scholarly journals The Major Target of the Endogenously Generated Reactive Oxygen Species in Response to Insulin Stimulation Is Phosphatase and Tensin Homolog and Not Phosphoinositide-3 Kinase (PI-3 Kinase) in the PI-3 Kinase/Akt Pathway

2005 ◽  
Vol 16 (1) ◽  
pp. 348-357 ◽  
Author(s):  
Ji Hae Seo ◽  
Younghee Ahn ◽  
Seung-Rock Lee ◽  
Chang Yeol Yeo ◽  
Kyu Chung Hur
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Lines ◽  
Membrane Fraction ◽  
Akt Pathway ◽  
Oxygen Species ◽  
Insulin Stimulation ◽  
Phosphatase And Tensin Homolog ◽  
Downstream Signaling ◽  
Tensin Homolog ◽  
Phosphoinositide 3 Kinase

Phosphoinositide-3 kinase (PI-3 kinase) and its downstream signaling molecules PDK-1 and Akt were analyzed in SK-N-SH and SK-N-BE(2) human neuroblastoma cell lines. When cells were stimulated with insulin, PI-3 kinase was activated in both cell lines, whereas the translocation of PDK-1 to the membrane fraction and phosphorylated Akt were observed only in SK-N-SH cells. Analyses of the insulin-mediated reactive oxygen species (ROS) generation and Phosphatase and Tensin homolog (PTEN) oxidation indicate that PTEN oxidation occurred in SK-N-SH cells, which can produce ROS, but not in SK-N-BE(2) cells, which cannot increase ROS in response to insulin stimulation. When SK-N-SH cells were pretreated with the NADPH oxidase inhibitor diphenyleneiodonium chloride before insulin stimulation, insulin-mediated translocation of PDK-1 to the membrane fraction and phosphorylation of Akt were remarkably reduced, whereas PI-3 kinase activity was not changed significantly. These results indicate that not only PI-3 kinase activation but also inhibition of PTEN by ROS is needed to increase cellular level of phosphatidylinositol 3,4,5-trisphosphate for recruiting downstream signaling molecules such as PDK-1 and Akt in insulin-mediated signaling. Moreover, the ROS generated by insulin stimulation mainly contributes to the inactivation of PTEN and not to the activation of PI-3 kinase in the PI-3 kinase/Akt pathway.

Copper Ions Strongly Activate the Phosphoinositide-3-Kinase/Akt Pathway Independent of the Generation of Reactive Oxygen Species

2002 ◽  
Vol 397 (2) ◽  
pp. 232-239 ◽  
Author(s):  
Elena A. Ostrakhovitch ◽  
Mohammad Reza Lordnejad ◽  
Freimut Schliess ◽  
Helmut Sies ◽  
Lars-Oliver Klotz
Keyword(s):  
Reactive Oxygen Species ◽  
Copper Ions ◽  
Reactive Oxygen ◽  
Akt Pathway ◽  
Oxygen Species ◽  
Phosphoinositide 3 Kinase

scholarly journals An Immunohistochemical Study of the PTEN/AKT Pathway Involvement in Canine and Feline Mammary Tumors

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 365
Author(s):  
Pietro Asproni ◽  
Francesca Millanta ◽  
Lorenzo Ressel ◽  
Fabio Podestà ◽  
Francesca Parisi ◽  
...  
Keyword(s):  
Immunohistochemical Study ◽  
Lymphatic Invasion ◽  
Pten Expression ◽  
Akt Pathway ◽  
Phosphatase And Tensin Homolog ◽  
Mammary Carcinomas ◽  
Tensin Homolog ◽  
Aggressive Tumors ◽  
Aggressive Subtype ◽  
Viral Oncogene Homolog

