scholarly journals Xuan Bi Tong Yu Fang Promotes Angiogenesis via VEGF-Notch1/Dll4 Pathway in Myocardial Ischemic Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Shuangdi Li ◽  
Jingrong Dong ◽  
Guang Ta ◽  
Yinghui Liu ◽  
Junfeng Cui ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
Caspase 3 ◽  
Tunel Staining ◽  
Sprague Dawley ◽  
Caspase 9 ◽  
Mitochondrial Structure ◽  
Transmission Electron ◽  
Sprague Dawley Rats ◽  
Cyt C ◽  
Endothelial Growth Factor

Objective. To investigate the effect of Xuan Bi Tong Yu Fang (XBTYF) on angiogenesis via the vascular endothelial growth factor- (VEGF-) Notch1/delta-like 4 (Dll4) pathway. Materials and Methods. Sixty Sprague-Dawley rats were randomly divided into six groups: control, sham-operated, myocardial ischemia model, and XBTYF treatment at 3.2, 1.6, and 0.8 g/kg. Electrocardiography was performed to evaluate the successful establishment of the model. Hematoxylin-eosin staining and transmission electron microscopy were carried out to observe the morphology and mitochondrial structure in myocardial cells, respectively. TUNEL staining was performed to assess the degree of cell apoptosis. The expression of VEGF-A, Notch1, Dll4, Bcl2, Bax, caspase 3, caspase 9, and cytochrome-c (Cyt-c) was observed by western blot. Results. XBTYF inhibited changes to the morphology and mitochondrial structure in cardiomyocyte and reduced cell apoptosis. Compared with the model group, XBTYF at all doses (3.2, 1.6, and 0.8 g/kg) reduced the expression of Notch1, Dll4, Bax, caspase 3, caspase 9, and Cyt-c, whereas expression of VEGF-A and Bcl2 was increased. Conclusion. XBTYF attenuated mitochondrial damage and cell apoptosis while promoting the angiogenesis of cardiomyocyte. The associated mechanism may be related to the VEGF-Notch1/Dll4 pathway.

scholarly journals Mechanism of Heshouwuyin inhibiting the Cyt c/Apaf-1/Caspase-9/Caspase-3 pathway in spermatogenic cell apoptosis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hongjie Wang ◽  
Juan Zhu ◽  
Liping Jiang ◽  
Boying Shan ◽  
Peihan Xiao ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
Caspase 3 ◽  
Spermatogenic Cell ◽  
Caspase 9 ◽  
Cyt C

Overexpression of miR-146a inhibits the apoptosis of hippocampal neurons of rats with cerebral hemorrhage by regulating autophagy

2020 ◽  
Vol 39 (9) ◽  
pp. 1178-1189
Author(s):  
S Huan ◽  
J Jin ◽  
C-x Shi ◽  
T Li ◽  
Z Dai ◽  
...  
Keyword(s):  
Western Blot ◽  
Hippocampal Neurons ◽  
Caspase 3 ◽  
Nuclear Factor Κb ◽  
Beclin 1 ◽  
Sprague Dawley ◽  
Related Factors ◽  
Expression Levels ◽  
Transmission Electron ◽  
Sprague Dawley Rats

In this study, to investigate the effect of overexpression of miR-146a on autophagy of hippocampal neurons in rats with intracerebral hemorrhage (ICH), 72 Sprague-Dawley rats were randomly divided into the sham, ICH, miR-146a agomir, and miR-146a agomir control groups. The ICH model was constructed by injection of collagenase VII. The apoptosis of hippocampal neurons was measured by TUNEL assay. The levels of LC3 and Beclin 1 were analyzed by immunohistochemistry. Mitochondrial autophagy was examined by transmission electron microscopy. The levels of LC3A, LC3B, Beclin 1, Bax, Bcl-2, and cleaved caspase 3 were examined by Western blot. Western blot was also used to evaluate the expression of nuclear factor κB signaling pathway-related factors. To examine the effect of autophagy inhibitor (3-methyladenine (3-MA)) on miR-146a-regulated apoptotic protein expression, 30 rats were further divided into the sham, ICH, miR-146a agomir, 3-MA, and miR-146a + 3-MA groups. The levels of Bax, Bcl-2, and cleaved caspase 3 were examined by Western blot. Compared with the sham group, the nerve function scores, brain water content, the percentage of apoptotic cells, and the expression levels of LC3, Beclin 1, Bax, cleaved caspase 3, and p-P65 in the hippocampus of rats in the ICH group were all significantly increased ( p < 0.05), whereas the expression levels of miR-146a, Bcl-2, and p-IκBα were markedly decreased ( p < 0.05). Mitochondrial autophagy was also evident. Furthermore, compared with the ICH group, the results of the abovementioned tests in the miR-146a agomir group were reversed. The overexpression of miR-146a inhibited the autophagy of hippocampal neurons in rats with ICH.

