opposite effect on telomerase activity in response to NAC treatment. Our results provide a theoretical base of using antioxidants selectively inhibit cancer telomerase activity. Findings of the present study may provide insights into novel approaches for cancer treatment.

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Glutathione Suppresses Cerebral Infarct Volume and Cell Death after Ischemic Injury: Involvement of FOXO3 Inactivation and Bcl2 Expression

Cited by 53 publications

References 75 publications

CoQ10 Augments Rosuvastatin Neuroprotective Effect in a Model of Global Ischemia via Inhibition of NF-κB/JNK3/Bax and Activation of Akt/FOXO3A/Bim Cues

CoQ10 Augments Rosuvastatin Neuroprotective Effect in a Model of Global Ischemia via Inhibition of NF-κB/JNK3/Bax and Activation of Akt/FOXO3A/Bim Cues

A 60 Hz uniform electromagnetic field promotes human cell proliferation by decreasing intracellular reactive oxygen species levels

NAC selectively inhibit cancer telomerase activity: A higher redox homeostasis threshold exists in cancer cells

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