Hydrogen peroxide and hydroxyl radical involvement in the activation of caspase-3 in chemically induced apoptosis of HL-60 cells

Reactive oxygen species, including hydrogen peroxide (H2O2), are generated during ischemia-reperfusion and are critically involved in acute renal failure. The present studies examined the role of the extracellular signal-regulated kinase (ERK) pathway in H2O2-induced renal proximal tubular cells (RPTC) apoptosis. Exposure of RPTC to 1 mM H2O2resulted in apoptosis and activation of ERK1/2 and Akt. Pretreatment with the specific MEK inhibitors, U0126 and PD98059, or adenoviral infection with a construct that encodes a negative mutant of MEK1, protected cells against H2O2-induced apoptosis. In contrast, expression of constitutively active MEK1 enhanced H2O2-induced apoptosis. H2O2induced activation of caspase-3 and phosphorylation of histone H2B at serine 14, a posttranslational modification required for nuclear condensation, which also were blocked by ERK1/2 inhibition. Furthermore, blockade of ERK1/2 resulted in an increase in Akt phosphorylation and blockade of Akt potentiated apoptosis and diminished the protective effect conferred by ERK inhibition in H2O2-treated cells. Although Z-DEVD-FMK, a caspase-3 inhibitor, was able to inhibit histone H2B phosphorylation and apoptosis, it did not affect ERK1/2 phosphorylation. We suggest that ERK elicits apoptosis in epithelial cells by activating caspase-3 and inhibiting Akt pathways and elicits nuclear condensation through caspase-3 and histone H2B phosophorylation during oxidant injury.

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Neuroprotective effects of N-acetylglucosamine against hydrogen peroxide-induced apoptosis in human neuronal SK-N-SH cells by inhibiting the activation of caspase-3, PARP, and p38

Food Science and Biotechnology ◽

10.1007/s10068-013-0155-0 ◽

2013 ◽

Vol 22 (3) ◽

pp. 853-858 ◽

Cited By ~ 6

Author(s):

Ha Na Choi ◽

Mi Ja Chung ◽

Jae Kweon Park ◽

Yong Il Park

Keyword(s):

Hydrogen Peroxide ◽

Caspase 3 ◽

Neuroprotective Effects ◽

Induced Apoptosis

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The roles of caspase-3 and bcl-2 in chemically-induced apoptosis but not necrosis of renal epithelial cells

Oncogene ◽

10.1038/sj.onc.1203060 ◽

1999 ◽

Vol 18 (47) ◽

pp. 6505-6512 ◽

Cited By ~ 57

Author(s):

Yi Zhan ◽

Bob van de Water ◽

Yuping Wang ◽

James L Stevens

Keyword(s):

Epithelial Cells ◽

Caspase 3 ◽

Renal Epithelial Cells ◽

Chemically Induced ◽

Induced Apoptosis

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Time Dependent Appearance of Selected Apoptotic Markers and Usefulness of Their Detection In vitro

Acta Medica (Hradec Kralove Czech Republic) ◽

10.14712/18059694.2019.70 ◽

2002 ◽

Vol 45 (4) ◽

pp. 135-144 ◽

Cited By ~ 1

Author(s):

Emil Rudolf ◽

Miroslav Červinka

Keyword(s):

Caspase 3 ◽

Potassium Chromate ◽

Experimental Setting ◽

Apoptotic Pathway ◽

Detection Systems ◽

Chemically Induced ◽

Cell Blebbing ◽

Temporary Decrease ◽

Induced Apoptosis

Many experiments have demonstrated that some cell lines are resistant to chemically induced apoptosis in vitro, and that apoptosis itself is far from being a homogenous phenomenon. Here we show that 10 μg/ml etoposide elicited only minor changes in Bowes human melanoma cells (temporary decrease in cell viability and proliferation, transient phospatidylserine externalization and caspase-3 activation), which weren’t clearly capable to start apoptotic pathway in the entire treated population. On the other hand, potassium chromate at concentration of 150 μg/ml executed cell death bearing some features of apoptosis (cell blebbing, caspase-3 activation and cytoskeletal changes) but lacking or showing weakly others (DNA fragmentation and phospatidylserine externalization). Our results suggest that in detecting apoptosis several faultproof detection systems are to be used to avoid misleading results and conclusions in each experimental setting.

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Hydrogen peroxide-induced apoptosis in HL-60 cells requires caspase-3 activation

Free Radical Research ◽

10.1080/10715769900300081 ◽

1999 ◽

Vol 30 (1) ◽

pp. 73-83 ◽

Cited By ~ 112

Author(s):

Tatsuya Matsura ◽

Masachika Kai ◽

Yasuyoshi Fujii ◽

Hisao Ito ◽

Kazuo Yamada

Keyword(s):

Hydrogen Peroxide ◽

Caspase 3 ◽

Induced Apoptosis

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Taraxerol protects the human hepatic L02 cells from hydrogen peroxide-induced apoptosis

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v12i2.30985 ◽

2017 ◽

Vol 12 (2) ◽

pp. 20 ◽

Cited By ~ 1

Author(s):

Xiang-Yang Yao ◽

Qin Bai

Keyword(s):

