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#28549090   2017/05/26 Save this To Up

Sigma-1 Receptor Regulates Mitochondrial Function in Glucose- and Oxygen-Deprived Retinal Ganglion Cells.

Understanding the role of mitochondria in retinal ganglion cells (RGCs) is relevant to human disease as studies have shown mitochondrial abnormalities in primary open-angle glaucoma patients. This study seeks to determine the effects of the sigma-1 receptor (σ-1r) and its agonists on mitochondrial function in oxygen- and glucose- deprived (OGD) purified neonatal RGCs.

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#27863638   2016/11/19 Save this To Up

Comparison of the effects of lipoic acid and glutathione against cisplatin-induced ototoxicity in auditory cells.

The aims of this study were to examine lipoic acid (LA)- or glutathione (GSH)-mediated protection against cytotoxicity following cisplatin exposure in HEI-OC1 auditory cells and measure the potential of LA and GSH to scavenge reactive oxygen species (ROS). This study also compares their protective effects and discusses the determination of a preventive or therapeutic dose.

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#27802519   2016/11/01 Save this To Up

Antiapoptotic Effect of Acetylcholine in Fas-Induced Apoptosis in Human Keratocytes.

To investigate the possible antiapoptotic effect of acetylcholine (ACh) in Fas-mediated apoptosis of primary human keratocytes in vitro, and to explore the underlying mechanism.

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#27639718   2016/09/18 Save this To Up

IL-27 suppresses SKOV3 cells proliferation by enhancing STAT3 and inhibiting the Akt signal pathway.

Ovarian cancer continues to be the most lethal gynecologic malignancy worldwide. IL-27 is a novel member of the IL-12 cytokine family. The aim of this study was to investigate the effects of IL-27 on the ovarian cystadenocarcinoma cell line SKOV3 and determine possible mechanisms underlying its effect. We stably transfected an IL-27 plasmid, empty vector, IL-27 shRNA or negative control into SKOV3 cells. Cell proliferative activity was evaluated using a WST-1 cell proliferation assay kit. Cell viability was quantified by measurements of lactate dehydrogenase release. The mRNA levels of nine genes were tested by q-PCR. Western blotting was used to verify apoptosis and signal pathways. We found that the IL-27 plasmid significantly enhanced cytotoxicity and inhibited the proliferation of SKOV3 cells. Caspase-3 protein was augmented by IL-27 plasmid and abated by IL-27 shRNA. The incremental expression of IL-27 activated the STAT3 pathway and attenuated the Akt pathway. The over-expression of IL-27 could significantly upregulate a series of antitumor cytokines including IL-6, IL-12 and interferon-γ and down-regulate protumor factors such as TLR4 and NF-κB1. Our data show that IL-27 has direct antitumor capacity in ovarian cancer cells via enhancing apoptosis by inducing the STAT3 pathway and restraining the Akt pathway. Précis: IL-27 enhanced the cytotoxicity and suppressed the proliferation of ovarian cancer cells by activating STAT3 and inhibiting the Akt signal pathway. IL-27 plays an important role in antitumor activity against epithelial ovarian cancer.

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#27513630   2016/09/16 Save this To Up

Exogenous hydrogen sulfide exerts proliferation, anti-apoptosis, migration effects and accelerates cell cycle progression in multiple myeloma cells via activating the Akt pathway.

Hydrogen sulfide (H2S), regarded as the third gaseous transmitter, mediates and induces various biological effects. The present study investigated the effects of H2S on multiple myeloma cell progression via amplifying the activation of Akt pathway in multiple myeloma cells. The level of H2S produced in multiple myeloma (MM) patients and healthy subjects was measured using enzyme-linked immunosorbent assay (ELISA). MM cells were treated with 500 µmol/l NaHS (a donor of H2S) for 24 h. The expression levels of phosphorylated-Akt (p-Akt), Bcl-2 and caspase-3 were measured by western blot assay. Cell viability was detected by Cell Counting Kit 8 (CCK-8). The cell cycle was analyzed by flow cytometry. Our results show that the concentration of H2S was higher in MM patients and that it increased in parallel with disease progression. Treating MM cells with 500 µmol/l NaHS for 24 h markedly increased the expression level of Bcl-2 and the activation of p-Akt, however, the expression level of caspase-3 was decreased, cell viability was increased, and cell cycle progression was accelerated in MM cells. NaHS also induced migration in MM cells in transwell migration assay. Furthermore, co-treatment of MM cells with 500 µmol/l NaHS and 50 µmol/l LY294002 for 24 h significantly overset these effects. In conclusion, our findings demonstrate that the Akt pathway contributes to NaHS-induced cell proliferation, migration and acceleration of cell cycle progression in MM cells.

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#27460334   2016/08/08 Save this To Up

Amyloid precursor protein cooperates with c-KIT mutation/overexpression to regulate cell apoptosis in AML1-ETO-positive leukemia via the PI3K/AKT signaling pathway.