Phosphatase and tensin homolog deleted on chromosome10 (PTEN), phospho-v-Akt murine thymoma viral oncogene homolog (AKT), and the Rapamycin-Insensitive Companion of mTOR (Rictor) expression was investigated by immunohistochemistry in 10 canine mammary adenomas (CMAs), 40 canine mammary carcinomas (CMCs), and 30 feline mammary carcinomas (FMCs). All the CMAs, 25 of 40 CMCs (63%) and 7 of 30 FMCs (23%), were PTEN-positive. In dogs, no CMAs and 15 of 25 CMCs (37%) expressed phospho-AKT (p-AKT), while 24 of 30 FMCs (82%) were p-AKT-positive. One of 10 CMAs (10%), 24 of 40 CMCs (60%) and 20 of 30 FMCs (67%) were Rictor-positive. In the dog, PTEN expression correlated with less aggressive tumors, absence of lymphatic invasion, and longer survival. P-AKT expression correlated with more aggressive subtype, lymphatic invasion, and poorer survival and Rictor expression with lymphatic invasion. In cats, PTEN correlated with less aggressive carcinomas, absence of lymphatic invasion, and better survival. P-AKT and Rictor expression correlated with poorer survival. PTEN expression was inversely correlated with p-AKT and Rictor in both species, while p-AKT positively correlated with Rictor expression. A strong PTEN/AKT pathway involvement in behavior worsening of CMT and FMTs is demonstrated, providing a rationale for further studies of this pathway in veterinary oncology.

scholarly journals Esthetic and Functional Improvement of Asymmetric Lower Limb Overgrowth in a Proteus Syndrome Patient: a Combined Surgical Technique

2021 ◽  
Author(s):  
Francesca Riccardi ◽  
Simone Catapano ◽  
Giuseppe Cottone ◽  
Dino Zilio ◽  
Luca Vaienti
Keyword(s):  
Adipose Tissue ◽  
Lower Limb ◽  
Vascular Malformations ◽  
Functional Improvement ◽  
Proteus Syndrome ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Genetic Mosaicism ◽  
Phosphoinositide 3 Kinase ◽  
The Right

AbstractProteus syndrome is a rare, sporadic, congenital syndrome that causes asymmetric and disproportionate overgrowth of limbs, connective tissue nevi, epidermal nevi, alteration of adipose tissue, and vascular malformations. Genetic mosaicism, such as activating mutations involving protein kinase AKT1, phosphoinositide 3 kinase (PI3-K), and phosphatase and tensin homolog (PTEN), may be important causes of Proteus syndrome. However, many patients have no evidence of mutations in these genes. Currently, the diagnosis is clinical and based on phenotypic features. This article reports a case of Proteus syndrome in a 14-year-old female patient who presented with linear epidermal nevi, viscera anomalies, and adipose tissue dysregulation. She showed an asymmetric progressive overgrowth of the right lower limb after birth bringing relevant functional and esthetic consequences. Therefore, she asked a plastic surgery consultation and a surgical treatment with a combined technique was planned. With our approach, we were able to reduce leg diameter and improve joint mobility reliably and safely with satisfying esthetic results.

Real-time monitoring of reactive oxygen species production during differentiation of human monocytic cell lines (THP-1)

2005 ◽  
Vol 549 (1-2) ◽  
pp. 14-19 ◽  
Author(s):  
Shigenobu Kasai ◽  
Hitoshi Shiku ◽  
Yu-suke Torisawa ◽  
Hiroyuki Noda ◽  
Jun Yoshitake ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Real Time ◽  
Cell Lines ◽  
Reactive Oxygen Species Production ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Real Time Monitoring ◽  
Monocytic Cell ◽  
Human Monocytic Cell ◽  
Species Production

scholarly journals AKT but not MYC promotes reactive oxygen species-mediated cell death in oxidative culture

2019 ◽  
Author(s):  
Dongqing Zheng ◽  
Jonathan H. Sussman ◽  
Matthew P. Jeon ◽  
Sydney T. Parrish ◽  
Alireza Delfarah ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Reactive Oxygen Species ◽  
Cell Death ◽  
Oxidative Phosphorylation ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Oxygen Species

