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Autophagy and PI3K-Akt

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https://www.readbyqxmd.com/read/28199731/proteomic-profiling-analysis-reveals-a-link-between-experimental-autoimmune-uveitis-and-complement-activation-in-rats
#1
Dadong Guo, Bing Hu, Hongying Tang, Yuanyuan Sun, Bin Liu, Qingmei Tian, Hongsheng Bi
Uveitis is an autoimmune disease that usually damages the vision function, leading to poor visual quality in patients. As an autoimmune ocular inflammatory disease, the pathogenesis of uveitis is associated with abnormal expression of some proteins and aberrant regulation of multiple signaling pathways. Nevertheless, the detailed mechanism remains unclear. In this study, we induced an experimental autoimmune uveitis (EAU) model in rats. We determined the levels of C3a and membrane attack complex C5b-9 (soluble C5b-9, sC5b-9) in both plasma and aqueous humor, identified the differentially expressed proteins in plasma by liquid chromatography-tandem mass spectrometry, and employed bioinformatics algorithms to analyze differentially expressed proteins in EAU rat plasma...
February 15, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28198521/sevoflurane-ameliorates-doxorubicin-induced-myocardial-injury-by-affecting-the-phosphorylation-states-of-proteins-in-pi3k-akt-mtor-signaling-pathway
#2
Yini Wu, Jianping Wang, Xiaoyan Yu, Dongli Li, Xin Han, Lihua Fan
BACKGROUND: The effect of sevoflurane on the doxorubicin-induced myocardial injury was explored by investigating the phosphorylation states of proteins in phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway. METHODS: Myocardial injury rat models were induced by doxorubicin and evenly assigned into five groups according to different treatment: Doxorubicin group (DG, 200-µL saline solution), sevoflurane group (SevG, inhaled with 2...
February 15, 2017: Cardiology Journal
https://www.readbyqxmd.com/read/28197628/resveratrol-induced-autophagy-and-apoptosis-in-cisplatin-resistant-human-oral-cancer-car-cells-a-key-role-of-ampk-and-akt-mtor-signaling
#3
Chao-Hsiang Chang, Chao-Ying Lee, Chi-Cheng Lu, Fuu-Jen Tsai, Yuan-Man Hsu, Je-Wei Tsao, Yu-Ning Juan, Hong-Yi Chiu, Jai-Sing Yang, Ching-Chiung Wang
Resveratrol is known to be an effective chemo-preventive phytochemical against multiple tumor cells. However, the increasing drug resistance avoids the cancer treatment in oral cavity cancer. In this study, we investigated the oral antitumor activity of resveratrol and its mechanism in cisplatin-resistant human oral cancer CAR cells. Our results demonstrated that resveratrol had an extremely low toxicity in normal oral cells and provoked autophagic cell death to form acidic vesicular organelles (AVOs) and autophagic vacuoles in CAR cells by acridine orange (AO) and monodansylcadaverine (MDC) staining...
January 30, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28191279/ros-dependent-activation-of-autophagy-through-the-pi3k-akt-mtor-pathway-is-induced-by-hydroxysafflor-yellow-a-sonodynamic-therapy-in-thp-1-macrophages
#4
Yueqing Jiang, Jiayuan Kou, Xiaobo Han, Xuesong Li, Zhaoyu Zhong, Zhongni Liu, Yinghong Zheng, Ye Tian, Liming Yang
Monocyte-derived macrophages participate in infaust inflammatory responses by secreting various types of proinflammatory factors, resulting in further inflammatory reactions in atherosclerotic plaques. Autophagy plays an important role in inhibiting inflammation; thus, increasing autophagy may be a therapeutic strategy for atherosclerosis. In the present study, hydroxysafflor yellow A-mediated sonodynamic therapy was used to induce autophagy and inhibit inflammation in THP-1 macrophages. Following hydroxysafflor yellow A-mediated sonodynamic therapy, autophagy was induced as shown by the conversion of LC3-II/LC3-I, increased expression of beclin 1, degradation of p62, and the formation of autophagic vacuoles...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28181145/low-after-high-glucose-down-regulated-cx43-in-h9c2-cells-by-autophagy-activation-via-cross-regulation-by-the-pi3k-akt-mtor-and-mek-erk1-2-signal-pathways
#5
Yaguang Bi, Guangyu Wang, Xiangdong Liu, Meng Wei, Qingyong Zhang
PURPOSE: Hypoglycemia in diabetes is a strong predictor of cardiovascular events. High-glucose have been reported to alter connexin43 expression and to promote autophagy in cardiomyocytes. We investigated whether low-after-high glucose would influence connexin43 expression and autophagy in H9c2 cells. METHODS: H9c2 cells were incubated in 33.3 mM glucose for 24 h followed by 2.5 mM glucose for 2, 4, 6, or 12 h with or without chloroquine (autophagy inhibitor), U0126 (MEK1/2 inhibitor) or LY294002 (PI3K inhibitor)...
