scholarly journals Regulation of Apelin-13 on Bcl-2 and Caspase-3 and Its Effects on Adipocyte Apoptosis

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Zhan Li ◽  
Sha Wang ◽  
Yiwei He ◽  
Qiong Li ◽  
Guoying Gao ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
Caspase 3 ◽  
Animal Experiments ◽  
Third Generation ◽  
Fat Cell ◽  
Biochemical Indicators ◽  
The Third ◽  
Doi Model ◽  
Antiobesity Drugs

Objective. The effects of apelin-13 on the expression of Bcl-2 and caspase-3 factors and the apoptosis of adipocytes were studied at the cellular and animal levels. Methods. 3T3-L1 preadipocytes were cultured and grouped. The third-generation cells were added to the control DMSO solvent and amidation-modified apelin-13. The expression of Bcl-2 and caspase-3 were detected. The cell growth viability and cell apoptosis were detected. DOI model rats were established. The effects of apelin-13 on DOI rat biochemical indicators, the expression of Bcl-2, caspase-3, and cell apoptosis were investigated by injecting amidation-modified apelin-13 through the tail vein. Result. In in vitro experiments, amidation-modified apelin-13 can significantly reduce the growth viability of adipocytes and the expression of Bcl-2, increase the expression of caspase-3, and promote the apoptosis of adipocytes. Animal experiments also show that apelin-13 modified by amidation can adjust the abnormal biochemical indicators of DOI rats, decrease the expression of Bcl-2 in adipose tissue, increase the expression of caspase-3, and promote the apoptosis of adipocytes. Conclusion. Amidation of apelin-13 can promote fat cell apoptosis and reduce the incidence of obesity. The mechanism may be accomplished by inhibiting Bcl-2 and caspase-3 factors. This study helps us understand the effect of apelin-13 on fat cell apoptosis and hopes to provide a basis for the development of antiobesity drugs.

scholarly journals Haloperidol and Risperidone Induce Apoptosis Neuronal Cell : Invivo Study

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Ester G Panserga ◽  
Cecep S Kristanto ◽  
Budi Pratiti ◽  
Patricia Wulandari
Keyword(s):  
Cell Apoptosis ◽  
Wistar Rats ◽  
Caspase 3 ◽  
Neuronal Cells ◽  
Neuronal Cell ◽  
Total Percentage ◽  
White Rats ◽  
Male Wistar Rats ◽  
Group B

Abstract Introduction Antipsychotics are drugs that are widely prescribed for mental disorders, such as schizophrenia and psychosis. Recent in vitro studies show antipsychotics play a role in the initiation of neuronal cell apoptosis. This study aims to determine the effect of haloperidol and risperidone on neuronal cell apoptosis in Wistar white rats. Methods Male wistar rats aged 8 weeks (n = 30) were used in this study. Wistar rats were randomized into 6 groups. Group A: 5 wistar rats as a control without induced schizophrenia, aquades and drugs. Group B: 5 Wistar-induced psychotic mice (using 30 mg / kgBB ketamine, intraperitoneal injection for 5 days) and aquadest. Group C: 5 rats were induced psychotic and were given haloperidol or 0.05 mg / kgBB orally, for 28 days. Group D: 5 mice were induced psychotic and were given haloperidol 0.1 mg / kg orally, for 28 days. Group E: 5 mice were induced psychotic and were given risperidone 0.05 mg / kgBB orally, for 28 days. Group F: 5 mice were induced psychotic and given risperidone 0.1 mg / kgBB orally, for 28 days. Apoptosis of neuronal cells in the ventral tegmental area was assessed by caspase-3 immunohistochemistry. The colored area will be calculated as a total percentage using the imageJ program. Results Risperidone and haloperidol increase caspase-3 activity, but haloperidol increases caspase-3 activity more than risperidone. Conclussion Risperidone and haloperidol induce apoptosis of neuronal cells and tardive dyskinesia in Wistar rats with psychotic models.

