scholarly journals Anti-Apoptotic and Antioxidant Effects of 3-Epi-Iso-Seco-Tanapartholide Isolated from Artemisia argyi against Iodixanol-Induced Kidney Epithelial Cell Death

Biomolecules ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 867
Author(s):  
Dahae Lee ◽  
Kem Ok Kim ◽  
Dongho Lee ◽  
Ki Sung Kang
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Epithelial Cell ◽  
Contrast Agent ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Nrf2 Pathway ◽  
Artemisia Argyi ◽  
Kidney Epithelial Cell ◽  
Epithelial Cell Death

Iodixanol is a non-ionic iso-osmolar contrast agent, but it is a risk factor for kidney damage and increases morbidity and mortality. In this study, we investigated the effect of 9 sesquiterpenes isolated from mugwort (Artemisia argyi) in contrast agent-induced cytotoxicity in LLC-PK1 cells. Cells were exposed to nine sesquiterpene compounds for 2 h, followed by incubation with iodixanol for 3 h. Cell viability was assessed using the Ez-Cytox assay. The level of reactive oxygen species was measured using 2′,7′-dichlorodihydrofluorescein diacetate staining. Apoptotic cell death was detected using annexin V/PI staining. In addition, immunofluorescence staining and western blotting were performed using antibodies against proteins related to apoptosis, oxidative stress, and MAPK pathways. The most effective 3-epi-iso-seco-tanapartholide (compound 8) among the 9 sesquiterpene compounds protected LLC-PK1 cells from iodixanol-induced cytotoxicity, oxidative stress, and apoptotic cell death. Pretreatment with compound 8 reversed iodixanol-induced increases in the expression of JNK, ERK, p38, Bax, caspase-3, and caspase-9. It also reversed the iodixanol-induced decrease in Bcl-2 expression. Furthermore, pretreatment with compound 8 caused nuclear translocation of Nrf2 and upregulated HO-1 via the Nrf2 pathway in iodixanol-treated LLC-PK1 cells. Thus, we demonstrated here that compound 8 isolated from A. argyi has the potential to effectively prevent iodixanol-induced kidney epithelial cell death via the caspase-3/MAPK pathways and HO-1 via the Nrf2 pathway.

scholarly journals Antioxidant and Anti-Inflammatory Effects of 3-Dehydroxyceanothetric Acid 2-Methyl Ester Isolated from Ziziphus jujuba Mill. against Cisplatin-Induced Kidney Epithelial Cell Death

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1614
Author(s):  
Dahae Lee ◽  
Kyo Bin Kang ◽  
Gwi Seo Hwang ◽  
You-Kyoung Choi ◽  
Tae Kon Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Methyl Ester ◽  
Epithelial Cell ◽  
Heme Oxygenase 1 ◽  
Nuclear Factor ◽  
Kidney Epithelial Cell ◽  
Ziziphus Jujuba ◽  
Anti Inflammatory ◽  
Epithelial Cell Death

Cisplatin is a platinum-based chemotherapeutic agent for treating solid tumors; however, it presents a risk factor for nephropathy. In the present study, we investigated the antioxidant and anti-inflammatory effects of 3-dehydroxyceanothetric acid 2-methyl ester (3DC2ME) isolated from Ziziphus jujuba Mill. in LLC-PK1 cells following cisplatin-induced cytotoxicity. These cells were exposed to 3DC2ME for 2 h, followed by treatment with cisplatin for 24 h. The treated cells were subjected to cell viability analysis using the Ez-Cytox assay. Reactive oxygen species (ROS) were detected via 2′, 7′- dichlorodihydrofluorescein diacetate (DCFH-DA) staining. In addition, western blotting and fluorescent immunostaining were performed to evaluate protein expressions related to oxidative stress and inflammation pathways. Pretreatment with 3DC2ME protected LLC-PK1 cells from cisplatin-induced cytotoxicity and oxidative stress. In addition, pretreatment with 3DC2ME upregulated heme oxygenase 1 (HO-1) via the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in the cisplatin-treated LLC-PK1 cells. Furthermore, the increase in the expressions of IκB kinase α/β (IKKα/β), inhibitor of kappa B alpha (IκBα), nuclear factor kappa B (NF-κB), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in these cells was inhibited. These results provide basic scientific evidence for understanding the antioxidant and anti-inflammatory effects of 3DC2ME isolated from Z. jujuba against cisplatin-induced kidney epithelial cell death.

