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.

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 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.

Biological characteristics of renal cancer cells after CTP-mediated cancer suppressor gene NPRL2 protein treatment

2016 ◽  
Vol 397 (11) ◽  
pp. 1163-1171 ◽  
Author(s):  
Yang Zeng ◽  
Xiao-Bo Shi ◽  
Zheng-Yong Yuan ◽  
Mao Ye ◽  
Li Jiang ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Renal Cancer ◽  
Caspase 3 ◽  
Cancer Cell Line ◽  
Suppressor Gene ◽  
Migration Ability ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway ◽  
Cyt C

Abstract Nitrogen permease regulator like-2 (NPRL2) has been proved to be a useful suppressor gene in treating many cancers containing renal cancer based on experiments. Transgenic technology which transfect exogenous NPRL2 gene into cancer cell was used in these experiments. However, this technology has defects, such as gene mutation and loss. Cytoplasmic transduction peptide (CTP) can be used to avoid these defects because it can directly mediate proteins to penetrate cell membrane and specifically locate in cytoplasm. In this article, CTP was used to directly mediate NPRL2 protein into the renal cancer cell line 786-O, then cell proliferation was detected by the CCK-8 method, cell cycle and apoptosis were detected by flow cytometry, cell invasion and migration ability were detected by the Transwell assay. Bcl-xl, Cyt-c and caspase-3 were detected by real-time fluorescent quantitative PCR and Western blot for the analysis of the related mechanism. The result showed that CTP successfully mediated NPRL2 protein into renal cancer cells and the growth of cells was significantly inhibited. The mechanism may be NPRL2 down-regulating the expression of Bcl-xl which can up-regulate Cyt-c and further activate caspase-3, and then a cascade reaction is caused for cell apoptosis on the classic mitochondrial apoptosis pathway.

scholarly journals Protective Effects and Mechanisms of Dendrobium nobile Lindl. Alkaloids on PC12 Cell Damage Induced by Aβ25-35

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yuan Liu ◽  
Tingting Pi ◽  
Xiaohui Yang ◽  
Jingshan Shi
Keyword(s):  
Oxidative Stress ◽  
Pc12 Cell ◽  
Caspase 3 ◽  
Cell Damage ◽  
Protective Effects ◽  
Related Protein ◽  
Caspase 9 ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway ◽  
Dendrobium Nobile Lindl

Background. Aβ deposition abnormally in the mitochondria can damage the mitochondrial respiratory chain and activate the mitochondrial-mediated apoptosis pathway, resulting in AD-like symptoms. Objective. To observe the protective effects of Dendrobium nobile Lindl. alkaloids (DNLA) on Aβ25-35-induced oxidative stress and apoptosis in PC12 cells explore its possible protective mechanisms. Methods. PC12 cells were treated with DNLA with different concentrations (0.035 mg/L, 0.3 mg/L, and 3.5 mg/L) for 6 h, followed by administration with Aβ25-35 (10 μM) for 24 h. MTT assay and flow cytometer observe the effect of DNLA on Aβ25-35-induced cytotoxicity and apoptosis of PC12 cell. Based on the mitochondrial apoptosis pathway to study the antiapoptotic effect of DNLA on this model and its relationship with oxidative stress, flow cytometer detected the level of reactive oxygen species (ROS), and ELISA kits were used to detect superoxide dismutase activity (SOD) and glutathione (GSH) content in cells. The JC-1 fluorescent staining observed the effect of DNLA on the mitochondrial membrane potential (MMP) with inverted immunofluorescence microscopy. Western blot was used to detect the levels of mitochondrial apoptosis pathway-related protein and its major downstream proteins Bax, Bcl-2, cleaved-caspase-9, and cleaved-caspase-3. Results. DNLA can significantly improve the viability and apoptosis rate of PC12 cell damage induced by Aβ25-35. It also can restore the reduced intracellular ROS content and MMP, while SOD activity and GSH content increase significantly. The expression of apoptosis-related protein Bax, cleaved-caspase-9, and cleaved-caspase-3 decreased when the Bcl-2 protein expression was significantly increased. Conclusion. These findings suggest that it can significantly inhibit the apoptosis of PC12 cell damage induced by Aβ25-35. The mechanism may reduce the level of cellular oxidative stress and thus inhibit the mitochondrial-mediated 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.

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