Inactivation of PI3k/Akt signaling pathway and activation of caspase-3 are involved in tanshinone I-induced apoptosis in myeloid leukemia cells in vitro

2010 ◽  
Vol 89 (11) ◽  
pp. 1089-1097 ◽  
Author(s):  
Jia-Jun Liu ◽  
Wen-Da Liu ◽  
Hong-Zhi Yang ◽  
Yong Zhang ◽  
Zhi-Gang Fang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Myeloid Leukemia ◽  
Caspase 3 ◽  
Akt Signaling ◽  
Leukemia Cells ◽  
Akt Signaling Pathway ◽  
Tanshinone I ◽  
Induced Apoptosis

scholarly journals Adiponectin Attenuates Lipopolysaccharide-induced Apoptosis by Regulating the Cx43/PI3K/AKT Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Luqian Liu ◽  
Meijuan Yan ◽  
Rui Yang ◽  
Xuqing Qin ◽  
Ling Chen ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Akt Signaling ◽  
Myocardial Tissue ◽  
H9c2 Cells ◽  
Akt Signaling Pathway ◽  
Cx43 Expression ◽  
Induced Apoptosis

Cardiomyocyte apoptosis is a crucial factor leading to myocardial dysfunction. Adiponectin (APN) has a cardiomyocyte-protective impact. Studies have shown that the connexin43 (Cx43) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathways play an important role in the heart, but whether APN plays a protective role by regulating these pathways is unclear. Our study aimed to confirm whether APN protects against lipopolysaccharide (LPS)-induced cardiomyocyte apoptosis and to explore whether it plays an important role through regulating the Cx43 and PI3K/AKT signaling pathways. In addition, our research aimed to explore the relationship between the Cx43 and PI3K/AKT signaling pathways. In vitro experiments: Before H9c2 cells were treated with LPS for 24 h, they were pre-treated with APN for 2 h. The cytotoxic effect of APN on H9c2 cells was evaluated by a CCK-8 assay. The protein levels of Bax, Bcl2, cleaved caspase-3, cleaved caspase-9, Cx43, PI3K, p-PI3K, AKT and p-AKT were evaluated by Western blot analysis, and the apoptosis rate was evaluated by flow cytometry. APN attenuated the cytotoxicity induced by LPS. LPS upregulated Bax, cleaved caspase-3 and cleaved caspase-9 and downregulated Bcl2 in H9c2 cells; however, these effects were attenuated by APN. In addition, LPS upregulated Cx43 expression, and APN downregulated Cx43 expression and activated the PI3K/AKT signaling pathway. LPS induced apoptosis and inhibited PI3K/AKT signaling pathway in H9c2 cells, and these effects were attenuated by Gap26 (a Cx43 inhibitor). Moreover, the preservation of APN expression was reversed by LY294002 (a PI3K/AKT signaling pathway inhibitor). In vivo experiments: In C57BL/6J mice, a sepsis model was established by intraperitoneal injection of LPS, and APN was injected into enterocoelia. The protein levels of Bax, Bcl2, cleaved caspase-3, and Cx43 were evaluated by Western blot analysis, and immunohistochemistry was used to detect Cx43 expression and localization in myocardial tissue. LPS upregulated Bax and cleaved caspase-3 and downregulated Bcl2 in sepsis; however, these effects were attenuated by APN. In addition, the expression of Cx43 was upregulated in septic myocardial tissue, and APN downregulated Cx43 expression in septic myocardial tissue. In conclusion, both in vitro and in vivo, the data demonstrated that APN can protect against LPS-induced apoptosis during sepsis by modifying the Cx43 and PI3K/AKT signaling pathways.

