scholarly journals Identification of Renoprotective Phytosterols from Mulberry (Morus alba) Fruit against Cisplatin-Induced Cytotoxicity in LLC-PK1 Kidney Cells

Plants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2481
Author(s):  
Dahae Lee ◽  
Seoung Rak Lee ◽  
Bang Ju Park ◽  
Ji Hoon Song ◽  
Jung Kyu Kim ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Cell Damage ◽  
Folk Medicine ◽  
Morus Alba ◽  
Mass Spectrometry Data ◽  
Protective Effects ◽  
Isolation And Identification ◽  
Control Value ◽  
Induced Apoptosis ◽  
Mulberry Tree

The aim of this study was to explore the protective effects of bioactive compounds from the fruit of the mulberry tree (Morus alba L.) against cisplatin-induced apoptosis in LLC-PK1 pig kidney epithelial cells. Morus alba fruit is a well-known edible fruit commonly used in traditional folk medicine. Chemical investigation of M. alba fruit resulted in the isolation and identification of six phytosterols (1–6). Their structures were determined as 7-ketositosterol (1), stigmast-4-en-3β-ol-6-one (2), (3β,6α)-stigmast-4-ene-3,6-diol (3), stigmast-4-ene-3β,6β-diol (4), 7β-hydroxysitosterol 3-O-β-d-glucoside (5), and 7α-hydroxysitosterol 3-O-β-d-glucoside (6) by analyzing their physical and spectroscopic data as well as liquid chromatography/mass spectrometry data. All compounds displayed protective effects against cisplatin-induced LLC-PK1 cell damage, improving cisplatin-induced cytotoxicity to more than 80% of the control value. Compound 1 displayed the best effect at a relatively low concentration by inhibiting the percentage of apoptotic cells following cisplatin treatment. Its molecular mechanisms were identified using Western blot assays. Treatment of LLC-PK1 cells with compound 1 decreased the upregulated phosphorylation of p38 and c-Jun N-terminal kinase (JNK) following cisplatin treatment. In addition, compound 1 significantly suppressed cleaved caspase-3 in cisplatin-induced LLC-PK1 cells. Taken together, these findings indicated that cisplatin-induced apoptosis was significantly inhibited by compound 1 in LLC-PK1 cells, thereby supporting the potential of 7-ketositosterol (1) as an adjuvant candidate for treating cisplatin-induced nephrotoxicity.

scholarly journals Isorhynchophylline Protects PC12 Cells Against Beta-Amyloid-Induced Apoptosis via PI3K/Akt Signaling Pathway

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Yan-Fang Xian ◽  
Zhi-Xiu Lin ◽  
Qing-Qiu Mao ◽  
Jian-Nan Chen ◽  
Zi-Ren Su ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Pc12 Cells ◽  
Molecular Mechanisms ◽  
Glycogen Synthase ◽  
Neuroprotective Effect ◽  
Protective Action ◽  
Protective Effects ◽  
Phosphorylated Akt ◽  
Induced Apoptosis

The neurotoxicity of amyloid-β(Aβ) has been implicated as a critical cause of Alzheimer’s disease. Isorhynchophylline (IRN), an oxindole alkaloid isolated fromUncaria rhynchophylla,exerts neuroprotective effect againstAβ25–35-induced neurotoxicityin vitro. However, the exact mechanism for its neuroprotective effect is not well understood. The present study aimed to investigate the molecular mechanisms underlying the protective action of IRN againstAβ25–35-induced neurotoxicity in cultured rat pheochromocytoma (PC12) cells. Pretreatment with IRN significantly increased the cell viability, inhibited the release of lactate dehydrogenase and the extent of DNA fragmentation inAβ25–35-treated cells. IRN treatment was able to enhance the protein levels of phosphorylated Akt (p-Akt) and glycogen synthase kinase-3β(p-GSK-3β). Lithium chloride blockedAβ25–35-induced cellular apoptosis in a similar manner as IRN, suggesting that GSK-3βinhibition was involved in neuroprotective action of IRN. Pretreatment with LY294002 completely abolished the protective effects of IRN. Furthermore, IRN reversedAβ25–35-induced attenuation in the level of phosphorylated cyclic AMP response element binding protein (p-CREB) and the effect of IRN could be blocked by the PI3K inhibitor. These experimental findings unambiguously suggested that the protective effect of IRN againstAβ25–35-induced apoptosis in PC12 cells was associated with the enhancement of p-CREB expression via PI3K/Akt/GSK-3βsignaling pathway.