Beauvericin Inhibits the Growth of U251 Glioma Cells and Promotes Apoptosis In Vitro

2020 ◽  
Vol 14 (5) ◽  
pp. 639-644
Author(s):  
Liming Hu ◽  
Tianyi Zhao ◽  
Jia Wang ◽  
Renguang Wang ◽  
Hongshi Bu ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Glioma Cells ◽  
Inhibitory Effect ◽  
U251 Cell ◽  
Western Blot Assay ◽  
Expression Levels ◽  
Signal Transduction Proteins

To elucidated the inhibitory effect of beauvericin (BEA) on glioma cells and its possible molecular mechanism, in this study, the MTT assay was performed to observed the effect of BEA on cell proliferation, the flow cytometry was used to measure its protective effect on cell apoptosis, and the Western Blot assay was performed to test the expression levels of signal transduction proteins. In the results, the concentration of BEA was 0.5 μmoL/L in the drug group, indicating that it has obvious protect effect to the U251 cells. The apoptosis rates of BEA, Cis and BEA+Cis groups, compared with the U251 group, were 2.93, 3.71 and 5.0 times higher respectively. In addition, the expression levels of Cyclin D1, E, B and Bcl-2 in BEA group were 75, 69, 78 and 67% of that in the U251 group, while Bax and cleaved caspase-3 were twice as much as that in the U251 group. In conclusion, beauvericin can inhibit U251 cell apoptosis and the possible mechanism is to reduce the expression of Cyclin D1, B, E and Bcl-2, while the levels of Bax and cleaved Caspase-3 increased. Thus, BEA has a broad application prospect in the treatment of glioma.

scholarly journals Mechanism of action of the third generation benzopyrans and evaluation of their broad anti-cancer activity in vitro and in vivo

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Alexander J. Stevenson ◽  
Eleanor I. Ager ◽  
Martina A. Proctor ◽  
Dubravka Škalamera ◽  
Andrew Heaton ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Third Generation ◽  
The Third ◽  
Anti Cancer ◽  
Cancer Activity

scholarly journals Relaxin Attenuates Contrast-Induced Human Proximal Tubular Epithelial Cell Apoptosis by Activation of the PI3K/Akt Signaling Pathway In Vitro

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Xiang-Cheng Xie ◽  
Yizhi Cao ◽  
Xiu Yang ◽  
Qun-Hong Xu ◽  
Wei Wei ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Kidney Injury ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Bax Protein ◽  
Phosphorylated Akt

Background. Contrast-induced acute kidney injury (CI-AKI) is one of the main causes of iatrogenic acute kidney injury (AKI); however, therapeutic strategies for AKI remain limited. This study aims to explore the effect of relaxin (RLX) on contrast-induced HK-2 apoptosis and its underlying mechanisms.Methods. Renal tubular epithelial cells (HK-2) were incubated either with or without ioversol, human H2 relaxin, and LY294002 (the inhibitor of the PI3K/Akt signal pathway). Cell viability was evaluated with a CCK-8 assay. Apoptotic morphologic alterations were observed using the Hoechst 33342 staining method. Apoptosis was detected with Annexin V staining. Western blot analysis was employed to measure the expression of pAkt (S473), Akt, cleaved caspase-3, Bcl-2, Bax, and actin proteins.Results. Ioversol reduced the viability of HK-2 cells. Western blotting results revealed decreased expression of phosphorylated Akt in cells treated with ioversol. The activities of caspase-3 and Bax protein increased, while the expression of Bcl-2 protein decreased. As a result, the Bax/Bcl-2 ratio increased after treatment with ioversol. These effects were reversed when HK-2 cells were cotreated with RLX. However, with preadministration of PI3K/Akt pathway inhibitor LY294002, the effect of RLX was blocked.Conclusion. Our study demonstrates that relaxin attenuates ioversol induced cell apoptosis via activation of the PI3K/Akt signaling pathway, suggesting that RLX might play a protective role in the treatment of CI-AKI.

scholarly journals Toxicity Effects of Methylene Blue on Rat Intervertebral Disc Annulus Fibrosus Cells

2019 ◽  
Vol 2 (22.2) ◽  
pp. 155-164
Author(s):  
Liang Zhang
Keyword(s):  
Methylene Blue ◽  
Cell Apoptosis ◽  
Annulus Fibrosus ◽  
Caspase 3 ◽  
In Vitro Study ◽  
Collagen Type I ◽  
Type I ◽  
Dependent Manner ◽  
Concentration Dependent Manner