February 8, 2017: Endocrine
https://www.readbyqxmd.com/read/28177128/the-sgk1-inhibitor-si113-induces-autophagy-apoptosis-and-endoplasmic-reticulum-stress-in-endometrial-cancer-cells
#6
Domenico Conza, Paola Mirra, Gaetano Calì, Teresa Tortora, Luigi Insabato, Francesca Fiory, Silvia Schenone, Rosario Amato, Francesco Beguinot, Nicola Perrotti, Luca Ulianich
Endometrial cancer is often characterized by PI3K/AKT pathway deregulation. Recently it has been suggested that SGK1, a serine/threonine protein kinase that shares structural and functional similarities with the AKT family, might play a role in cancer, since its expression and/or activity has been found to be deregulated in different human tumors. However, the role of SGK1 in endometrial cancer has been poorly investigated. Here we show that SGK1 expression is increased in tissue specimens from neoplastic endometrium...
February 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28151484/berbamine-postconditioning-protects-the-heart-from-ischemia-reperfusion-injury-through-modulation-of-autophagy
#7
Yanjun Zheng, Shanshan Gu, Xuxia Li, Jiliang Tan, Shenyan Liu, Yukun Jiang, Caimei Zhang, Ling Gao, Huang-Tian Yang
Pretreatment of berbamine protects the heart from ischemia/reperfusion (I/R) injury. However it is unknown whether it has cardioprotection when given at the onset of reperfusion (postconditioning (PoC)), a protocol with more clinical impact. Autophagy is upregulated in I/R myocardium and exacerbates cardiomyocyte death during reperfusion. However, it is unknown whether the autophagy during reperfusion is regulated by berbamine. Here we investigated whether berbamine PoC (BMPoC) protects the heart through regulation of autophagy by analyzing the effects of BMPoC on infarct size and/or cell death, functional recovery and autophagy in perfused rat hearts and isolated cardiomyocytes subjected to I/R...
February 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28149534/iapp-modulates-cellular-autophagy-apoptosis-and-extracellular-matrix-metabolism-in-human-intervertebral-disc-cells
#8
Xinghuo Wu, Yu Song, Wei Liu, Kun Wang, Yong Gao, Shuai Li, Zhenfeng Duan, Zengwu Shao, Shuhua Yang, Cao Yang
The pathogenic process of intervertebral disc degeneration (IDD) is characterized by imbalance in the extracellular matrix (ECM) metabolism. Nucleus pulposus (NP) cells have important roles in maintaining the proper structure and tissue homeostasis of disc ECM. These cells need adequate supply of glucose and oxygen. Islet amyloid polypeptide (IAPP) exerts its biological effects by regulating glucose metabolism. The purpose of this study was to investigate the expression of IAPP in degenerated IVD tissue, and IAPP modulation of ECM metabolism in human NP cells, especially the crosstalk mechanism between apoptosis and autophagy in these cells...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28147244/the-pi3k-inhibitor-gdc-0941-enhances-radiosensitization-and-reduces-chemoresistance-to-temozolomide-in-gbm-cell-lines
#9
Fei Shi, Hongchuan Guo, Rong Zhang, Hongyu Liu, Liangliang Wu, Qiyan Wu, Jialin Liu, Tianyi Liu, Qiuhang Zhang
Glioblastoma multiforme (GBM) is among the most lethal of all human tumors. It is the most frequently occurring malignant primary brain tumor in adults. The current standard of care (SOC) for GBM is initial surgical resection followed by treatment with a combination of temozolomide (TMZ) and ionizing radiation (IR). However, GBM has a dismal prognosis, and survivors have compromised quality of life owing to the adverse effects of radiation. GBM is characterized by overt activity of the phosphoinositide 3-kinase (PI3K) signaling pathway...