It has been reported that amyloid precursor protein (APP) promotes cell proliferation and metastasis in various types of solid cancers. In our previous study, we showed that APP is highly expressed and regulates leukemia cell migration in AML1‑ETO-positive (AE) leukemia. Whether APP is involved in the regulation of AE leukemia cell proliferation or apoptosis is unclear. In the present study we focused on the correlation of APP with c-KIT mutation/overexpression and cell proliferation and apoptosis in AE leukemia. APP and c-KIT expression detected by quantitative real-time (qPCR) method, and c-KIT mutations screened using PCR in bone marrow cells from 65 patients with AE leukemia before their first chemotherapy, were simultaneously assessed. Furthermore, the Kasumi-1 cell line was chosen as the cell model, and the APP gene was knocked down using siRNA technology. The correlation of cell cycle distribution and apoptosis and c-Kit expression with APP expression levels, as well as the regulation of the PI3K/AKT signaling pathway by APP were analyzed in the Kasumi-1 cell line. The results showed that peripheral white blood cell counts (P=0.008) and bone marrow cellularity (P=0.031), but not bone marrow blasts, were correlated with APP expression. Moreover, the patients with APP high expression had a significantly higher incidence of c-KIT mutations (P<0.001) and increased levels of c-KIT expression (P=0.001) and poorer disease outcome. In the Kasumi-1 cell line, as compared with the wild-type and negative control cells, cell apoptosis, both early (P<0.001) and late (P<0.001), was significantly increased when the APP gene was knocked down, concomitant with reduced levels of anti-apoptotic protein Bcl-2 and increased levels of caspase-3 and -9, however, no apparent change was observed in the cell cycle distribution (P>0.05). Moreover, the knockdown of APP markedly decreased c-KIT expression at both the transcription (as evidenced by qPCR analysis) and translation (as confirmed by CD117 assay and western blot analysis) levels, as well as p-AKT and its downstream targets including NF-κB, p53 and Bcl-2. In conclusion, APP may cooperate with c-KIT mutation/overexpression in the regulation of cell apoptosis but not proliferation in AE leukemia via the PI3K/AKT signaling pathway.

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#27372651   2016/07/04 Save this To Up

Geniposide Prevents Hypoxia/Reoxygenation-Induced Apoptosis in H9c2 Cells: Improvement of Mitochondrial Dysfunction and Activation of GLP-1R and the PI3K/AKT Signaling Pathway.

Myocardial ischemia/reperfusion injury is a major cause of morbidity and mortality associated with coronary heart disease. Many studies have demonstrated that natural products are promising chemotherapeutic drugs counteracting the loss of cardiomyocytes. Thus, the purpose of the present study was to investigate the effects of geniposide, a traditional Chinese herb extract from Gardenia jasminoides J. Ellis, on cardiomyocyte apoptosis induced by hypoxia/reoxygenation (H/R) in H9c2 cells, and their underlying mechanisms.

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#27120393   2016/06/04 Save this To Up

Pomegranate peel extract polyphenols induced apoptosis in human hepatoma cells by mitochondrial pathway.

This study was aimed to investigate the influence of pomegranate peel polyphenols (PPPs) on the proliferation and apoptosis of HepG2 cells (a kind of human hepatoma cells) and the related mechanism. The inverted fluorescence microscope and the flow cytometer (FCM) were used to test the changes of the cellular morphology, cell cycle, apoptosis, reactive oxygen species (ROS) and mitochondrial transmembrane potential (Δψm). The kit was used to measure the activities of caspase-3/9, and Western Blot was used to detect the expressions of apoptosis-associated proteins including p53, Bcl-2/Bax, Cyt-c and PARP. The results showed that the cells cycle of HepG2 arrested at the S-phase by PPPs and the amount of the early apoptotic cells and ROS level were increased obviously, the level of Cyt-c and the activity of Caspase-3/9 markedly were also increased by PPPs, as well as the ratio of Bax/Bcl-2 and the protein expressions of P53. It was concluded that PPPs could inhibit the growth of HepG2 cells by blocking the cell cycle and inducing the mitochondrial apoptotic pathway in a dose-dependent manner.

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#27108411   2016/04/25 Save this To Up

17β-Estradiol Protects Rat Annulus Fibrosus Cells Against Apoptosis via α1 Integrin-Mediated Adhesion to Type I Collagen: An In-vitro Study.

BACKGROUND 17β-Estradiol (E2) has been reported to protect annulus fibrosus (AF) cells in vitro against interleukin-1β (IL-1β)-induced apoptosis in a concentration-dependent manner. However, its time-response effect remains unexplored. In addition, integrin α2/collagen II interaction has been reported to influence the apoptosis of nucleus pulposus cells in vitro. Thus, we hypothesized that integrin α1/collagen II might play a role in exerting the anti-apoptosis effect by E2. The aim of the current study was to further investigate the anti-apoptotic effect of E2 and determine the role of integrin a1/collagen II interaction. MATERIAL AND METHODS Rat AF cells were primary cultured and used for the following experiments. AF cells were identified by immunocytochemistry of type I collagen. Cell apoptosis was detected by fluorescence-activated cell sorter (FACS) analysis. The activity of active caspase-3 was determined by use of a caspase-3 detection kit. AF cell adhesion to type I collagen was determined by cell adhesion assay. Protein level of integrin subunit α1 was quantified by Western blot and mRNA expression was determined by real-time qPCR. RESULTS The immunocytochemistry of type I collagen revealed that cell purity was eligible for the following experiments with 98% of purity. FACS analysis indicated time-dependent anti-apoptosis effect of E2 at time points of 6 h, 12 h, and 24 h, which was confirmed by Caspase-3 activity. Furthermore, cell adhesion assay showed that E2 significantly increased cell binding to 95% of control, and qPCR and Western blot analysis showed that E2 effectively upregulated integrin α1. However, estrogen receptor antagonist ICI182780 prohibited the effect of E2. CONCLUSIONS This study shows that E2 protects against apoptosis in a time-dependent manner, and α1 integrin-mediated adhesion to collagen II is essential for estrogen-dependent anti-apoptosis in rat annulus fibrosus cells in vitro.

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#27081861   2016/05/10 Save this To Up

KLF8 Promotes Temozolomide Resistance in Glioma Cells via β-Catenin Activation.

The transcription factor Krüppel-like factor (KLF) 8 plays important roles in tumorigenesis and tumor metastasis. However, the relationship between KLF8 and glioma cell chemoresistance is not known.

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