4-hydroxynonenal induces a cellular redox status-related activation of the caspase cascade for apoptotic cell death

2000 ◽  
Vol 113 (4) ◽  
pp. 635-641 ◽  
Author(s):  
W. Liu ◽  
M. Kato ◽  
A.A. Akhand ◽  
A. Hayakawa ◽  
H. Suzuki ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Dna Fragmentation ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
K562 Cells ◽  
Apoptotic Cell Death ◽  
Jurkat Cells ◽  
Substrate Peptide ◽  
Caspase Cascade

4-Hydroxynonenal (HNE), a diffusible product of lipid peroxidation, has been suggested to be a key mediator of oxidative stress-induced cell death. In this study, we partially characterized the mechanism of HNE-mediated cytotoxicity. Incubation of human T lymphoma Jurkat cells with 20–50 μM HNE led to cell death accompanied by DNA fragmentation. Western blot analysis showed that HNE-treatment induced time- and dose-dependent activation of caspase-8, caspase-9 and caspase-3. HNE-induced caspase-3 processing was confirmed by a flow cytometric demonstration of increased catalytic activity on the substrate peptide. HNE treatment also led to remarkable cleavage of poly(ADP-ribose) polymerase (PARP), which was prevented by pretreatment of cells with DEVD-FMK as a caspase-3 inhibitor. The HNE-mediated activation of caspases, cleavage of PARP and DNA fragmentation were blocked by antioxidants cysteine, N-acety-L-cysteine and dithiothreitol, but not by two other HNE-reactive amino acids lysine and histidine, or by cystine, the oxidized form of cysteine. HNE rapidly decreased levels of intracellular reduced glutathione (GSH) and its oxidized form GSSG, and these were also attenuated by the reductants. Coincubation of Jurkat cells with a blocking anti-Fas antibody prevented Fas-induced but not HNE-induced activation of caspase-3. HNE also activated caspase-3 in K562 cells that do not express functional Fas. Our results thereby demonstrate that HNE triggers oxidative stress-linked apoptotic cell death through activation of the caspase cascade. The results also suggest a possible mechanism involving a direct scavenge of intracellular GSH by HNE.

Progressive apoptotic cell death triggered by transient oxidative insult in H9c2 rat ventricular cells: a novel pattern of apoptosis and the mechanisms

2004 ◽  
Vol 286 (6) ◽  
pp. H2169-H2182 ◽  
Author(s):  
Hong Han ◽  
Hong Long ◽  
Huizhen Wang ◽  
Jingxiong Wang ◽  
Yiqiang Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Time Dependent ◽  
Ros Production ◽  
Cytochrome C Release ◽  
Ventricular Cells ◽  
Mitochondrial Death Pathway ◽  
Oxidative Insult

Many pathophysiological processes are associated with oxidative stress and progressive cell death. Oxidative stress is an apoptotic inducer that is known to cause rapid cell death. Here we show that a brief oxidative insult (5-min exposure to 400 μM H2O2), although it did not kill H9c2 rat ventricular cells during the exposure, triggered an intracellular death cascade leading to delayed time-dependent cell death starting from 1 h after the insult had been withdrawn, and this post-H2O2 cell death cumulated gradually, reaching a maximum level 8 h after H2O2 withdrawal. By comparison, sustained exposure to H2O2 caused complete cell death within a narrow time frame (2 h). The time-dependent post-H2O2 cell death was typical of apoptosis, both morphologically (cell shrinkage and nuclear condensation) and biochemically (DNA fragmentation, extracellular exposure of phosphatidylserines, and caspase-3 activation). A dichlorofluorescein fluorescent signal showed a time-dependent endogenous increase of reactive oxygen species (ROS) production, which was almost abolished by inhibition of the mitochondrial electron transport chain. Application of antioxidants (vitamin E or DTT) before H2O2 addition or after H2O2 withdrawal prevented the H2O2-triggered progressive ROS production and apoptosis. Sequential appearance of events associated with activation of the mitochondrial death pathway was found, including progressive dissipation of mitochondrial membrane potential, cytochrome c release, and late activation of caspase-3. In conclusion, transient oxidative stress triggers an intrinsic program leading to self-sustained apoptosis in H9c2 cells via cumulative production of mitochondrial ROS and subsequent activation of the mitochondrial death pathway. This pattern of apoptosis may contribute to the progressive and long-lasting cell loss in some degenerative diseases.

