The effect of caspase-3 in mitochondrial apoptosis activation on degradation of structure proteins of Esox lucius during postmortem storage

2021 ◽  
pp. 130767
Author(s):  
Xue Li ◽  
Ling Hu ◽  
Xinrong Zhu ◽  
Xiaobing Guo ◽  
Xiaorong Deng ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Esox Lucius ◽  
Mitochondrial Apoptosis ◽  
Degradation Of Structure

scholarly journals Iron overload induced death of osteoblasts in vitro: involvement of the mitochondrial apoptotic pathway

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2611 ◽  
Author(s):  
Qing Tian ◽  
Shilei Wu ◽  
Zhipeng Dai ◽  
Jingjing Yang ◽  
Jin Zheng ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Iron Overload ◽  
Caspase 3 ◽  
Osteoblastic Cell ◽  
Ferric Ion ◽  
Oxygen Species ◽  
Mitochondrial Apoptosis ◽  
Apoptotic Pathway ◽  
Mitochondrial Apoptotic Pathway ◽  
Commercial Kits

BackgroundIron overload is recognized as a new pathogenfor osteoporosis. Various studies demonstrated that iron overload could induce apoptosis in osteoblasts and osteoporosis in vivo. However, the exact molecular mechanisms involved in the iron overload-mediated induction of apoptosis in osteoblasts has not been explored.PurposeIn this study, we attempted to determine whether the mitochondrial apoptotic pathway is involved in iron-induced osteoblastic cell death and to investigate the beneficial effect of N-acetyl-cysteine (NAC) in iron-induced cytotoxicity.MethodsThe MC3T3-E1 osteoblastic cell line was treated with various concentrations of ferric ion in the absence or presence of NAC, and intracellular iron, cell viability, reactive oxygen species, functionand morphology changes of mitochondria and mitochondrial apoptosis related key indicators were detected by commercial kits. In addition, to further explain potential mechanisms underlying iron overload-related osteoporosis, we also assessed cell viability, apoptosis, and osteogenic differentiation potential in bone marrow-derived mesenchymal stemcells(MSCs) by commercial kits.ResultsFerric ion demonstrated concentration-dependent cytotoxic effects on osteoblasts. After incubation with iron, an elevation of intracelluar labile iron levels and a concomitant over-generation of reactive oxygen species (ROS) were detected by flow cytometry in osteoblasts. Nox4 (NADPH oxidase 4), an important ROS producer, was also evaluated by western blot. Apoptosis, which was evaluated by Annexin V/propidium iodide staining, Hoechst 33258 staining, and the activation of caspase-3, was detected after exposure to iron. Iron contributed to the permeabilizatio of mitochondria, leading to the release of cytochrome C (cyto C), which, in turn, induced mitochondrial apoptosis in osteoblasts via activation of Caspase-3, up-regulation of Bax, and down-regulation of Bcl-2. NAC could reverse iron-mediated mitochondrial dysfunction and blocked the apoptotic events through inhibit the generation of ROS. In addition, iron could significantly promote apoptosis and suppress osteogenic differentiation and mineralization in bone marrow-derived MSCs.ConclusionsThese findings firstly demonstrate that the mitochondrial apoptotic pathway involved in iron-induced osteoblast apoptosis. NAC could relieved the oxidative stress and shielded osteoblasts from apoptosis casused by iron-overload. We also reveal that iron overload in bone marrow-derived MSCs results in increased apoptosis and the impairment of osteogenesis and mineralization.

scholarly journals Gan-Qing-Ning Formula Inhibits the Growth of Hepatocellular Carcinoma by Promoting Apoptosis and Inhibiting Angiogenesis in H22 Tumor-Bearing Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Fan-Yan Zeng ◽  
Kai-Li Zhao ◽  
Le-Zhen Lin ◽  
Ying Deng ◽  
Si Qin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Antitumor Effect ◽  
Caspase 3 ◽  
Tumor Tissue ◽  
Mitochondrial Apoptosis ◽  
Apoptosis Pathway ◽  
Expression Levels ◽  
Mitochondrial Apoptosis Pathway ◽  
Tumor Bearing ◽  
Mrna Expression Levels

