Citicoline protects against lead-induced oxidative injury in neuronal PC12 cells

2019 ◽  
Vol 97 (6) ◽  
pp. 715-721 ◽  
Author(s):  
Azadeh Aminzadeh ◽  
Ayda Salarinejad
Keyword(s):  
Pc12 Cells ◽  
Caspase 3 ◽  
Neuroprotective Effect ◽  
Treated Group ◽  
Environmental Pollutant ◽  
Thiol Groups ◽  
Apoptotic Pathway ◽  
Antioxidant Power ◽  
Total Thiol ◽  
Induced Apoptosis

Lead is a major environmental pollutant that causes serious adverse effects on biological systems and cells. In this study, we examined the effect of citicoline on lead-induced apoptosis in PC12 cells. The PC12 cells were pre-treated with citicoline and then exposed to lead for 48 h. The effect of citicoline on cell survival was examined by MTT assay. In addition, levels of lipid peroxidation (LPO), total thiol groups, total antioxidant power (TAP), catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH) were evaluated. The levels of Bax, Bcl-2, and caspase-3 were also measured, by Western blot analysis. Citicoline significantly increased the cell viability of PC12 cells exposed to lead. Treatment of PC12 cells with lead increased LPO levels, and citicoline effectively decreased LPO. Levels of total thiol groups and TAP, CAT, SOD, and GSH were significantly increased in citicoline-treated PC12 cells compared with the lead-treated group. Citicoline pretreatment significantly reduced Bax expression, and increased the level of Bcl-2 expression. Citicoline also reduced caspase-3 activation in PC12 cells compared with the lead-treated group. Our findings indicate that citicoline exerts a neuroprotective effect against lead-induced injury in PC12 cells through mitigation of oxidative stress and, at least in part, through suppression of the mitochondria-mediated apoptotic pathway.

scholarly journals Neuroprotective Effect of Modified Xijiao Dihuang Decoction against Oxygen-Glucose Deprivation and Reoxygenation-Induced Injury in PC12 Cells: Involvement of TLR4-MyD88/NF-κB Signaling Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Xu Zhang ◽  
Xiaojun Fei ◽  
Weiwei Tao ◽  
Jingbo Li ◽  
Hao Shen ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Pc12 Cells ◽  
Caspase 3 ◽  
Neuroprotective Effect ◽  
Glucose Deprivation ◽  
Treated Group ◽  
Chinese Herbs ◽  
Oxygen Glucose Deprivation ◽  
Control Group ◽  
Stroke Treatment

Modified Xijiao Dihuang (XJDH) decoction has been shown to exert powerful neuroprotective properties in clinical ischemic stroke treatment. It consists of 4 Chinese herbs: Buffalo Horn, Paeonia suffruticosa Andrews, Rehmannia glutinosa (Gaertn.) DC, and Paeonia lactiflora Pall. In the present study, the neuroprotective effect and specific mechanisms of XJDH in protecting PC12 cells from oxygen-glucose deprivation-induced injury were investigated. It was found that OGD/R significantly decreased the cell viability and lactate dehydrogenase (LDH) activity and increased the release of IL-1β, IL-6, and TNF-α in PC12 cells, and these effects were suppressed by XJDH and one of its major active constituents, paeoniflorin. Additionally, XJDH inhibited caspase-3 activity and reduced cleaved caspase-3 level. Mechanistic studies showed that the expressions of TLR4, MyD88, TRAF6, and NF-κB p65 and phosphorylation of IκBα and p65 were significantly lower in the XJDH-treated group than in the OGD/R control group. Additionally, XJDH reversed the OGD/R-induced increases in p-JNK and p-ERK1/2 expression. These results suggest that XJDH protects PC12 cells from oxygen-glucose deprivation-induced injury, which may be associated with the inhibition of the TLR4-MyD88/NF-κB signaling pathway. As an anti-inflammation factor, XJDH might be used as a neuronal protection strategy for the ischemia injury and related diseases.

scholarly journals Ginsenoside Rb1 Prevents MPP+-Induced Apoptosis in PC12 Cells by Stimulating Estrogen Receptors with Consequent Activation of ERK1/2, Akt and Inhibition of SAPK/JNK, p38 MAPK