Liver Toxicity in Rats Fed A Mixture of Pcb Congeners and 2,3,7,8-Tcdd

1997 ◽  
Vol 3 (S2) ◽  
pp. 51-52
Author(s):  
B.J. Cornell ◽  
A. Singh ◽  
I. Chu
Keyword(s):  
Aromatic Compounds ◽  
Liver Toxicity ◽  
Corn Oil ◽  
Morphological Changes ◽  
Test Substance ◽  
Sprague Dawley ◽  
Morphological Alterations ◽  
Pcb Congeners ◽  
Transmission Electron ◽  
Sprague Dawley Rats

Polyhalogenated aromatic compounds such as polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins (PCDDs) continue to be environmental contaminants because of their bioaccumulation in the food chain and high resistance to biodegradation. The current study was undertaken to determine if a mixture of PCB congeners (WHO-IPCS) were interactive with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in producing morphological changes in the rat liver. Both compounds are known to produce a broad range of biochemical and morphological alterations including enzyme induction.Groups (N=5) of female Sprague-Dawley rats were administered TCDD (0, 2.5, 25, 250, 1000 ng/kg bw/day) or PCB (0, 2, 20 μg/kg bw/day) alone, or in combination with each concentration of both compounds. Incorrect concentrations were published in a previous abstract. The test substance was mixed with corn oil and given by gavage at 2 ml/kg daily for 28 days. At the end of the experiment, the rats were killed and liver samples were prepared for transmission electron microscopy.

DNA damage-induced neural precursor cell apoptosis requires p53 and caspase 9 but neither Bax nor caspase 3

Development ◽  
2001 ◽  
Vol 128 (1) ◽  
pp. 137-146
Author(s):  
C. D'Sa-Eipper ◽  
J.R. Leonard ◽  
G. Putcha ◽  
T.S. Zheng ◽  
R.A. Flavell ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Cell Apoptosis ◽  
Neuronal Apoptosis ◽  
Caspase 3 ◽  
Precursor Cell ◽  
Neural Precursor ◽  
Normal Brain ◽  
Neural Precursor Cell ◽  
Caspase 9

Programmed cell death (apoptosis) is critical for normal brain morphogenesis and may be triggered by neurotrophic factor deprivation or irreparable DNA damage. Members of the Bcl2 and caspase families regulate neuronal responsiveness to trophic factor withdrawal; however, their involvement in DNA damage-induced neuronal apoptosis is less clear. To define the molecular pathway regulating DNA damage-induced neural precursor cell apoptosis, we have examined the effects of drug and gamma-irradiation-induced DNA damage on telencephalic neural precursor cells derived from wild-type embryos and mice with targeted disruptions of apoptosis-associated genes. We found that DNA damage-induced neural precursor cell apoptosis, both in vitro and in vivo, was critically dependent on p53 and caspase 9, but neither Bax nor caspase 3 expression. Neural precursor cell apoptosis was also unaffected by targeted disruptions of Bclx and Bcl2, and unlike neurotrophic factor-deprivation-induced neuronal apoptosis, was not associated with a detectable loss of cytochrome c from mitochondria. The apoptotic pathway regulating DNA damage-induced neural precursor cell death is different from that required for normal brain morphogenesis, which involves both caspase 9 and caspase 3 but not p53, indicating that additional apoptotic stimuli regulate neural precursor cell numbers during telencephalic development.

scholarly journals Tubeimoside-1 Protects Against Renal Ischemia Reperfusion Injury In Vivo and In Vitro