Objective. Gang-Qing-Ning (GQN) is a traditional Chinese medicine formula that has been used in the treatment of hepatocellular carcinoma (HCC) in the folk population for decades. However, scientific validation is still necessary to lend credibility to the traditional use of GQN against HCC. This study investigates the antitumor effect of GQN on H22 tumor-bearing mice and its possible mechanism. Methods. Fifty H22 tumor-bearing mice were randomly assigned to five groups. Three groups were treated with high, medium, and low dosages of GQN (27.68, 13.84, and 6.92 g/kg, respectively); the positive control group was treated with cytoxan (CTX) (20 mg/kg) and the model group was treated with normal saline. After 10 days’ treatment, the tumor inhibitory rates were calculated. Pathological changes in tumor tissue were observed, and the key proteins and genes of the mitochondrial apoptosis pathway were measured, as well as the mRNA expression levels of VEGF in tumor tissue. Results. The tumor inhibitory rates of high, medium, and low dosages of GQN groups were 47.39%, 38.26%, and 22.17%, respectively. The high dosage of the GQN group significantly increased the protein and mRNA expression levels of Bax, Cyt-C, and cleaved Caspase 3 (or Caspase 3) (P<0.01) but decreased the expression levels of Bcl-2, VEGF, and microvessel density (MVD) (P<0.01). Conclusions. The high dosage of GQN can significantly inhibit the tumor growth in H22 tumor-bearing mice. It exerts the antitumor effect by enhancing proapoptotic factors and inhibiting the antiapoptotic factor of the mitochondrial apoptosis pathway and inhibiting tumor angiogenesis.

scholarly journals Gasdermine E-Dependent Mitochondrial Pyroptotic Pathway in Dermatomyositis: A Possible Mechanism of Perifascicular Atrophy

2020 ◽  
Vol 79 (5) ◽  
pp. 551-561
Author(s):  
Meirong Liu ◽  
Ling Li ◽  
Tingjun Dai ◽  
Ying Hou ◽  
Wei Li ◽  
...  
Keyword(s):  
Cell Death ◽  
Caspase 3 ◽  
Immunohistochemical Analysis ◽  
Positive Staining ◽  
Mrna Levels ◽  
Mitochondrial Apoptosis ◽  
Histologic Feature ◽  
Caspase 9 ◽  
Perifascicular Atrophy ◽  
And Control

Abstract Different mechanisms have been proposed to explain the pathological basis of perifascicular atrophy (PFA), a pathognomonic histologic feature of dermatomyositis (DM); however, the detailed mechanisms remain to be elucidated. There is mitochondrial dysfunction in PFA and expression of mitochondrial apoptosis molecules has been reported in DM. Overexpression of gasdermin E (GSDME) can turn mitochondrial apoptosis to mitochondrial pyroptosis, a newly characterized form of programmed cell death. We determined the expression of proteins involved in the caspase-3- and GSDME-dependent mitochondrial pyroptotic pathway, including BAX, BAK, cytochrome C, caspase-9, caspase-3, GSDME, and IL-1α, in biopsied muscles from DM and control patients. Immunohistochemical analysis showed that those markers were expressed in most fibers in PFA in DM. GSDME-positive and IL-1α-positive staining was mainly localized around punched-out vacuoles or sarcolemma. These markers were significantly upregulated at the protein and mRNA levels in DM versus controls. Our results suggest that caspase-3- and GSDME-dependent mitochondrial pyroptosis are involved in the pathogenetic mechanisms of PFA in DM and that targeting GSDME-dependent mitochondrial pyroptosis may be an effective therapeutic approach for this condition.