scholarly journals Emodin Alleviates Hydrogen Peroxide-Induced Inflammation and Oxidative Stress via Mitochondrial Dysfunction by Inhibiting the PI3K/mTOR/GSK3β Pathway in Neuroblastoma SH-SY5Y Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Rui Li ◽  
Wenzhou Liu ◽  
Li Ou ◽  
Feng Gao ◽  
Min Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Cell Damage ◽  
Neuroblastoma Cells ◽  
Inflammatory Factors ◽  
Protective Mechanism ◽  
Human Neuroblastoma ◽  
Induced Apoptosis

Emodin is an active monomer extracted from rhubarb root, which has many biological functions, including anti-inflammation, antioxidation, anticancer, and neuroprotection. However, the protective effect of emodin on nerve injury needs to be further elucidated. The purpose of this study is to investigate the effect of emodin on the neuroprotection and the special molecular mechanism. Here, the protective activity of emodin inhibiting H2O2-induced apoptosis and neuroinflammation as well as its molecular mechanisms was examined using human neuroblastoma cells (SH-SY5Y cells). The results showed that emodin significantly enhanced cell viability, reduced cell apoptosis and LDH release. Simultaneously, emodin downregulated H2O2-induced inflammatory factors, including IL-6, NO, and TNF-α, and alleviated H2O2-induced oxidative stress and mitochondrial dysfunction in SH-SY5Y cells. In addition, emodin inhibited the activation of the PI3K/mTOR/GSK3β signaling pathway. What is more, the PI3K/mTOR/GSK3β pathway participated in the protective mechanism of emodin on H2O2-induced cell damage. Collectively, it suggests that emodin alleviates H2O2-induced apoptosis and neuroinflammation potentially by regulating the PI3K/mTOR/GSK3β signaling pathway.

scholarly journals Oregano Essential Oil Induces SOD1 and GSH Expression through Nrf2 Activation and Alleviates Hydrogen Peroxide-Induced Oxidative Damage in IPEC-J2 Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Yi Zou ◽  
Jun Wang ◽  
Jian Peng ◽  
Hongkui Wei
Keyword(s):  
Hydrogen Peroxide ◽  
Essential Oil ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Cell Damage ◽  
Antioxidant Response ◽  
Related Factor ◽  
Protective Effects ◽  
Oregano Essential Oil ◽  
Protein Levels

Oregano essential oil (OEO) has long been used to improve the health of animals, particularly their intestinal health. The health benefits of OEO are generally attributed to antioxidative actions, but the mechanisms remain unclear. Here, we investigate the antioxidative effects of OEO and their underlying molecular mechanisms in porcine small intestinal epithelial (IPEC-J2) cells. We found that OEO treatment prior to hydrogen peroxide (H2O2) exposure increased cell viability and prevented lactate dehydrogenase (LDH) release into the medium. H2O2-induced reactive oxygen species (ROS) and malondialdehyde (MDA) were remarkably suppressed by OEO. OEO dose-dependently increased mRNA and protein levels of the nuclear factor-erythroid 2-related factor-2 (Nrf2) target genes Cu/Zn-superoxide dismutase (SOD1) and g-glutamylcysteine ligase (GCLC, GLCM), as well as intracellular concentrations of SOD1 and glutathione. OEO also increased intranuclear expression of Nrf2 and the activity of an antioxidant response element reporter plasmid in IPEC-J2 cells. The OEO-induced expression of Nrf2-regulated genes and increased SOD1 and glutathione concentrations in IPEC-J2 cells were reduced by Nrf2 small interfering (si) RNAs, counteracting the protective effects of OEO against oxidative stress in IPEC-J2 cells. Our results suggest that OEO protects against H2O2-induced IPEC-J2 cell damage by inducing Nrf2 and related antioxidant enzymes.

scholarly journals Sheng Mai San protects H9C2 cells against hyperglycemia-induced apoptosis

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Bing Pang ◽  
Li-Wei Shi ◽  
Li-juan Du ◽  
Yun-Chu Li ◽  
Mei-Zhen Zhang ◽  
...  
Keyword(s):  
Cell Viability ◽  
Molecular Mechanisms ◽  
Annexin V ◽  
Signalling Pathway ◽  
H9c2 Cell ◽  
Protective Effects ◽  
H9c2 Cells ◽  
P53 Expression ◽  
Fasl Gene ◽  
Induced Apoptosis