Background: There is an increasing local application of methylene blue (MB) in the treatment of discogenic low back pain (LBP) and percutaneous transforaminal endoscopic discectomy (PTED) procedures. MB could generate DNA damage and induce apoptosis in different cell types; however, the effects of MB on intervertebral disc (IVD) annulus fibrosus (AF) cells are not clearly understood. Objective: The objective of this study was to investigate the effects of different concentrations of MB on rat AF cells in vitro. Study Design: This study used an experimental design. Setting: This research was conducted at the Orthopaedic Institute of the Clinical Medical College of Yangzhou University. Methods: AF cells were isolated and cultured with different concentrations of MB (0, 2, 20, and 200 μg/mL) and assessed to determine the possible cytotoxic effects of MB. The cell proliferation was detected by Cell Counting Kit-8 (CCK-8) assay. The inverted phase-contrast microscopy was used to perform morphological observation of apoptotic cells, and flow cytometry was used to measure the incidence of cell apoptosis. The mRNA and protein expression levels of apoptosis-associated genes (caspase-3, Bcl-2, and Bax) and other related genes (collagen type I, transforming growth factor β1 [TGF-β1], fibroblast growth factor [bFGF], and tissue inhibitor of metalloproteinase-1 [TIMP-1]) were analyzed by quantitative real-time PCR (RT-PCR) and Western blotting. Results: Our results indicated that MB reduced cell viability in a concentration- and timedependent manner. MB also induced marked AF cell apoptosis in a concentration-dependent manner observed by inverted phase-contrast microscopy, flow cytometry, and indicated by the increased expression of caspase-3. Both RT-PCR and Western blotting revealed significant upregulation of Bax and caspase-3 expression levels accompanied by decreased expression of Bcl2 in a concentration-dependent manner. Moreover, collagen type I, TGF-β1, bFGF, and TIMP-1 mRNA and protein levels were also found to be decreased by MB in a concentration-dependent manner. Limitations: Limitations of this study were the in vitro study design and lack of in vivo validation of the observed effects of MB on human IVD cells. Conclusions: Our results indicate that a high concentration of MB can not only inhibit proliferation and paracrine function of AF cells, but can also induce cell apoptosis in a concentration-dependent manner, suggesting that it is necessary to choose low concentrations of MB in practical application and limit the use of MB in the treatment of discogenic LBP to research protocols. Key words: Methylene blue, annulus fibrosus cell, proliferation, apoptosis, paracrine

scholarly journals ANTIPSYCHOTICS: FROM THE FIRST TO THE THIRD GENERATION

2020 ◽  
Author(s):  
Nataliia N. Petrova ◽  
Alexander G. Sofronov
Keyword(s):  
Comparative Analysis ◽  
Negative Symptoms ◽  
Third Generation ◽  
Antipsychotic Therapy ◽  
Persistent Symptoms ◽  
D3 Receptors ◽  
The Third ◽  
Personalized Approach

The review is devoted to comparative analysis of antipsychotics of three generations. When writing the review, a systematic search in the databases PubMed, Medline, Elsevier was carried out, a simple filter for keywords was used. Pharmacological and clinical issues of antipsychotic therapy were considered, the mechanisms of action of antipsychotics of different generations were revealed. Current trends in the development of approaches to the therapy of schizophrenia and the concept of atypicality of antipsychotics were discussed. A comparative analysis of indications for use, tolerance (safety of use) and efficacy of various antipsychotic drugs with an emphasis on the effect on negative (primary, persistent) symptoms has been conducted. The hypothesis underlying new approaches to the therapy of schizophrenia, based on the effect on dopamine autoreceptors, consisting of a high density of D2 and low density of D3 receptors, has been presented. It has been shown that antipsychotics of the third generation open up new possibilities in the therapy of psychosis within the framework of a personalized approach in psychiatry with the achievement of functional recovery of patients. The characteristics of the drugs representatives of the third generation of antipsychotics aripiprazole and cariprazine were given. The uniqueness of cariprazine as the only drug that inhibits D3 receptors in vitro, as well as in vivo in patients with schizophrenia was emphasized. The data of evidence-based studies of the effectiveness of cariprazine in the treatment of negative, including predominant negative symptoms were presented.