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Ryo Hashimoto ◽  
Jing Yu ◽  
Hideki Koizumi ◽  
Yasuyoshi Ouchi ◽  
Tetsuro Okabe
Keyword(s):  
Estrogen Receptor ◽  
Pc12 Cells ◽  
Dna Fragmentation ◽  
Caspase 3 ◽  
Neuroprotective Effect ◽  
Ginsenoside Rb1 ◽  
Neuroprotective Effects ◽  
Induced Apoptosis ◽  
Sb 203580 ◽  
Stimulation Of

Ginsenoside Rb1 shows neuroprotective effects in various neurons, including dopaminergic cells. However, the precise mechanisms of action are uncertain. In this paper, we examine whether Rb1 has a neuroprotective effect on MPP+-induced apoptosis and attempt to clarify the signaling pathway in PC12 cells. Apoptosis of PC12 cells was determined by DNA fragmentation assay, the activation of caspase-3, or by the inactivation of Bcl-xL. Rb1 inhibited MPP+-induced caspase-3 activation and DNA fragmentation and activated Bcl-xL in MPP+-treated PC12 cells. These antiapoptotic effect was abrogated in PC12 cells transfected with estrogen receptor siRNA. Levels of DNA fragmentation were increased by wortmannin or PD 98059, while they were decreased by SB 203580 or SP 600125 in MPP+-treated PC12 cells. Rb1 increased phosphorylation levels of ERK1/2 or Akt in MPP+-treated PC12 cells, while it reduced phosphorylated p38 or SAPK/JNK. The increased phosphorylation of ERK/1/2 or Akt by Rb1 was abrogated by estrogen receptor siRNA. Rb1-induced inhibition of SAPK/JNK or p38 phosphorylation was also abolished by estrogen receptor siRNA. These results suggest that ginsenoside Rb1 protects PC12 cells from caspase-3-dependent apoptosis through stimulation of estrogen receptor with consequent activation of ERK1/2 and Akt and inhibition of SAPK/JNK and p38.

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.

Identification of apoptotic genes mediating TGF-β/Smad3-induced cell death in intestinal epithelial cells using a genomic approach

2007 ◽  
Vol 292 (1) ◽  
pp. G28-G38 ◽  
Author(s):  
Yanna Cao ◽  
Lu Chen ◽  
Weili Zhang ◽  
Yan Liu ◽  
Harry T. Papaconstantinou ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Intestinal Epithelial ◽  
Cytochrome C Release ◽  
Apoptotic Pathway ◽  
Genomic Approach ◽  
Apoptotic Genes ◽  
Induced Apoptosis

Transforming growth factor (TGF)-β-dependent apoptosis is important in the elimination of damaged or abnormal cells from normal tissues in vivo. Previously, we have shown that TGF-β inhibits the growth of rat intestinal epithelial (RIE)-1 cells. However, RIE-1 cells are relatively resistant to TGF-β-induced apoptosis due to a low endogenous Smad3-to-Akt ratio. Overexpression of Smad3 sensitizes RIE-1 cells (RIE-1/Smad3) to TGF-β-induced apoptosis by altering the Smad3-to-Akt ratio in favor of apoptosis. In this study, we utilized a genomic approach to identify potential downstream target genes that are regulated by TGF-β/Smad3. Total RNA samples were analyzed using Affymetrix oligonucleotide microarrays. We found that TGF-β regulated 518 probe sets corresponding to its target genes. Interestingly, among the known apoptotic genes included in the microarray analyses, only caspase-3 was induced, which was confirmed by real-time RT-PCR. Furthermore, TGF-β activated caspase-3 through protein cleavage. Upstream of caspase-3, TGF-β induced mitochondrial depolarization, cytochrome c release, and cleavage of caspase-9, which suggests that the intrinsic apoptotic pathway mediates TGF-β-induced apoptosis in RIE-1/Smad3 cells.

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

2002 ◽  
Vol 45 (4) ◽  
pp. 135-144 ◽  
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.