Abstract Background Sheng Mai San (SMS) has been proven to exhibit cardio-protective effects. This study aimed to explore the molecular mechanisms of SMS on hyperglycaemia (HG)-induced apoptosis in H9C2 cells. Methods HG-induced H9C2 cells were established as the experimental model, and then treated with SMS at 25, 50, and 100 μg/mL. H9C2 cell viability and apoptosis were quantified using MTT and Annexin V-FITC assays, respectively. Furthermore, Bcl-2/Bax signalling pathway protein expression and Fas and FasL gene expression levels were quantified using western blotting and RT-PCR, respectively. Results SMS treatments at 25, 50, 100 μg/mL significantly improved H9C2 cell viability and inhibited H9C2 cell apoptosis (p < 0.05). Compared to the HG group, SMS treatment at 25, 50, and 100 μg/mL significantly downregulated p53 and Bax expression and upregulated Bcl-2 expression (p < 0.05). Moreover, SMS treatment at 100 μg/mL significantly downregulated Fas and FasL expression level (p < 0.05) when compared to the HG group. Conclusion SMS protects H9C2 cells from HG-induced apoptosis probably by downregulating p53 expression and upregulating the Bcl-2/Bax ratio. It may also be associated with the inhibition of the Fas/FasL signalling pathway.

Tanshinone IIA Suppresses Hypoxia-induced Apoptosis in Medial Vestibular Nucleus Cells Via a Skp2/BKCa Axis

2020 ◽  
Vol 26 (33) ◽  
pp. 4185-4194
Author(s):  
Jing-Jing Zhu ◽  
Shu-Hui Wu ◽  
Xiang Chen ◽  
Ting-Ting Jiang ◽  
Xin-Qian Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Viability ◽  
Cell Apoptosis ◽  
Cell Damage ◽  
Vestibular Nucleus ◽  
Tanshinone Iia ◽  
Medial Vestibular Nucleus ◽  
Protective Effects ◽  
Induced Apoptosis

Background: The aim of the present study was to investigate the protective effects of Tanshinone IIA (Tan IIA) on hypoxia-induced injury in the medial vestibular nucleus (MVN) cells. Methods: An in vitro hypoxia model was established using MVN cells exposed to hypoxia. The hypoxia-induced cell damage was confirmed by assessing cell viability, apoptosis and expression of apoptosis-associated proteins. Oxidative stress and related indicators were also measured following hypoxia modeling and Tan IIA treatment, and the genes potentially involved in the response were predicted using multiple GEO datasets. Results: The results of the present study showed that Tan IIA significantly increased cell viability, decreased cell apoptosis and decreased the ratio of Bax/Bcl-2 in hypoxia treated cells. In addition, hypoxia treatment increased oxidative stress in MVN cells, and treatment with Tan IIA reduced the oxidative stress. The expression of SPhase Kinase Associated Protein 2 (SKP2) was upregulated in hypoxia treated cells, and Tan IIA treatment reduced the expression of SKP2. Mechanistically, SKP2 interacted with large-conductance Ca2+-activated K+ channels (BKCa), regulating its expression, and BKCa knockdown alleviated the protective effects of Tan IIA on hypoxia induced cell apoptosis. Conclusion: The results of the present study suggested that Tan IIA had a protective effect on hypoxia-induced cell damage through its anti-apoptotic and anti-oxidative activity via an SKP2/BKCa axis. These findings suggest that Tan IIA may be a potential therapeutic for the treatment of hypoxia-induced vertigo.

scholarly journals Exopolysaccharides from Bifidobacterium animalis Ameliorate Escherichia coli-Induced IPEC-J2 Cell Damage via Inhibiting Apoptosis and Restoring Autophagy

2021 ◽  
Vol 9 (11) ◽  
pp. 2363
Author(s):  
Lanxin Yuan ◽  
Bingxin Chu ◽  
Shiyan Chen ◽  
Yanan Li ◽  
Ning Liu ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Cell Damage ◽  
Epithelial Cell Line ◽  
Protective Effects ◽  
Protein Levels ◽  
Bifidobacterium Animalis ◽  
Secretory Products ◽  
Induced Apoptosis ◽  
Related Proteins ◽  
Lysosomal Acidification