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 Growth hormone activates PI3K/Akt signaling and inhibits ROS accumulation and apoptosis in granulosa cells of patients with polycystic ovary syndrome

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Yan Gong ◽  
Shan Luo ◽  
Ping Fan ◽  
Huili Zhu ◽  
Yujing Li ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Polycystic Ovary ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Caspase 9 ◽  
Ovary Syndrome ◽  
Gh Treatment ◽  
Induced Apoptosis

Abstract Background It is reported that growth hormone (GH) can alleviate oxidative stress (OS) induced apoptosis in some types of cells by activating the PI3K/Akt signaling pathway. This study investigated the role and underlying mechanism of GH in OS and apoptosis in granulosa cells (GCs) of patients with polycystic ovary syndrome (PCOS). Methods Primary GCs were collected from patients with and without PCOS (controls, n = 32) during oocyte retrieval. The patients with PCOS were randomly assigned to take GH treatment (PCOS-GH, n = 30) or without GH treatment (PCOS-C, n = 31). Reactive oxygen species (ROS) level was determined by spectrophotometry and fluorescence microscopy. GC apoptosis and mitochondrial membrane potential (MMP) were detected by Annexin V-FITC/PI double-staining and JC-1 staining, respectively (flow cytometry). The expression of apoptosis-related genes and proteins involved in PI3K/Akt signaling was determined by quantitative reverse-transcription polymerase chain reaction and western blotting, while active caspase-9 and caspase-3 levels of GCs were determined by enzyme-linked immunosorbent assay. Results Our study found that in GCs of the PCOS-GH group, the ROS levels and apoptotic rates were significantly decreased, whereas MMP was significantly increased when compared to those in the PCOS-C group (P < 0.05). The mRNA levels of FOXO1, Bax, caspase-9, and caspase-3 were significantly decreased, whereas Bcl-2 was increased in GCs of the PCOS-GH group than those in the PCOS-C group (P < 0.05). The protein levels of FOXO1, Bax, cleaved caspase-9/caspase-9 and cleaved caspase-3/caspase-3 were decreased, whereas p-PI3K/PI3K, p-Akt/Akt, p-FOXO1 and Bcl-2 were increased in GCs of the PCOS-GH group, compared with those in the PCOS-C group (P < 0.05). Conclusion OS induced apoptosis and downregulated the PI3K/Akt signaling pathway in patients with PCOS. GH could alleviate apoptosis and activate the PI3K/Akt signaling pathway. Clinical trial registration number Chinese Clinical Trial Registry. ChiCTR1800019437. Prospectively registered on October 20, 2018.

In Vitro Effects of Propofol on Cytotoxic, Apoptotic and PI3K-Akt Signaling Pathway Genes on Brain Cancer Cells

2021 ◽  
Vol 21 ◽  
Author(s):  
Tuba Gokdogan Edgunlu ◽  
Cigir Biray Avci ◽  
Neslihan Pınar Ozates ◽  
Bakiye Goker Bagca ◽  
Sevim Karakas Celik ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Glioma Cells ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Expression Levels ◽  
Proliferation And Apoptosis ◽  
Apoptotic Effect ◽  
In Vitro Effects ◽  
Induced Apoptosis

Aim: It was aimed to determine the cytotoxic and apoptotic effect of propofol on glioma cells. Background: Propofol [2,6-diisopropylphenol] is a commonly used intravenous anesthetic. Propofol is known to have a mechanism of action on the PI3K-AKT pathway. Objective: This study aimed to evaluate the effect of propofol on the proliferation and apoptosis of human glioma cells, as well as to investigate changes in expression levels of the PI3K-AKT signaling pathway genes. Results: We have shown that propofol-induced apoptosis in U-87 MG cells by 17.1-fold compared to untreated control. Furthermore, significant differences were found in the expression levels of the PI3K-AKT signaling pathway genes. Conclusion: As a result of our study, it was found that propofol caused differences in expression levels of PI3K-AKT signaling pathway genes, and it was suggested that these differences might be related to apoptosis induction.

scholarly journals Irisin Protects the Human Placenta from Oxidative Stress and Apoptosis via Activation of the Akt Signaling Pathway

2021 ◽  
Vol 22 (20) ◽  
pp. 11229
Author(s):  
Hamid-Reza Kohan-Ghadr ◽  
Brooke Armistead ◽  
Mikaela Berg ◽  
Sascha Drewlo
Keyword(s):  
Signaling Pathway ◽  
Human Placenta ◽  
Ex Vivo ◽  
Akt Signaling ◽  
In Vitro Models ◽  
Akt Signaling Pathway ◽  
Placental Development ◽  
Vitro Model ◽  
Induced Apoptosis