Photodynamic Effects of Vitamin K3 on Cervical Carcinoma Cells Activating Mitochondrial Apoptosis Pathways

2020 ◽  
Vol 21 (1) ◽  
pp. 91-99
Author(s):  
Yong Xin ◽  
Wenwen Guo ◽  
Chunsheng Yang ◽  
Qian Huang ◽  
Pei Zhang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Mitochondrial Apoptosis ◽  
Caspase 9 ◽  
Vitamin K3 ◽  
Cervical Cancer Cells ◽  
Apoptosis Pathways

Background: Photodynamic Therapy (PDT) is a photoactivation or photosensitization process, wherein vitamin K3 (Vit K3) serves as a photosensitizer to produce Reactive Oxygen Species (ROS) against bacteria at appropriate wavelengths. In this study, we used Vit K3 treatment combined with Ultraviolet radiation A (UVA) to produce photodynamic effects on cervical cancer. Methods: The dose-concentration relationship between Vit K3 treatment and UVA on tumor cells was analyzed through the Cell Counting Kit-8 method. Then, the morphological characteristics of apoptosis cells were observed through fluorescent staining and fluorescence microscopy. Apoptosis after treatment with Vit K3 treatment, UVA, and Vit K3 treatment plus UVA was further observed through Western blot analysis, flow cytometry, and TUNEL assay. The xenograft models from HeLa cells were established for the exploration of the photodynamic effect of Vit K3 treatment on cervical cancer in vivo. Results: Vit K3 treatment plus UVA reduced tumor cell viability in a dose-dependent manner. Further studies indicated that Vit K3 treatment plus UVA can inhibit tumor growth and enhance the apoptosis of cervical cancer cells. In the combination group, the expression levels of cleaved caspase-3, cleaved caspase-9, B-cell lymphoma- extra large (Bcl-xl), and cytochrome c (cyt-c) increased obviously, whereas the expression level of Bcell lymphoma 2 (Bcl-2) decreased relative to the expression levels of UVA- or Vit K3-treated cells. In the in vivo experiments, tumor growth was inhibited significantly in the VitK3 treatment plus UVA group. Additionally, we demonstrated that the combination therapy mediated an increase in cleaved caspase-3 and cleaved caspase-9 expression and decrease in Bcl-2 expression in vivo. Conclusion: Our results showed that Vit K3 treatment combined with UVA exerted photodynamic effects on cervical cancer cells by activating mitochondrial apoptosis pathways.

scholarly journals The 19 kDaMycobacterium tuberculosisLipoprotein (LpqH) Induces Macrophage Apoptosis through Extrinsic and Intrinsic Pathways: A Role for the Mitochondrial Apoptosis-Inducing Factor

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Alejandro Sánchez ◽  
Patricia Espinosa ◽  
Teresa García ◽  
Raúl Mancilla
Keyword(s):  
Caspase 3 ◽  
Transmembrane Potential ◽  
Death Receptor ◽  
Signaling Cascade ◽  
Mitochondrial Apoptosis ◽  
Caspase 9 ◽  
Macrophage Apoptosis ◽  
Tlr2 Activation ◽  
Death Receptor Signaling ◽  
Apoptosis Inducing Factor

We describe the association of caspase-dependent and caspase-independent mechanisms in macrophage apoptosis induced by LpqH, a 19 kDaMycobacterium tuberculosislipoprotein. LpqH triggered TLR2 activation, with upregulation of death receptors and ligands, which was followed by a death receptor signaling cascade with activation of initiator caspase 8 and executioner caspase 3. In this caspase-mediated phase, mitochondrial factors were involved in loss of mitochondrial transmembrane potential (ΔΨm), release of cytochrome c, and caspase 9 activation. Interestingly, a caspase-independent pathway was also identified; by immunoblot, the mitochondrial apoptosis inducing factor (AIF) was demonstrated in nuclei and cytosol of LpqH-treated macrophages. Confocal microscopy revealed translocation of AIF to the nuclei of the majority of apoptotic cells. These findings emphasize the complex and redundant nature of the macrophage death response to mycobacteria.

