The crosstalk between p38 and Akt signaling pathways orchestrates EMT by regulating SATB2 expression in NSCLC cells

Epithelial–mesenchymal transition is a crucial event for metastasis and could be mediated by several pathways such as phosphoinositide 3-kinase/Akt, mitogen-activated protein kinases, as well as many epigenetic regulators. Special AT-rich sequence-binding protein 2 is an epigenetic regulator involved in epithelial–mesenchymal transition and osteoblastic differentiation. It has been reported that the crosstalk between several pathways is responsible for the regulation of epithelial–mesenchymal transition in cancer cells. However, crosstalks between p38 and Akt pathways involved in epithelial–mesenchymal transition are still unknown. We recently reported that there is a crosstalk between p38 and Akt pathways in non-small-cell lung carcinoma cells, and this crosstalk is associated with E-cadherin and special AT-rich sequence-binding protein 2 expressions. Therefore, we aimed to determine whether this crosstalk has a mediator role in the regulation of epithelial–mesenchymal transition in non-small-cell lung carcinoma. Our results showed that inhibition of p38 leads to the disruption of this crosstalk via decreased expression of phosphatase and tensin homolog (PTEN) and subsequently increased activation of Akt in non-small-cell lung carcinoma cells. Then, we found that p38 inhibition upregulated special AT-rich sequence-binding protein 2 expression and reversed epithelial–mesenchymal transition in non-small-cell lung carcinoma cells. Furthermore, special AT-rich sequence-binding protein 2 knockdown abolished the effect of p38 inhibition on epithelial–mesenchymal transition in non-small-cell lung carcinoma cells. In conclusion, our results strongly indicate that the crosstalk between p38 and Akt pathways can determine special AT-rich sequence-binding protein 2 expression and epithelial character of non-small-cell lung carcinoma cells, and special AT-rich sequence-binding protein 2 is a critical epigenetic regulator for epithelial–mesenchymal transition mediated by p38 pathway in non-small-cell lung carcinoma. Our findings will contribute to illuminate the molecular mechanisms of the epithelial–mesenchymal transition process that has a critical significance for lung cancer metastasis. © 2017, © The Author(s) 2017

Tumour suppressor PTEN enhanced enzyme activity of GPx, SOD and catalase by suppression of PI3K/AKT pathway in non-small cell lung cancer cell lines

Phosphates and tensin homologue deleted on chromosome 10 (PTEN) is a tumour suppressor gene which dephosphorilates phosphoinositol 3,4,5 triphosphates. Therefore PTEN can regulate PI3K/AKT pathway in cells. Because of promoter methylation or gene deletion, PTEN expression is commonly decreased or lost in non-small cell lung cancer (NSCLC) cell lines. Therefore, we hypothesized that PTEN could regulate the activity of superoxide dismutase (CuZnSOD), glutathione peroxidase (GPx) and catalase. We first recreated PTENwt, G129R and G129E expressions in lung cell lines, in which endogenous PTEN expression was not detected. Then, we showed that PTEN could suppress AKT activity by its lipid phosphatase domain. We then examined the effect of recreated PTEN expressions in NSCLC cells. While PTENwt expression caused enhanced activity of SOD, GPx and catalase in transfected cells lines, neither G129R nor G129E expression effected enzyme activities. These results suggest that PTEN can up-regulate SOD, GPx and catalase activity by inhibition of PI3K/AKT pathway in NSCLC cell lines. © 2013 Informa UK, Ltd

Protective effect of insulin and glucose at different concentrations on penicillin-induced astrocyte death on the primer astroglial cell line

Astrocytes perform many functions in the brain and spinal cord. Glucose metabolism is important for astroglial cells and astrocytes are the only cells with insulin receptors in the brain. The common antibiotic penicillin is also a chemical agent that causes degenerative effect on neuronal cell. The aim of this study is to show the effect of insulin and glucose at different concentrations on the astrocyte death induced by penicillin on primer astroglial cell line. It is well known that intracranial penicillin treatment causes neuronal cell death and it is used for experimental epilepsy model commonly. Previous studies showed that insulin and glucose might protect neuronal cell in case of proper concentrations. But, the present study is about the effect of insulin and glucose against astrocyte death induced by penicillin. For this purpose, newborn rat brain was extracted and then mechanically dissociated to astroglial cell suspension and finally grown in culture medium. Clutters were maintained for 2 weeks prior to being used in these experiments. Different concentrations of insulin (0, 1, 3 nM) and glucose (0, 3, 30 mM) were used in media without penicillin and with 2 500 μM penicillin. Penicillin decreased the viability of astroglial cell seriously. The highest cell viability appeared in medium with 3 nM insulin and 3 mM glucose but without penicillin. However, in medium with penicillin, the best cell survival was in medium with 1 nM insulin but without glucose. We concluded that insulin and glucose show protective effects on the damage induced by penicillin to primer astroglial cell line. Interestingly, cell survival depends on concentrations of insulin and glucose strongly. The results of this study will help to explain cerebrovascular pathologies parallel to insulin and glucose conditions of patient after intracranial injuries. © 2012, Editorial Board of Neural Regeneration Research. All rights reserved

Yakıotunun Ksenobiyotik Metabolizması Üzerine Etkilerinin ve İlaç-Diyet Etkileşim Potansiyelinin Proteomik ve Moleküler Yaklaşımlar ile Aydınlatılması

TÜBİTAK TBAG Proje15.05.201

The effects of organizational culture and leadership on firm performance

The aim of this study is to investigate whether the organizational culture and leadership have an effect on performance. The literature search displays that these three subjects are usually studied on their own. The effects of organizational culture, leadership and performance on each other are not sufficiently tackled. Thus, this study intends to help filling this gap. The impact of organizational culture and leadership over performance is examined with the assistance of survey data. The main mass of the survey is represented by the managers of a shopping mall. As a result of these analyzes; organizational culture and leadership, organizational culture and performance, leadership and performance were found to have a meaningful relationship. It was found that organizational culture and leadership had effects on firm performance

The effectsof organizational cultureand leadership on firm performance

Bu çalışmanın amacı, örgüt kültürü ve liderliğin performans üzerindeki etkisinin araştırılmasıdır. Yapilan literatür taramasında söz konusu üç konunun genellikle tek başına ele alındığı görülmüştür. Örgüt kültürü, liderlik ve performansın birbirleri üzerindeki etkilerinin incelendiği çalışmaların olmadığı tespit edilmiştir. Bu çalışmada örgüt kültürü ve liderliğin performans üzerindeki etkileri araştırılmıştır. Örgüt kültürü ve liderliğin performansa etkisi, anketle incelenmistir. Uygulanan anketin ana kütlesini bir alışveris merkezinin yoneticileri teşkil etmektedir. Yapilan analizler sonucunda: örgüt kültürü ile liderlik, örgüt kültürü ile performans ve liderlik ile performans arasında anlamlı bir ilişki olduğu görülmüş, örgüt kültürüi ile liderliğinde performans üzerinde etkili olduğu bulgusuna ulaşılmıştır