January 29, 2017: Neuroscience
https://www.readbyqxmd.com/read/28115590/akt-signaling-pathway-in-macrophage-activation-and-m1-m2-polarization
#10
REVIEW
Eleni Vergadi, Eleftheria Ieronymaki, Konstantina Lyroni, Katerina Vaporidi, Christos Tsatsanis
Macrophages become activated initiating innate immune responses. Depending on the signals, macrophages obtain an array of activation phenotypes, described by the broad terms of M1 or M2 phenotype. The PI3K/Akt/mTOR pathway mediates signals from multiple receptors including insulin receptors, pathogen-associated molecular pattern receptors, cytokine receptors, adipokine receptors, and hormones. As a result, the Akt pathway converges inflammatory and metabolic signals to regulate macrophage responses modulating their activation phenotype...
February 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28112381/notoginsenoside-r1-attenuates-glucose-induced-podocyte-injury-via-the-inhibition-of-apoptosis-and-the-activation-of-autophagy-through-the-pi3k-akt-mtor-signaling-pathway
#11
Guodong Huang, Bingyu Zou, Jianzhen Lv, Tongyu Li, Guoli Huai, Shaowei Xiang, Shilong Lu, Huan Luo, Yaping Zhang, Yi Jin, Yi Wang
Injury to terminally differentiated podocytes contributes ignificantly to proteinuria and glomerulosclerosis. The aim of this study was to examine the protective effects of notoginsenoside R1 (NR1) on the maintenance of podocyte number and foot process architecture via the inhibition of apoptosis, the induction of autophagy and the maintenance pf podocyte biology in target cells. The effects of NR1 on conditionally immortalized human podocytes under high glucose conditions were evaluated by determining the percentage apoptosis, the percentage autophagy and the expression levels of slit diaphragm proteins...
January 20, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28106737/a-novel-combination-rnai-toward-warburg-effect-by-replacement-with-mir-145-and-silencing-of-ptbp1-induces-apoptotic-cell-death-in-bladder-cancer-cells
#12
Tomoaki Takai, Yuki Yoshikawa, Teruo Inamoto, Koichiro Minami, Kohei Taniguchi, Nobuhiko Sugito, Yuki Kuranaga, Haruka Shinohara, Minami Kumazaki, Takuya Tsujino, Kiyoshi Takahara, Yuko Ito, Yukihiro Akao, Haruhito Azuma
Bladder cancer is one of the most difficult malignancies to control. We explored the use of a novel RNA-interference method for a driver oncogene regulating cancer specific energy metabolism by the combination treatment with a small interfering RNA (siRNA) and a microRNA. After transfection of T24 and 253JB-V cells with miR-145 and/or siR-PTBP1, we examined the effects of cell growth and gene expression by performing the trypan blue dye exclusion test, Western blot, Hoechst 33342 staining, reverse transcription polymerase chain reaction (RT-PCR), and electron microscopy...