scholarly journals Responses of apoptosis and matrix metabolism of annulus fibrosus cells to different magnitudes of mechanical tension in vitro

2019 ◽  
Vol 39 (2) ◽  
Author(s):  
Yanhai Jiang ◽  
Lianqiang Fu ◽  
Yeliang Song
Keyword(s):  
Protein Expression ◽  
Cell Apoptosis ◽  
Annulus Fibrosus ◽  
Caspase 3 ◽  
Mechanical Load ◽  
Control Group ◽  
Mechanical Tension ◽  
Matrix Metabolism ◽  
Apoptosis Ratio

Abstract Background: Annulus fibrosus (AF) is important to confine disc nucleus pulposus (NP) tissue during mechanical load experience. However, the knowledge on AF cell biology under mechanical load is much limited compared with disc NP. Objective: The present study aimed to investigate responses of apoptosis and matrix metabolism of AF cells to different magnitudes of mechanical tension in vitro. Methods: Rat AF cells were subjected to different magnitudes (5, 10, and 20% elongations at a frequency of 1.0 Hz for 6 h per day) of mechanical tension for 7 days. Control AF cells were cultured without mechanical tension. Cell apoptosis ratio, caspase-3 activity, gene/protein expression of apoptosis-related molecules (Bcl-2, Bax, caspase-3/cleaved caspase-3 and cleaved PARP), matrix macromolecules (aggrecan and collagen I) and matrix metabolism-related enzymes (TIMP-1, TIMP-3, MMP-3, and ADAMTS-4) were analyzed. Results: Compared with 5% tension group and control group, 10 and 20% tension groups significantly increased apoptosis ratio, caspase-3 activity, up-regulated gene/protein expression of Bax, caspase-3/cleaved caspase-3, cleaved PARP, MMP-3, and ADAMTS-4, whereas down-regulated gene/protein expression of Bcl-2, aggrecan, collagen I, TIMP-1, and TIMP-3. No significant difference was found in these parameters apart from Bcl-2 expression between the control group and 5% tension group. Conclusion: High mechanical tension promotes AF cell apoptosis and suppresses AF matrix synthesis compared with low mechanical tension. The present study indirectly indicates how mechanical overload induces disc degeneration through affecting AF biology.

scholarly journals 12-Epi-Napelline Inhibits Leukemia Cell Proliferation via the PI3K/AKT Signaling Pathway In Vitro and In Vivo

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Jia Han ◽  
Wei Hou ◽  
Bi-qing Cai ◽  
Fan Zhang ◽  
Jian-cai Tang
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Caspase 3 ◽  
Animal Experiments ◽  
Leukemia Cell ◽  
Tumor Model ◽  
Inhibitory Effect ◽  
Induced Apoptosis

This study aimed to investigate the inhibitory effect of 12-epi-napelline on leukemia cells and its possible mechanisms. The inhibitory effects of 12-epi-napelline on K-562 and HL-60 cells were evaluated using the CCK-8 assay, cell cycle arrest and apoptosis were detected by flow cytometry, and the expression of related proteins was measured by western blot. A K-562 tumor model was established to evaluate the antitumor effect of 12-epi-napelline in vivo. A reduction in leukemia cell viability was observed after treatment with 12-epi-napelline. It was determined that the cell cycle was arrested in the G0/G1 phase, and the cell apoptosis rate was increased. Moreover, caspase-3 and Bcl-2 were downregulated, whereas cleaved caspase-3 and caspase-9 were upregulated. Further study revealed that 12-epi-napelline could suppress the expression of PI3K, AKT, p-AKT, and mTOR. Insulin-like growth factor 1 (IGF-1) attenuated 12-epi-napelline-induced apoptosis and ameliorated the repression of PI3K, AKT, p-AKT, and mTOR by 12-epi-napelline. Animal experiments clearly showed that 12-epi-napelline inhibited tumor growth. In conclusion, 12-epi-napelline restrained leukemia cell proliferation by suppressing the PI3K/AKT/mTOR pathway in vitro and in vivo.

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