Enteropathogenic Escherichia coli (EPEC) is a common zoonotic pathogen that causes acute infectious diarrhea. Probiotics like Bifidobacterium are known to help prevent pathogen infections. The protective effects of Bifidobacterium are closely associated with its secretory products exopolysaccharides (EPS). We explored the effects of the EPS from Bifidobacterium animalis subsp. lactis (B. lactis) on ameliorating the damage of an intestinal porcine epithelial cell line (IPEC-J2) during EPEC infection. Pretreatment with EPS alleviated EPEC-induced apoptosis through the restoration of cell morphology and the downregulation of protein expressions of cleaved-caspase 8, cleaved-caspase 3, and cleaved-PARP. EPS-mediated remission of apoptosis significantly improved cell viability during EPEC infection. EPEC infection also resulted in impaired autophagy, as demonstrated by decreased expressions of autophagy-related proteins Beclin 1, ATG5, and microtubule-binding protein light chain-3B (LC3B) and the increased expression of p62 through western blot analysis. However, EPS reversed these effects which indicated that EPS promoted autophagosome formation. Furthermore, EPS prevented the lysosome damage induced by EPEC as it enhanced lysosomal acidification and raised lysosome-associated protein levels, thus promoted autophagosome degradation. Our findings suggest that the amelioration of EPEC-induced cell damages by EPS is associated with the limitation of detrimental apoptosis and the promotion of autophagy flux.

scholarly journals Bacillus amyloliquefaciens SC06 Induced AKT–FOXO Signaling Pathway-Mediated Autophagy to Alleviate Oxidative Stress in IPEC-J2 Cells

Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1545
Author(s):  
Li Tang ◽  
Zihan Zeng ◽  
Yuanhao Zhou ◽  
Baikui Wang ◽  
Peng Zou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Bacillus Amyloliquefaciens ◽  
Transcriptional Activity ◽  
Molecular Mechanisms ◽  
Cell Damage ◽  
Optimal Dose ◽  
Theoretical Support ◽  
Induced Apoptosis ◽  
Foxo Signaling Pathway

Autophagy is a conserved proteolytic mechanism, which degrades and recycles damaged organs and proteins in cells to resist external stress. Probiotics could induce autophagy; however, its underlying molecular mechanisms remain elusive. Our previous study has found that BaSC06 could alleviate oxidative stress by inducing autophagy in rats. This research aimed to verify whether Bacillus amyloliquefaciens SC06 can induce autophagy to alleviate oxidative stress in IPEC-J2 cells, as well as explore its mechanisms. IPEC-J2 cells were first pretreated with 108 CFU/mL BaSC06, and then were induced to oxidative stress by the optimal dose of diquat. The results showed that BaSC06 significantly triggered autophagy, indicated by the up-regulation of LC3 and Beclin1 along with downregulation of p62 in IPEC-J2 cells. Further analysis revealed that BaSC06 inhibited the AKT–FOXO signaling pathway by inhibiting the expression of p-AKT and p-FOXO and inducing the expression of SIRT1, resulting in increasing the transcriptional activity of FOXO3 and gene expression of the ATG5–ATG12 complex to induce autophagy, which alleviated oxidative stress and apoptosis. Taken together, BaSC06 can induce AKT–FOXO-mediated autophagy to alleviate oxidative stress-induced apoptosis and cell damage, thus providing novel theoretical support for probiotics in the prevention and treatment of oxidative damage.

scholarly journals Cudratricusxanthone O Inhibits H2O2-Induced Cell Damage by Activating Nrf2/HO-1 Pathway in Human Chondrocytes

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 788 ◽  
Author(s):  
Eun-Nam Kim ◽  
Hyun-Su Lee ◽  
Gil-Saeng Jeong
Keyword(s):  
Cell Damage ◽  
Protoporphyrin Ix ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Protective Effects ◽  
Inhibitory Effects ◽  
Ros Accumulation ◽  
Tin Protoporphyrin ◽  
Induced Apoptosis ◽  
Radical Damage

Osteoarthritis (OA) is a common joint degenerative disease induced by oxidative stress in chondrocytes. Although induced-heme oxygenase-1 (HO-1) has been found to protect cells against oxygen radical damage, little information is available regarding the use of bioactive compounds from natural sources for regulating the HO-1 pathway to treat OA. In this study, we explored the inhibitory effects of cudratricusxanthone O (CTO) isolated from the Maclura tricuspidata Bureau (Moraceae) on H2O2-induced damage of SW1353 chondrocytes via regulation of the HO-1 pathway. CTO promoted HO-1 expression by enhancing the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) into the nucleus without inducing toxicity. Pretreatment with CTO-regulated reactive oxygen species (ROS) production by inducing expression of antioxidant enzymes in H2O2-treated cells and maintained the functions of H2O2-damaged chondrocytes. Furthermore, CTO prevented H2O2-induced apoptosis by regulating the expression of anti-apoptotic proteins. Treatment with the HO-1 inhibitor tin-protoporphyrin IX revealed that these protective effects were exerted due to an increase in HO-1 expression induced by CTO. In conclusion, CTO protects chondrocytes from H2O2-induced damages—including ROS accumulation, dysfunction, and apoptosis through activation of the Nrf2/HO-1 signaling pathway in chondrocytes and, therefore, is a potential therapeutic agent for OA treatment.