scholarly journals Conditioned Medium of Adipose-Derived Mesenchymal Stem Cells as a Promising Candidate to Protect High Glucose-Induced Injury in Cultured C28I2 Chondrocytes

2021 ◽  
Author(s):  
Sedighe Safari ◽  
Akram Eidi ◽  
Mehrnaz Mehrabani ◽  
Mohammad Javad Fatemi ◽  
Ali Mohammad Sharifi
Keyword(s):  
Lipid Peroxidation ◽  
Conditioned Medium ◽  
High Glucose ◽  
Caspase 3 ◽  
Thiobarbituric Acid ◽  
Heme Oxygenase 1 ◽  
Diabetic Patients ◽  
Mitochondrial Apoptosis ◽  
Paracrine Effects ◽  
Protein Levels

Purpose: The aim of this study was to evaluate the protective effect of conditioned medium derived from human adipose MSCs (CM-hADSCs) on C28I2 chondrocytes against oxidative stress and mitochondrial apoptosis induced by high glucose (HG). Methods: C28I2 cells were pre-treated with CM-hADSCs for 24 hours followed by HG exposure (75 mM) for 48 hours. MTT assay was used to assess the cell viability. Reactive oxygen species (ROS) and lipid peroxidation were determined by 2,7-dichlorofluorescein diacetate (DCFH-DA) and thiobarbituric acid reactive substances (TBARS) assays, respectively. Expressions of glutathione peroxidase 3 (GPX 3), heme oxygenase-1 (HO-1), and NAD(P)H quinone dehydrogenase 1 (NQO1) were analyzed by RT-PCR. Finally, western blot analysis was used to measure Bax, Bcl-2, cleaved caspase-3, and Nrf-2 expression at protein levels. Results: CM-hADSCs pretreatment mitigated the cytotoxic effect of HG on C28I2 viability. Treatment also markedly reduced the levels of ROS, lipid peroxidation, and augmented the expression of HO-1, NQO1, and GPx3 genes in HG-exposed group. CM-ADSCs enhanced Nrf-2 protein expression and reduced mitochondrial apoptosis through reducing Bax/Bcl-2 ratio and Caspase-3 activation. Conclusion: MSCs, probably through its paracrine effects, declined the deleterious effect of HG on chondrocytes. Hence, therapies based on MSCs secretomes appear to be a promising therapeutic approaches to prevent joint complications in diabetic patients.

scholarly journals Protective Effect of N-Acetylcysteine against Oxidative Stress Induced by Zearalenone via Mitochondrial Apoptosis Pathway in SIEC02 Cells

Toxins ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 407 ◽  
Author(s):  
Jingjing Wang ◽  
Mengmeng Li ◽  
Wei Zhang ◽  
Aixin Gu ◽  
Jiawen Dong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Messenger Rna ◽  
Caspase 3 ◽  
Intestinal Epithelial ◽  
Mitochondrial Apoptosis ◽  
Caspase 9 ◽  
Treatment Results ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway ◽  
Small Intestinal

Zearalenone (ZEN), a nonsteroidal estrogen mycotoxin, is widely found in feed and foodstuffs. Intestinal cells may become the primary target of toxin attack after ingesting food containing ZEN. Porcine small intestinal epithelial (SIEC02) cells were selected to assess the effect of ZEN exposure on the intestine. Cells were exposed to ZEN (20 µg/mL) or pretreated with (81, 162, and 324 µg/mL) N-acetylcysteine (NAC) prior to ZEN treatment. Results indicated that the activities of glutathione peroxidase (Gpx) and glutathione reductase (GR) were reduced by ZEN, which induced reactive oxygen species (ROS) and malondialdehyde (MDA) production. Moreover, these activities increased apoptosis and mitochondrial membrane potential (ΔΨm), and regulated the messenger RNA (mRNA) expression of Bax, Bcl-2, caspase-3, caspase-9, and cytochrome c (cyto c). Additionally, NAC pretreatment reduced the oxidative damage and inhibited the apoptosis induced by ZEN. It can be concluded that ZEN-induced oxidative stress and damage may further induce mitochondrial apoptosis, and pretreatment of NAC can degrade this damage to some extent.