ABSTRACTOncogenes can generate metabolic vulnerabilities in cancer cells. Here, we tested how AKT and MYC affect the ability of cells to shift between respiration and glycolysis. Using immortalized mammary epithelial cells, we discovered that constitutively active AKT but not MYC induced cell death in galactose culture, where cells must rely on oxidative phosphorylation for energy generation. However, the negative effects of AKT were short-lived, and AKT-expressing cells recommenced growth after ~15 days in galactose. To identify the mechanisms regulating AKT-mediated cell death, we used metabolomics and found that AKT cells dying in galactose upregulated glutathione metabolism. Next, using proteomics, we discovered that AKT-expressing cells dying in galactose upregulated nonsense-mediated mRNA decay, a marker of sensitivity to oxidative stress. We therefore measured levels of reactive oxygen species (ROS) and discovered that galactose induced ROS in cells expressing AKT but not MYC. Additionally, ROS were required for the galactose-induced death of AKT-expressing cells. We then tested whether these findings could be replicated in breast cancer cell lines with constitutively active AKT signaling. Indeed, we found that galactose induced rapid cell death in breast cancer cell lines and that ROS were required for galactose-induced cell death. Together, our results demonstrate that AKT but not MYC induces a metabolic vulnerability in cancer cells, namely the restricted flexibility to use oxidative phosphorylation.ImplicationsThe discovery that AKT but not MYC restricts the ability to utilize oxidative phosphorylation highlights that therapeutics targeting tumor metabolism must be tailored to the individual genetic profile of tumors.

scholarly journals Reduction of Intracellular-Reactive Oxygen Species and Diminished Mitogen-Activated Protein Kinases (MAPKs) Activation are Associated with Oral Squamous Cell Carcinoma Cell Aggressiveness

2017 ◽  
Vol 15 (2) ◽  
pp. 131-141
Author(s):  
Tanyarath UTAIPAN ◽  
Apsorn SATTAYAKHOM ◽  
Issara PRACHONGSAI ◽  
Nurdina CHARONG ◽  
Warangkana CHUNGLOK
Keyword(s):  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Protein Kinases ◽  
Cell Lines ◽  
Oxygen Species ◽  
Mitogen Activated Protein Kinases ◽  
Mitogen Activated Protein

Oral squamous cell carcinoma (OSCC) is a serious health problem in many countries. Several drugs have been used to treat head and neck and oral cavity cancers. However, the success rate has not been impressive because of the heterogeneity of cancerous cells, resulting in differential responsiveness to chemotherapy. Two distinct phenotypes of OSCC cells, the CLS-354/WT and CLS-354/DXcells, have been used as in vitro cell models for this study. CLS-354/DXcells were more aggressive than CLS-354/WTcells, supported by the observation that CLS-354/DXcells can undergo epithelial-mesenchymal transition (EMT), grow anchorage-independently, and increase invasiveness. We investigated the preliminary redox status of these 2 cell lines, including levels of reactive oxygen species (ROS) and cellular antioxidants, using flow cytometry analysis and ABTS+ free radical scavenging assay, respectively. A 7-fold decrease in ROS level was detected in CLS-354/DXcells, comparing with CLS-354/WTcells, while antioxidant capacity was not different from that of CLS-354/WT cells. Hydrogen peroxide, a ROS modulating agent, could induce ROS levels, and caused cell death in CLS-354/WT greater than that of CLS-354/DX cells. Of note, hydrogen peroxide-induced cytotoxicity could be rescued by N-acetyl cysteine, confirming ROS-mediated cytotoxicity in both cell lines. ROS-sensitive mitogen-activated protein kinases (MAPKs) were observed using immunoblot assay. The expressions of p-JNK1/2 and p-p38 MAPK in CLS-354/DX cells were absent, while these expressions were abundantly detected in CLS-354/WTcells. This suggests that lower ROS levels, with the concomitant reduction of JNK and p38 MAPK activation in CLS-354/DX cells, are associated with cancer cell aggressiveness. These findings provide significant evidence of the resistance to ROS-modulating agents in aggressive OSCC cells.

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