Oxidative Stress ◽

Hydrogen Peroxide ◽

Caspase 3 ◽

Protective Agent ◽

Cytoprotective Effect ◽

Lactate Dehydrogenase Release ◽

Anti Cancer ◽

Induced Apoptosis ◽

L02 Cells ◽

Cancer Activity

Taraxerol is known to exhibit anti-inflammatory and anti-cancer activity. However, cytoprotective effect of taraxerol on hepatocytes has not been reported. In the present study, we investigated the hepatoprotective effect of taraxerol in the human hepatic L02 cells injured by hydrogen peroxide (H2O2). Taraxerol decreased H2O2-induced cell viability loss and lactate dehydrogenase release. Taraxerol also inhibited H2O2-induced cell apoptosis. Further, taraxerol attenuated H2O2-induced increase in cleaved-caspase-3 and cleaved-PARP. H2O2-activated p38 and JNK were also inhibited by taraxerol. These data suggest that taraxerol could protect the L02 cells against H2O2-induced apoptosis via suppression of p38 and JNK. Taraxerol may be an effective protective agent against oxidative stress-induced liver injury.

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miR-21 Reduces Hydrogen Peroxide-Induced Apoptosis in c-kit+Cardiac Stem Cells In Vitro through PTEN/PI3K/Akt Signaling

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/5389181 ◽

2016 ◽

Vol 2016 ◽

pp. 1-14 ◽

Cited By ~ 15

Author(s):

Wenwen Deng ◽

Yan Wang ◽

Xianping Long ◽

Ranzun Zhao ◽

Zhenglong Wang ◽

...

Keyword(s):

Hydrogen Peroxide ◽

Stem Cells ◽

Caspase 3 ◽

Mrna Level ◽

Cell Types ◽

Akt Signaling ◽

Selective Inhibitor ◽

Cardiac Stem Cells ◽

Induced Apoptosis

The low survival rate of cardiac stem cells (CSCs) in the infarcted myocardium hampers cell therapy for ischemic cardiomyopathy. MicroRNA-21 (miR-21) and one of its target proteins, PTEN, contribute to the survival and proliferation of many cell types, but their prosurvival effects in c-kit+CSC remain unclear. Thus, we hypothesized that miR-21 reduces hydrogen peroxide- (H2O2-) induced apoptosis in c-kit+CSC and estimated the contribution of PTEN/PI3K/Akt signaling to this oxidative circumstance. miR-21 mimics efficiently reduced H2O2-induced apoptosis in c-kit+CSC, as evidenced by the downregulation of the proapoptosis proteins caspase-3 and Bax and upregulation of the antiapoptotic Bcl-2. In addition, the gain of function of miR-21 in c-kit+CSC downregulated the protein level of PTEN although its mRNA level changed slightly; in the meantime, miR-21 overexpression also increased phospho-Akt (p-Akt). The antiapoptotic effects of miR-21 were comparable with Phen (bpV), the selective inhibitor of PTEN, while miR-21 inhibitor or PI3K’s inhibitor LY294002 efficiently attenuated the antiapoptotic effect of miR-21. Taken together, these results indicate that the anti-H2O2-induced apoptosis effect of miR-21 in c-kit+CSC is contributed by PTEN/PI3K/Akt signaling. miR-21 could be a potential molecule to facilitate the c-kit+CSC therapy in ischemic myocardium.

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Hexarelin Modulation of MAPK and PI3K/Akt Pathways in Neuro-2A Cells Inhibits Hydrogen Peroxide—Induced Apoptotic Toxicity

Pharmaceuticals ◽

10.3390/ph14050444 ◽

2021 ◽

Vol 14 (5) ◽

pp. 444

Author(s):

Ramona Meanti ◽

Laura Rizzi ◽

Elena Bresciani ◽

Laura Molteni ◽

Vittorio Locatelli ◽

...

Keyword(s):

Hydrogen Peroxide ◽

Cell Viability ◽

Caspase 3 ◽

Mrna Levels ◽

Protective Effects ◽

Neuroprotective Effects ◽

Caspase 7 ◽

Induced Apoptosis

Hexarelin, a synthetic hexapeptide, exerts cyto-protective effects at the mitochondrial level in cardiac and skeletal muscles, both in vitro and in vivo, may also have important neuroprotective bioactivities. This study examined the inhibitory effects of hexarelin on hydrogen peroxide (H2O2)-induced apoptosis in Neuro-2A cells. Neuro-2A cells were treated for 24 h with various concentrations of H2O2 or with the combination of H2O2 and hexarelin following which cell viability and nitrite (NO2−) release were measured. Cell morphology was also documented throughout and changes arising were quantified using Image J skeleton and fractal analysis procedures. Apoptotic responses were evaluated by Real-Time PCR (caspase-3, caspase-7, Bax, and Bcl-2 mRNA levels) and Western Blot (cleaved caspase-3, cleaved caspase-7, MAPK, and Akt). Our results indicate that hexarelin effectively antagonized H2O2-induced damage to Neuro-2A cells thereby (i) improving cell viability, (ii) reducing NO2− release and (iii) restoring normal morphologies. Hexarelin treatment also reduced mRNA levels of caspase-3 and its activation, and modulated mRNA levels of the BCL-2 family. Moreover, hexarelin inhibited MAPKs phosphorylation and increased p-Akt protein expression. In conclusion, our results demonstrate neuroprotective and anti-apoptotic effects of hexarelin, suggesting that new analogues could be developed for their neuroprotective effects.

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