Inhibition of miR-182-5p protects cardiomyocytes from hypoxia-induced apoptosis by targeting CIAPIN1

2018 ◽  
Vol 96 (5) ◽  
pp. 646-654 ◽  
Author(s):  
Yunsong Zhang ◽  
Jun Fang ◽  
Huiwen Ma
Keyword(s):  
Molecular Mechanisms ◽  
Annexin V ◽  
Bioinformatic Analysis ◽  
Luciferase Reporter ◽  
Protective Effects ◽  
Small Interfering Rnas ◽  
Protein Levels ◽  
Hypoxic Conditions ◽  
Induced Apoptosis ◽  
Apoptosis Inhibitor

Myocardial infarction (MI), a type of ischemic heart disease, is generally accompanied by apoptosis of cardiomyocytes. MicroRNAs play the vital roles in the development and physiology of MI. Here, we established a downregulation model of miR-182-5p in H9c2 cells under hypoxic conditions to investigate the potential molecular mechanisms for miR-182-5p in hypoxia-induced cardiomyocyte apoptosis (HICA). RT-qPCR indicated that miR-182-5p levels exhibit a time-dependent increase in the rate of apoptosis induced by hypoxia. The results from the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and LDH (lactate dehydrogenase) assays indicated that cardiomyocyte injury noticeably increased after exposure to hypoxia. Meanwhile, hypoxia dramatically increased the apoptosis rate [which was reflected in the results from the annexin V – propidium iodide (PI) assay], enhanced caspase-3 activity, and reduced the expression of Bcl-2. Downregulation of miR-182-5p can significantly reverse hypoxia-induced cardiomyocyte injury or apoptosis. Importantly, bioinformatic analysis and dual-luciferase reporter assay revealed that CIAPIN1 (cytokine-induced apoptosis inhibitor 1) was a direct functional target of miR-182-5p, and that inhibition of miR-182-5p can lead to an increase in CIAPIN1 expression at both the mRNA and protein levels. Furthermore, the knockdown of CIAPIN1 with small interfering RNAs (siRNAs) efficiently abolished the protective effects of miR-182-5p inhibitor on HICA, demonstrating that miR-182-5p plays a pro-apoptotic role in cardiomyocytes under hypoxic conditions by downregulating CIAPIN1. Collectively, our results demonstrate that miR-182-5p may serve an underlying target to prevent cardiomyocytes from hypoxia-induced injury or apoptosis.

Role of NF-κB in the Rescue of Multiple Myeloma Cells From Glucocorticoid-Induced Apoptosis by Bcl-2

Blood ◽  
1999 ◽  
Vol 93 (9) ◽  
pp. 3044-3052 ◽  
Author(s):  
Rena Feinman ◽  
Jadd Koury ◽  
Michael Thames ◽  
Bart Barlogie ◽  
Joshua Epstein ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Dna Binding ◽  
Molecular Mechanisms ◽  
Annexin V ◽  
Early Event ◽  
Protective Effects ◽  
Mobility Shift ◽  
Myeloma Cells ◽  
Mobility Shift Assay ◽  
Induced Apoptosis

Abstract The molecular mechanisms by which multiple myeloma (MM) cells evade glucocorticoid-induced apoptosis have not been delineated. Using a human IgAκ MM cell line (ARP-1), we found that dexamethasone (Dex)-induced apoptosis is associated with decreased NF-κB DNA binding and κB-dependent transcription. Both nuclear p50:p50 and p50:p65 NF-κB complexes are detected in ARP-1 cells by supershift electrophoretic mobility shift assay (EMSA). Dex-mediated inhibition of NF-κB DNA binding precedes a notable increase in annexin V binding, thereby indicating that diminished NF-κB activity is an early event in Dex-induced apoptosis. Overexpression of bcl-2 in ARP-1 cells prevents Dex-mediated repression of NF-κB activity and apoptosis. Sustained NF-κB DNA binding is also observed in two previously characterized Dex-resistant MM cell lines (RPMI8226 and ARH-77) that express moderate levels of endogenous bcl-2 and IκB proteins. In addition, enforced bcl-2 expression in ARP-1 cells did not prevent the augmentation of IκB protein by Dex. We also noted a possible association between Dex-mediated downregulation of NF-κB in freshly obtained primary myeloma cells and the patients’ responsiveness to glucocorticoid-based chemotherapy. Collectively, our data suggest that the protective effects of bcl-2 in MM cells act upstream in the NF-κB activation–signaling pathway and the potential use of NF-κB as a biomarker in progressive MM.

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