scholarly journals Involvement of Oxidative Stress and Caspase-3 in Cortical Infarction after Photothrombotic Ischemia in Mice

2000 ◽  
Vol 20 (12) ◽  
pp. 1690-1701 ◽  
Author(s):  
Gyung W. Kim ◽  
Taku Sugawara ◽  
Pak H. Chan
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Treated Group ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Ischemic Lesion ◽  
Related Cell

Apoptosis-related cell death is linked to oxidative stress and caspases in experimental cerebral ischemia, However, the role of oxidative stress in caspase activation and subsequent apoptotic cell death after cerebral ischemia is unknown, The authors evaluated the role of oxidative stress in ischemic cerebral infarction after photothrombosis and the relation between oxidative stress and caspase-related cell death 6 and 24 hours after ischemia with and without U-74389G, a potent free radical scavenger (10 mg/kg, 30 minutes before and after ischemia induction). Reactive oxygen species, detected by hydroethidine oxidation, and cytosolic cytochrome c were detected in early ischemic lesions. Western blot analysis showed the cleaved form and the level of the proform of caspase-3 in the ischemic lesion 24 hours after ischemia. Decreased caspase-3 immunoreactivity was detected in the antioxidant-treated group after ischemia. Decreased DNA fragmentation and laddering were detected and the lesion was smaller in the treated group after ischemia compared with the untreated group. Oxidative stress and cytochrome c release occur in the ischemic lesion after photothrombotic ischemia. The free radical scavenger attenuated caspase-3 up-regulation, DNA fragmentation, and the final lesion. The authors concluded that oxidative stress may mediate caspase-related apoptotic cell death and subsequent cortical infarction after photothrombotic ischemia.

scholarly journals SPC212 Human Mesothelioma Cell Underwent Apoptosis, Oxidative Stress, Morhological Deformation Following Astaxanthin Treatment

2021 ◽  
Author(s):  
Sedat Kacar ◽  
Tuğba S. Sevimli ◽  
Varol Sahinturk
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Stress Test ◽  
Annexin V ◽  
Bioactive Compound ◽  
Cancer Types ◽  
Effective Doses ◽  
Annexin V Assay

Abstract Although astaxanthin (ASX) is one type of carotenoid, it is a more bioactive compound than other carotenoids. Despite its utilization against different cancer types, the effect of ASX on mesothelioma has yet to be well-studied. In this study, our goal is to ascertain how ASX will affect SPC212 human mesothelioma cells. First, the effective doses of ASX against SPC212 cells were uncovered by the MTT test. Thereafter, with flow cytometry analysis, Annexin-V and caspase 3/7 assay were implemented for the evaluation of apoptotic cell death and an oxidative stress test was carried out to determine how the free radicals changed. Ultimately, the cells’ morphology was examined under a light microscope. The effective doses of ASX were found as 50,100 and 200 µM. In Annexin V assay, the total apoptosis increased to around 12%, 30%, and %45 with increasing doses of ASX. In the caspase 3/7 assay, the total apoptosis was around %25 and %38 at 100 and 200 µM. In oxidative stress analysis, ROS-positive cells rose from 4.54 at the lowest dose to 86.95 at the highest dose. In morphological analysis, cellular shrinkage, decrease in cell density, swelling and vacuolations in some cells, membrane blebbing and apoptotic bodies are observed in ASX-treated cells. To conclude, the current study provided insights into the efficacy and effects of ASX against SPC212 mesothelioma cells regarding morphology, proliferation and cell death for future studies.