Delayed effects of autophagy on T-2 toxin-induced apoptosis in mouse primary Leydig cells

2019 ◽  
Vol 35 (3) ◽  
pp. 256-263 ◽  
Author(s):  
Jian Ying Yang ◽  
Yong Fa Zhang ◽  
Xiang Ping Meng ◽  
Xiang Feng Kong
Keyword(s):  
Cross Talk ◽  
Leydig Cells ◽  
Caspase 3 ◽  
Treated Group ◽  
Testicular Toxicity ◽  
Reproductive Disorders ◽  
Delayed Effects ◽  
Food Commodities ◽  
Induced Apoptosis ◽  
High Level

T-2 toxin is a type-A trichothecene produced by Fusarium found in several food commodities worldwide. T-2 toxin causes reproductive disorders, genotoxicity, and testicular toxicity in animals. Our previous research has reported that T-2 toxin can induce apoptosis via the Bax-dependent caspase-3 activation in mouse primary Leydig cells. However, little is known about the functions of autophagy and the cross talk between autophagy and apoptosis after exposure to T-2 toxin in Leydig cells. This study investigated these problems in mouse primary Leydig cells. Results showed that T-2 toxin treatment upregulated LC3-II and Beclin-1 expression, suggesting that T-2 toxin induced a high level of autophagy. Pretreatment with chloroquine (an autophagy inhibitor) and rapamycin (an autophagy inducer) increased and decreased the rate of apoptosis, respectively, in contrast to T-2 toxin-treated group. Autophagy delayed apoptosis in the T-2 toxin-treated Leydig cells. Therefore, autophagy may prevent cells from undergoing apoptosis by reducing T-2 toxin-induced cytotoxicity.

Astaxanthin prevents lung injury due to hyperoxia and inflammation

2020 ◽  
Vol 23 ◽  
Author(s):  
Hasan Akduman ◽  
Cüneyt Tayman ◽  
Ufuk Çakir ◽  
Esra Çakir ◽  
Dilek Dilli ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Interleukin 1 ◽  
Survival Rates ◽  
Lipid Hydroperoxide ◽  
Treated Group ◽  
Lung Damage ◽  
Pregnant Rats ◽  
Necrosis Factor Alpha ◽  
Total Thiol ◽  
Tnf Α

Background/aim: We aimed to ascertain the effects of astaxanthin on the lungs of rat pups with bronchopulmonary dysplasia (BPD) induced by hyperoxia and lipopolysaccharide (LPS). Materials and methods: Forty-two newborn Wistar rats born to spontaneous pregnant rats were divided into three groups: Hyperoxia (95% O2) + lipopolysaccharide (LPS) group, hyperoxia + LPS + astaxhantin group and control: no treatment group (21% O2). Pups in the hyperoxia + LPS + astaxanthin group were given 100 mg/kg/day oral astaxanthin from the first day to the fifth day. Histopathologic and biochemical evaluations including glutathione (GSH), total antioxidant status (TAS), total oxidant status (TOS), lipid hydroperoxide (LPO), 8-hydroxydeoxyguanosine (8-OHdG), advanced oxidation protein products (AOPP), myeloperoxidase (MPO), total thiol, tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL1β) and caspase-3 activities were performed. Results: A better survival rates and weight gain were demonstrated in the hyperoxia + LPS + astaxanthin group (p <0.001). In the histopathologic evaluation, the severity of lung damage was significantly reduced in the hyperoxia+LPS+astaxanthin group, as well as decreased apoptosis (ELİSA for caspase-3) (p <0.001). The biochemical analyses of lung tissues TAS, GSH, Total thiol levels were significantly higher in the astaxanthin treated group compared to hyperoxia + LPS group (p <0.05) while TOS, AOPP, LPO, 8-OHdG, MPO levels were significantly lower (p <0.001). In addition, unlike the hyperoxia + LPS group, TNF-α and IL-1β levels in lung tissue were significantly lower in the astaxanthin-treated group (p <0.001). Conclusion: Astaxanthin was shown to reduce lung damage caused by inflammation and hyperoxia with its antiinflammatory, anti-oxidant, anti-apoptotic properties and to protect the lung from severe destruction.