2020 ◽  
Vol 15 (12) ◽  
pp. 1934578X2097764
Author(s):  
Xiaoli Yuan ◽  
Jing Wang ◽  
Yun Zhang
Keyword(s):  
Reperfusion Injury ◽  
Cell Apoptosis ◽  
Renal Cell ◽  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Caspase 9 ◽  
Tnf Α ◽  
Renal Ischemia Reperfusion Injury

Renal ischemia reperfusion injury (RIRI) is one of the main causes of acute kidney injury. This study aimed to explore whether tubeimoside-1 (TBMS1) could protect against RIRI. RIRI mice model and hypoxia/reoxygenation (H/R)-induced NRK-52E cells were used in this study. The renal pathology was observed by hematoxylin and eosin staining to calculate the tubular injury score. The levels of serum creatinine and blood urine nitrogen were analyzed by a Hitachi model 7180 automatic analyzer. The expressions of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin 6 (IL-6), Bax, cleaved caspase-3, cleaved caspase-9, total caspase-3, and total caspase-9 in renal tissues and NRK-52E cells were detected by western blot analysis. The levels of TNF-α, IL-1β, and IL-6 in serum and NRK-52E cells were measured by a commercial enzyme-linked immunosorbent assay kit. The renal cell apoptosis in renal tissues was analyzed by TUNEL assay, and NRK-52E cell apoptosis was detected by flow cytometry analysis. CCK-8 assay was used to analyze the viability of NRK-52E cells after the indicated treatment. As a result, the renal tissues that were seriously damaged in mice with RIRI could be alleviated by TBMS1. Therefore, 50 mg/kg TBMS1 was chosen for the animal experiment. Renal cell apoptosis was increased in renal tissues of mice with RIRI. These changes could be partially reversed by TBMS1 treatment. TBMS1 improved the viability, and reduced the inflammation and apoptosis of H/R-induced NRK-52E cells. In conclusion, TBMS1 ameliorates RIRI by promoting viability and suppressing apoptosis and inflammation of renal cells.

TRIAP1 Inhibition Activates the Cytochrome c/Apaf-1/Caspase-9 Signaling Pathway to Enhance Human Ovarian Cancer Sensitivity to Cisplatin

Chemotherapy ◽  
2019 ◽  
Vol 64 (3) ◽  
pp. 119-128 ◽  
Author(s):  
Tian-Mei Zhang
Keyword(s):  
Ovarian Cancer ◽  
Nude Mice ◽  
Cell Apoptosis ◽  
Caspase 9 ◽  
Ovarian Carcinoma Cell Line ◽  
Skov3 Cells ◽  
Cyt C ◽  
Sirna Group

Objective: To investigate whether TRIAP1inhibition affects the ovarian cancer cell resistance to cisplatin (DDP) via the Cyt c/Apaf-1/caspase-9 pathway by in vitro and in vivo experiments. Methods: CCK8 assay was performed to find out how treatment with both TRIAP1 siRNA and DDP affects the cell viability of SKOV3 cells and DDP-resistant human ovarian carcinoma cell line SKOV3/DDP. SKOV3/DDP cells were transfected with control siRNA or TRIAP1 siRNA before 24 h of treatment with DDP (5 μg/mL). Flow cytometry was employed to detect cell apoptosis and Western blot to examine the expressions of Cyt c/Apaf-1/caspase-9 pathway-related proteins. SKOV3/DDP cells transfected with control siRNA or TRIAP1 siRNA were subcutaneously injected into BALB/c-nu/nu nude mice followed by the intraperitoneal injection of DDP (4 mg/kg). Cyt c/Apaf-1/caspase-9 pathway in transplanted tumors was detected by immunohistochemistry. Results: TRIAP1 expression declined in SKOV3 cells when compared with SKOV3/DDP cells. The proliferation rate was lower in SKOV3/DDP cells transfected with TRIAP1 siRNA combined with treatment of DDP (1, 2, 4, 6, 8, 16, 32 μg/mL) than in those transfected with control siRNA. Moreover, the TRIAP1 siRNA group had an increased SKOV3/DDP cell apoptosis rate with the activation of the Cyt c/Apaf-1/caspase-9 pathway. During DDP treatment, nude mice in TRIAP1 siRNA group had slower growth and smaller size of transplanted tumor than those in control siRNA group, with increased expression of Cyt c, Apaf-1, and caspase-9. Conclusion: TRIAP1 inhibition may enhance the sensitivity of SKOV3/DDP cells to cisplatin via activation of the Cyt c/Apaf-1/caspase-9 pathway.