scholarly journals SPC212 Human Mesothelioma Cell Underwent Apoptosis, Oxidative Stress, Morhological Deformation Following Astaxanthin Treatment

2021 ◽  
Author(s):  
Sedat Kacar ◽  
Tuğba S. Sevimli ◽  
Varol Sahinturk
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Stress Test ◽  
Annexin V ◽  
Bioactive Compound ◽  
Cancer Types ◽  
Effective Doses ◽  
Annexin V Assay

Abstract Although astaxanthin (ASX) is one type of caretonoids, it is more bioactive compound than other carotenoids. Despite its utilization against different cancer types, effect of ASX on mesothelioma has yet to be well-studied. In this study, our goal is to ascertain how ASX will affect SPC212 human mesothelioma cells. First, the effective doses of ASX against SPC212 cells was uncovered by MTT test. Thereafter, with flow cytometry analysis, Annexin-V and caspase 3/7 assay was implemented for the evaluation of apoptotic cell death and oxidative stress test was carried out to determine how the free radicals changed. Ultimately, the cells’ morphology was examined under light microscope. The effective doses of ASX were found as 50,100 and 200 µM. In Annexin V assay, the total apoptosis increased to around 12%, 30% and %45 with increasing doses of ASX. In caspase 3/7 assay, the total apoptosis was around %25 and %38 at 100 and 200 µM. In oxidative stress analysis, ROS positive cells rose from 4.54 at the lowest dose to 86.95 at the highest dose. In morphological analysis, cellular shrinkage, decrease in cell density, swelling and vacuolations in some cells, membrane blebbing and apoptotic bodies are observed in ASX-treated cells. To conclude, the current study provided insights into the efficacy and effects of ASX against SPC212 mesothelioma cells regarding morphology, proliferation and cell death for the future studies.

scholarly journals Polyhexamethylene Guanidine Phosphate Induces Apoptosis through Endoplasmic Reticulum Stress in Lung Epithelial Cells

2021 ◽  
Vol 22 (3) ◽  
pp. 1215
Author(s):  
Mi Ho Jeong ◽  
Mi Seon Jeon ◽  
Ga Eun Kim ◽  
Ha Ryong Kim
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Epithelial Cell ◽  
Er Stress ◽  
Lung Fibrosis ◽  
A549 Cells ◽  
Polyhexamethylene Guanidine ◽  
Lung Epithelial ◽  
Epithelial Cell Death ◽  
Guanidine Phosphate

Airway epithelial cell death contributes to the pathogenesis of lung fibrosis. Polyhexamethylene guanidine phosphate (PHMG-p), commonly used as a disinfectant, has been shown to be strongly associated with lung fibrosis in epidemiological and toxicological studies. However, the molecular mechanism underlying PHMG-p-induced epithelial cell death is currently unclear. We synthesized a PHMG-p–fluorescein isothiocyanate (FITC) conjugate and assessed its uptake into lung epithelial A549 cells. To examine intracellular localization, the cells were treated with PHMG-p–FITC; then, the cytoplasmic organelles were counterstained and observed with confocal microscopy. Additionally, the organelle-specific cell death pathway was investigated in cells treated with PHMG-p. PHMG-p–FITC co-localized with the endoplasmic reticulum (ER), and PHMG-p induced ER stress in A549 cells and mice. The ER stress inhibitor tauroursodeoxycholic acid (TUDCA) was used as a pre-treatment to verify the role of ER stress in PHMG-p-induced cytotoxicity. The cells treated with PHMG-p showed apoptosis, which was inhibited by TUDCA. Our results indicate that PHMG-p is rapidly located in the ER and causes ER-stress-mediated apoptosis, which is an initial step in PHMG-p-induced lung fibrosis.

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