scholarly journals Taxifolin protects rat against myocardial ischemia/reperfusion injury by modulating the mitochondrial apoptosis pathway

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6383 ◽  
Author(s):  
Zhenqiu Tang ◽  
Chunjuan Yang ◽  
Baoyan Zuo ◽  
Yanan Zhang ◽  
Gaosong Wu ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Caspase 3 ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Mitochondrial Apoptosis ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway ◽  
Myocardial Apoptosis ◽  
Cyt C ◽  
Myocardial Ischemia Reperfusion

Background Taxifolin (TAX), is an active flavonoid, that plays an underlying protective role on the cardiovascular system. This study aimed to evaluate its effect and potential mechanisms on myocardial ischemia/reperfusion (I/R) injury. Methods Healthy rat heart was subjected to I/R using the Langendorff apparatus. Hemodynamic parameters, including heart rate, left ventricular developed pressure (LVDP), maximum/minimum rate of the left ventricular pressure rise (+dp/dtmax and −dp/dtmin) and rate pressure product (RPP) were recorded during the perfusion. Histopathological examination of left ventricular was measured by hematoxylin-eosin (H&E) staining. Creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) activities in the effluent perfusion, and the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) in the tissue were assayed. Apoptosis related proteins, such as B-cell lymphoma-2 (Bcl-2), Bcl2-associated X (Bax), and cytochrome c (Cyt-c) were also assayed by ELISA. Western blot was employed to determine apoptosis-executive proteins, including caspase 3 and 9. Transferase-mediated dUTP-X nick end labeling assay was performed to evaluate the effect TAX on myocardial apoptosis. Results Taxifolin significantly improved the ventricular functional recovery, as evident by the increase in LVDP, +dp/dtmax, −dp/dtmin and RPP, the levels of SOD, GSH-PX were also increased, but those of LDH, CK-MB, and MDA were decreased. Furthermore, TAX up-regulated the Bcl-2 protein level but down-regulated the levels of Bax, Cyt-c, caspase 3 and 9 protein, thereby inhibits the myocardial apoptosis. Discussion Taxifolin treatment remarkably improved the cardiac function, regulated oxidative stress and attenuated apoptosis. Hence, TAX has a cardioprotective effect against I/R injury by modulating mitochondrial apoptosis pathway.

scholarly journals The effect of GSK-3β in arsenic-induced apoptosis of malignant tumor cells: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Xin Gao ◽  
Bin Deng ◽  
Shanshan Ran ◽  
Shugang Li
Keyword(s):  
Tumor Cell ◽  
Malignant Tumor ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Meta Analysis ◽  
Mitochondrial Apoptosis ◽  
Apoptosis Pathway ◽  
Tumor Cell Apoptosis ◽  
Mitochondrial Apoptosis Pathway ◽  
Gsk 3Β

Abstract Purpose: Arsenic has been reported to induce apoptosis in malignant tumor cells, therefore, it may be regarded as a treatment for some cancers. The mitochondrial apoptosis pathway, mediated by GSK-3β, plays an important role in tumor cell apoptosis. Nonetheless, the regulation of GSK-3β by arsenic remains controversial. Materials and Methods: We included 19 articles, which conducts the role of GSK-3β in the process of arsenic-induced tumor cell apoptosis by the meta-analysis. Results: Compared with the control group, the expression of GSK-3β (SMD=-0.92,95% CI (-1.78,-0.06)), p-Akt (SMD=-5.46,95% CI (-8.67,-2.24)) were reduced in the arsenic intervention group. Meanwhile, the combined treatment of arsenic and Akt agonist can inhibit the expression of p-GSK-3β. Using the dose and time subgroup analysis, it was shown that the low-dose and sub-chronic arsenic exposure could inhibit the expression of p-Akt (P<0.05). In the subgroup analysis of GSK-3β sites, arsenic could inhibit p-Akt and GSK-3β (Ser9) (SMD =-0.95, 95% CI (-1.56,-0.33)). There was a dose-related effect seen between arsenic (≤8 μmol/L) and p-GSK-3β, and the expression of p-GSK-3β was gradually followed by the arsenic dose. When arsenic acted on GSK-3β (ser9), the expression of Mcl-1 and pro-caspase-3 were dropped, while the loss rate of mitochondrial membrane potential and cleaved-caspase-3 were increased significantly (P<0.05). Conclusion: This study revealed that arsenic could inhibit the expression of GSK-3β (Ser9) and then induce tumor cell apoptosis. It might be correlated with arsenic inhibiting p-Akt, down-regulating GSK-3β, and triggering the Mcl-1-mediated mitochondrial apoptosis pathway.