scholarly journals Endoplasmic reticulum stress regulates cell injury in lipopolysaccharide-induced nerve cells

2020 ◽  
Vol 48 (9) ◽  
pp. 030006052094976
Author(s):  
Min Li ◽  
Ying Zhang ◽  
Jixing Wang
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Viability ◽  
Er Stress ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Cell Injury ◽  
Cell Counting ◽  
Tunel Staining ◽  
Dependent Manner ◽  
Stress Markers

Objective Sepsis-associated encephalopathy (SAE) is a common complication of sepsis, and excessive endoplasmic reticulum (ER) stress is closely correlated with the cell injury caused by sepsis. This study aimed to analyze the possible role of ER stress in SAE cell models. Methods PC12 and MES23.5 cells were treated with increasing concentrations of lipopolysaccharides (LPS). The Cell Counting Kit-8 assay was used to detect cell viability and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was performed to assess cell apoptosis. In addition, the protein expression levels of ER stress markers [GRP78, CHOP, inositol-requiring enzyme 1 (IRE1), and PKR-like ER kinase (PERK)] and apoptosis-related proteins (Bax, Bcl-2, caspase-3, and cleaved caspase-3) were analyzed using western blotting. Results LPS treatment activated ER stress markers in both the PC12 and MES23.5 cells. The overexpression of GRP78 significantly reduced cell viability and enhanced cell apoptosis in a time-dependent manner. An ER stress inhibitor, 4-PBA, significantly enhanced cell viability and inhibited the cell apoptosis induced by LPS. Therefore, an enhanced unfolded protein response (UPR) and UPR suppression may regulate cell apoptosis. Conclusions UPR was shown to be involved in regulating LPS-induced neuron injury. UPR could be a potential therapeutic target in SAE.

scholarly journals OS12.5 Small GTPase RHOE/RND3, a new critical regulator of NF-êB signaling in glioblastoma multiforme?

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii23-iii23
Author(s):  
B Liu ◽  
Q Chen
Keyword(s):  
Animal Model ◽  
Glioblastoma Multiforme ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Critical Role ◽  
Small Gtpase ◽  
Luciferase Assay ◽  
Tunel Staining ◽  
Apoptosis Resistance ◽  
Human Gbm

Abstract Background Abnormal activation of NF-κB signaling is a major mechanism of apoptosis resistance in glioblastoma multiforme (GBM). Therefore, better understanding of the regulation of NF-κB signaling has a significant impact for GBM therapy. Here, we uncovered a critical role of the small GTPase RND3 in regulating the p65 subunit of NF-κB and NF-κB signaling in GBM. MATERIALS AND METHODS Human GBM samples, GBM cells and a human orthotopic GBM-xenografted animal model were used. The mechanisms of RND3 in regulation of NF-κB signaling and GBM cell apoptosis were examined by luciferase assay, quantitative PCR, immunostaining, immunoblotting, immunofluorescence, co-immunoprecipitation, TUNEL staining, JC-1 analysis and flow cytometry. RESULTS Overexpression of RND3 led to reduced p65 activity in GBM cultured cells and a GBM animal model, indicating that the NF-κB pathway is negatively regulated by RND3 in GBM. Mechanistically, we found that RND3 bound p65 and promoted p65 ubiquitination, leading to decreased p65 protein levels. Furthermore, RND3 enhanced cleaved-caspase 3 levels and promoted apoptosis in GBM cells, and RND3 expression was positively correlated with cleaved-caspase 3 and IL-8 in human GBM samples. The effect of RND3 on promoting apoptosis disappeared when p65 ubiquitination was blocked by protease inhibitor carfilzomib or upon co-expression of ectopic p65. CONCLUSION RND3 binds p65 protein and promotes its ubiquitination, resulting in reduced p65 protein expression and inhibition of NF-κB signaling to induce GBM cell apoptosis.

scholarly journals Downregulation of Endogenous Hydrogen Sulfide Pathway Is Involved in Mitochondrion-Related Endothelial Cell Apoptosis Induced by High Salt