Irisin is a newly discovered exercise-mediated polypeptide hormone. Irisin levels increase during pregnancy however, women with preeclampsia (PE) have significantly lower levels of Irisin compared to women of healthy pregnancies. Even though many studies suggest a role of Irisin in pregnancy, its function in the human placenta is unclear. In the current study, we aimed to understand key roles of Irisin through its ability to protect against apoptosis is the preeclamptic placenta and in ex vivo and in vitro models of hypoxia/re-oxygenation (H/R) injury. Our studies show that Irisin prevents cell death by reducing pro-apoptotic signaling cascades, reducing cleavage of PARP to induce DNA repair pathways and reducing activity of Caspase 3. Irisin caused an increase in the levels of anti-apoptotic BCL2 to pro-apoptotic BAX and reduced ROS levels in an in vitro model of placental ischemia. Furthermore, we show that Irisin treatment acts through the Akt signaling pathway to prevent apoptosis and enhance cell survival. Our findings provide a novel understanding for the anti-apoptotic and pro-survival properties of Irisin in the human placenta under pathological conditions. This work yields new insights into placental development and disease and points towards intervention strategies for placental insufficiencies, such as PE, by protecting and maintaining placental function through inhibiting hypoxic ischemia-induced apoptosis.

scholarly journals Growth Hormone Activates PI3K/Akt Signaling and Inhibits ROS Accumulation and Apoptosis in Granulosa Cells of Patients With Polycystic Ovary Syndrome

2020 ◽  
Author(s):  
Yan Gong ◽  
Shan Luo ◽  
Ping Fan ◽  
Huili Zhu ◽  
Yujing Li ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Growth Hormone ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Polycystic Ovary ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Caspase 9 ◽  
Ovary Syndrome ◽  
Induced Apoptosis

Abstract Background: Growth hormone (GH) can reduce oxidative stress (OS) induced apoptosis in some types of cells by activating the PI3K/Akt signaling pathway. This study investigated the role and underlying mechanism of GH in OS and apoptosis in GCs of patients with polycystic ovary syndrome (PCOS). Methods: Primary GCs were collected from patients with and without PCOS (controls, n = 32) during oocyte retrieval. The patients with PCOS were randomly assigned to receive treatment with GH (PCOS-GH, n = 30) or without GH (PCOS-C, n = 31). Reactive oxygen species (ROS) level was determined by spectrophotometry and fluorescence microscopy. GC apoptosis and mitochondrial membrane potential (MMP) were detected by Annexin V-FITC/PI double-staining and JC-1 staining, respectively (flow cytometry). The expression of apoptosis-related genes and proteins involved in PI3K/Akt signaling was determined by quantitative reverse-transcription polymerase chain reaction and western blotting, while active caspase-9 and caspase-3 levels were determined by enzyme-linked immunosorbent assay. Result(s): The present study found that compared with those in the non-PCOS and PCOS-GH groups, the ROS levels and apoptotic rates were significantly increased, whereas MMP was significantly decreased in the PCOS-C group GCs (P < 0.05). Compared with those in non-PCOS and PCOS-GH groups, mRNA levels of FOXO1, Bax, caspase-9, and caspase-3 were significantly increased, whereas Bcl-2 was decreased in the GCs of the PCOS-C group (P < 0.05). The protein levels of FOXO1, Bax, cleaved caspase-9/caspase-9 and cleaved caspase-3/caspase-3 were increased, whereas p-PI3K/PI3K, p-Akt/Akt, p-FOXO1 and Bcl-2 were decreased in the GCs of the PCOS-C group, compared with those in the non-PCOS and PCOS-GH groups (P < 0.05). Conclusion: OS induced apoptosis and inactivated the PI3K/Akt signaling pathway in patients with PCOS. GH could improve apoptosis and activate the PI3K/Akt signaling pathway.Clinical Trial Registration Number: Chinese Clinical Trial Registry (www.chictr.org.cn/index.aspx). ChiCTR1800019437. Prospectively registered on October 20, 2018, http://www.chictr.org.cn/edit.aspx?pid=28663&htm= 4

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