scholarly journals Modulations of Histone Deacetylase 2 Offer a Protective Effect through the Mitochondrial Apoptosis Pathway in Acute Liver Failure

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Yao Wang ◽  
Fan Yang ◽  
Fang-Zhou Jiao ◽  
Qian Chen ◽  
Wen-Bin Zhang ◽  
...  
Keyword(s):  
Liver Failure ◽  
Histone Deacetylase ◽  
Liver Tissue ◽  
Caspase 3 ◽  
Mitochondrial Apoptosis ◽  
Caspase 9 ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway ◽  
Histone Deacetylase 2 ◽  
Cyt C

The purpose of this study was to investigate the modulation of histone deacetylase 2 (HDAC2) on mitochondrial apoptosis in acute liver failure (ALF). The cellular model was established with LO2 cells stimulated by tumor necrosis factor alpha (TNF-α)/D-galactosamine (D-gal). Rats were administrated by lipopolysaccharide (LPS)/D-gal as animal model. The cell and animal models were then treated by HDAC2 inhibitor CAY10683. HDAC2 was regulated up or down by lentiviral vector transfection in LO2 cells. The mRNA levels of bcl2 and bax were detected by real-time PCR. The protein levels of HDAC2, bcl2, bax, cytochrome c (cyt c) in mitochondrion and cytosol, apoptosis protease activating factor 1 (apaf1), caspase 3, cleaved-caspase 3, caspase 9, cleaved-caspase 9, acetylated histone H3 (AH3), and histone H3 (H3) were assayed by western blot. Apoptosis was detected by flow cytometry. The serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) levels were also assayed. The openness degree of the mitochondrial permeability transition pore (MPTP) was detected by ultraviolet spectrophotometry. The apoptosis of hepatocytes in liver tissues was determined by tunnel staining. The liver tissue pathology was detected by hematoxylin eosin (HE) staining. The ultrastructure of liver tissue was observed by electron microscopy. Compared with cell and rat model groups, the bax mRNA level was decreased, and bcl2 mRNA was increased in the CAY10683 treatment group. The protein levels of HDAC2, bax, cyt c in cytosol, apaf1, cleaved-caspase 3, and cleaved-caspase 9 were decreased, and the apoptosis rate was decreased (P<0.05), whereas the protein level of bcl2 and cyt c in the mitochondrion was elevated (P<0.05) in the CAY10683 treatment group. In the HDAC2 down- or upregulated LO2 cells, the mitochondrial apoptosis pathway was inhibited or activated, respectively. After being treated with TNF-α/D-gal in HDAC2 down- or upregulated LO2 cells, the mitochondrial apoptosis pathway was further suppressed or activated, respectively. The MPTP value was elevated in CAY10683-treated groups compared with the rat model group (P<0.05). Liver tissue pathological damage and apoptotic index in the CAY10683-treated group were significantly reduced. In addition, AH3 was elevated in both cell and animal model groups (P<0.05). Downregulated or overexpressed HDAC2 could accordingly increase or decrease the AH3 level, and TNF-α/D-gal could enhance the acetylation effect. These results suggested that modulations of histone deacetylase 2 offer a protective effect through the mitochondrial apoptosis pathway in acute liver failure.

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