Synthesis of 5-Alkynyltetrandrine Derivatives and Evaluation of their Anticancer Activity on A549 Cell Lines

2019 ◽  
Vol 19 (12) ◽  
pp. 1454-1462 ◽  
Author(s):  
Nana Niu ◽  
Tingli Qu ◽  
Jinfang Xu ◽  
Xiaolin Lu ◽  
Graham J. Bodwell ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Caspase 3 ◽  
Human Lung ◽  
A549 Cells ◽  
Human Lung Cancer ◽  
Coupling Reactions ◽  
Apoptotic Pathway ◽  
Future Design ◽  
Cyt C ◽  
Induced Apoptosis

Background: Lung cancer is one of the most prevalent malignancies and thus the development of novel therapeutic agents for managing lung cancer is imperative. Tetrandrine, a bis-benzyltetrahydroisoquinoline alkaloid isolated from Stephania tetrandra S. Moore, has been found to exert cytotoxic effects on cancerous cells. Methods: A series of 5-alkynyltetrandrine derivatives was synthesized via the Sonogashira cross-coupling reactions and evaluated as potential anti-tumor agents. The anti-tumor activities of 12 compounds on lung cancer cells (A549) were evaluated using the MTT method. The population of apoptotic cells was measured using a TUNEL assay. Real-time PCR quantified the gene expression levels of Bcl-2, Bax, survivin and caspase-3. The content of Cyt-C was detected using a Human Cyt-C ELISA kit. Results: Most of these compounds exhibited better activities than tetrandrine itself on A549 cells. Among them, compound 7 showed the highest cytotoxicity among the tested compounds against human lung adenocarcinoma A549 cells with an IC50 of 2.94 µM. Preliminary mechanistic studies indicated that compound 7 induced apoptosis of human lung cancer A549 cells and increased the level of the proapoptotic gene Bax, release of Cyt-C from mitochondria and activation of caspase-3 genes. Conclusion: The results suggest that compound 7 exerts its antitumor activity against A549 cells through the induction of the intrinsic (mitochondrial) apoptotic pathway. These findings will contribute to the future design of more effective anti-tumor agents in lung cancer therapy.

Crocin protects against beta-amyloid peptide-induced apoptosis in PC12 cells via PI3 K pathway

2020 ◽  
Vol 13 ◽  
Author(s):  
Reyhaneh Taheri ◽  
Elham Hadipour ◽  
Zahra Tayarani-Najaran
Keyword(s):  
Pc12 Cells ◽  
Caspase 3 ◽  
Beta Amyloid ◽  
Pi3 Kinase ◽  
Amyloid Peptide ◽  
Ros Generation ◽  
Protective Effects ◽  
Beta Amyloid Peptide ◽  
Cyt C ◽  
Induced Apoptosis

Background: Crocin is a known compound with antioxidant and anti-inflammatory property which many help to reduce the progression of neurological disorders. In this study, we aimed to investigate the protective effects of crocin on beta-amyloid peptide Aβ (1-40) and hydrogen peroxide (H2O2) induced neurotoxicity in PC12 cells. Methods: PC12 cells pretreated with crocin and donepezil (5 and 10 µM) for 2 h then treated with Aβ (1-40) (25 µM) for 24 h. In parallel after pretreatment with crocin (5 and 10 µM) and donepezil (5 and 10 µM) for 24 h, cells were treated with H2O2 (800 µM) for 4 h. Finally, the cell viability and intracellular reactive oxygen species (ROS) generation were evaluated using AlamarBlue® and 2', 7'-dichlorodihydrofluorescein diacetate (DCFH-DA), respectively. The western blot test was done to compare the protein level of phospho SAPK/JNK, SAPK/JNK, PI3 Kinase P85, Phospho-PI3 Kinase P85, caspase-3 and cytochrome c )cyt c). Results: Crocin and donepezil could significantly decrease the Aβ toxicity and ROS level. While treatment with Aβ increased Cyt c release from mitochondria to cytosol, cleaved form of caspase-3 (17 kDa) and activated form of SAPK/JNK p44/4 and decreased the activated form of PI3 Kinase P85 protein, crocin could significantly block the apoptosis initiated with Aβ. Conclusions: According to the results crocin could be a promising candidate for further evaluations against the development of Alzheimer's diseases through mitogen-activated protein kinases (MAPK) and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling (PI3 K/AKT) pathways.

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