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Yanfang Zong ◽  
Yaqian Huang ◽  
Siyao Chen ◽  
Mingzhu Zhu ◽  
Qinghua Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Membrane Potential ◽  
Endothelial Cell ◽  
Cell Apoptosis ◽  
Superoxide Anion ◽  
Mitochondrial Membrane ◽  
Caspase 3 ◽  
High Salt ◽  
Caspase 9

Background. The study aimed to investigate whether endogenous H2S pathway was involved in high-salt-stimulated mitochondria-related vascular endothelial cell (VEC) apoptosis.Methods. Cultured human umbilical vein endothelial cells (HUVECs) were used in the study. H2S content in the supernatant was detected. Western blot was used to detect expression of cystathionine gamma-lyase (CSE), cleaved-caspase-3, and mitochondrial and cytosolic cytochrome c (cytc). Fluorescent probes were used to quantitatively detect superoxide anion generation and measure thein situsuperoxide anion generation in HUVEC. Mitochondrial membrane pore opening, mitochondrial membrane potential, and caspase-9 activities were measured. The cell apoptosis was detected by cell death ELISA and TdT-mediated dUTP nick end labeling (TUNEL) methods.Results. High-salt treatment downregulated the endogenous VEC H2S/CSE pathway, in association with increased generation of oxygen free radicals, decreased mitochondrial membrane potential, enhanced the opening of mitochondrial membrane permeability transition pore and leakage of mitochondrial cytc, activated cytoplasmic caspase-9 and caspase-3 and subsequently induced VEC apoptosis. However, supplementation of H2S donor markedly inhibited VEC oxidative stress and mitochondria-related VEC apoptosis induced by high salt.Conclusion. H2S/CSE pathway is an important endogenous defensive system in endothelial cells antagonizing high-salt insult. The protective mechanisms for VEC damage might involve inhibiting oxidative stress and protecting mitochondrial injury.

25-Hydroxycholesterol impairs endothelial function and vasodilation by uncoupling and inhibiting endothelial nitric oxide synthase

2016 ◽  
Vol 311 (4) ◽  
pp. E781-E790 ◽  
Author(s):  
Zhi-Jun Ou ◽  
Jing Chen ◽  
Wei-Ping Dai ◽  
Xiang Liu ◽  
Yin-Ke Yang ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Endothelial Function ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Immunoblot Analysis ◽  
Tube Formation ◽  
Endothelial Cell Proliferation ◽  
No Production ◽  
Endothelial Cell Apoptosis ◽  
Caspase 9

Endothelial dysfunction is a key early step in atherosclerosis. 25-Hydroxycholesterol (25-OHC) is found in atherosclerotic lesions. However, whether 25-OHC promotes atherosclerosis is unclear. Here, we hypothesized that 25-OHC, a proinflammatory lipid, can impair endothelial function, which may play an important role in atherosclerosis. Bovine aortic endothelial cells were incubated with 25-OHC. Endothelial cell proliferation, migration, and tube formation were measured. Nitric oxide (NO) production and superoxide anion generation were determined. The expression and phosphorylation of endothelial NO synthase (eNOS) and Akt as well as the association of eNOS and heat shock protein (HSP)90 were detected by immunoblot analysis and immunoprecipitation. Endothelial cell apoptosis was monitored by TUNEL staining and caspase-3 activity, and expression of Bcl-2, Bax, cleaved caspase-9, and cleaved caspase-3 were detected by immunoblot analysis. Finally, aortic rings from Sprague-Dawley rats were isolated and treated with 25-OHC, and endothelium-dependent vasodilation was evaluated. 25-OHC significantly inhibited endothelial cell proliferation, migration, and tube formation. 25-OHC markedly decreased NO production and increased superoxide anion generation. 25-OHC reduced the phosphorylation of Akt and eNOS and the association of eNOS and HSP90. 25-OHC also enhanced endothelial cell apoptosis by decreasing Bcl-2 expression and increasing cleaved caspase-9 and cleaved caspase-3 expressions as well as caspase-3 activity. 25-OHC impaired endothelium-dependent vasodilation. These data demonstrated that 25-OHC could impair endothelial function by uncoupling and inhibiting eNOS activity as well as by inducing endothelial cell apoptosis. Our findings indicate that 25-OHC may play an important role in regulating atherosclerosis.

Sign in / Sign up

Export Citation Format

Share Document