January 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28105213/wogonin-induces-beclin-1-pi3k-and-reactive-oxygen-species-mediated-autophagy-in-human-pancreatic-cancer-cells
#13
Shao-Jun Li, Shi-Jie Sun, Jie Gao, Fu-Bo Sun
Wogonin is considered to be an inhibitor of myeloid cell leukemia 1 and B-cell lymphoma 2, and a potential antitumor drug due to its ability to induce apoptosis in certain cancer cells; however, few previous studies have reported on wogonin-induced autophagy. The aim of the present study was to investigate the influence of wogonin on autophagy in human pancreatic cancer cells (HPCCs), elucidate its mechanism, and identify strategies to increase its effectiveness as an anti-cancer treatment. HPCCs were treated with wogonin and autophagy was detected in the cells...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28102849/berberine-sonodynamic-therapy-induces-autophagy-and-lipid-unloading-in-macrophage
#14
Jiayuan Y Kou, Ying Li, Zhaoyu Y Zhong, Yueqing Q Jiang, Xuesong S Li, Xiaobo B Han, Zhongni N Liu, Ye Tian, Liming M Yang
Impaired autophagy in macrophages accompanies the progression of atherosclerosis and contributes to lipid loading in plaques and ineffective lipid degradation. Therefore, evoking autophagy and its associated cholesterol efflux may provide a therapeutic treatment for atherosclerosis. In the present study, berberine-mediated sonodynamic therapy (BBR-SDT) was used to induce autophagy and cholesterol efflux in THP-1 macrophages and derived foam cells. Following BBR-SDT, autophagy was increased in the macrophages, autophagy resistance in the foam cells was prevented, and cholesterol efflux was induced...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28092744/quercetin-induces-apoptosis-and-autophagy-in-primary-effusion-lymphoma-cells-by-inhibiting-pi3k-akt-mtor-and-stat3-signaling-pathways
#15
Marisa Granato, Celeste Rizzello, Maria Saveria Gilardini Montani, Laura Cuomo, Marina Vitillo, Roberta Santarelli, Roberta Gonnella, Gabriella D'Orazi, Alberto Faggioni, Mara Cirone
Quercetin, a bioflavonoid contained in several vegetables daily consumed, has been studied for long time for its antiinflammatory and anticancer properties. Quercetin interacts with multiple cancer-related pathways such as PI3K/AKT, Wnt/β-catenin and STAT3. These pathways are hyperactivated in primary effusion lymphoma (PEL), an aggressive B cell lymphoma whose pathogenesis is strictly linked to the oncogenic virus Kaposis' Sarcoma-associated Herpesvirus (KSHV). In this study, we found that quercetin inhibited PI3K/AKT/mTOR and STAT3 pathways in PEL cells, and as a consequence, it down-regulated the expression of the prosurvival cellular proteins such as c-FLIP, cyclin D1 and cMyc...
January 5, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28087295/postconditioning-induced-neuroprotection-mechanisms-and-applications-in-cerebral-ischemia
#16
REVIEW
Yan-Ying Fan, Wei-Wei Hu, Fang Nan, Zhong Chen
Ischemic postconditioning (PostC) is defined as a series of rapid intermittent interruptions of blood flow at the phase of reperfusion, which produces neuroprotection against cerebral ischemia/reperfusion injury via mobilizing the brain's own endogenous adaptive mechanisms. Now the concept of conventional ischemic PostC has been extended to limb remote ischemic PostC and chemical PostC with hypoxia, volatile anesthetic, CO2, etc. According to the different temporal profile of PostC, it is divided into rapid and delayed PostC...
January 10, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28078994/modulation-of-tumour-related-signaling-pathways-by-natural-pentacyclic-triterpenoids-and-their-semisynthetic-derivatives
#17
Andrey V Markov, Evgeniya B Logashenko, Marina A Zenkova
Pentacyclic triterpenoids are a large class of natural isoprenoids that are widely biosynthesized in higher plants. These compounds are potent anticancer agents that exhibit antiproliferative, antiangiogenic, antiinflammatory and proapoptotic activities. Although their effects on multiple pathways have been reported, unifying mechanisms of action have not yet been established. To date, a huge number of semisynthetic derivatives have been synthesized in different laboratories on the basis of triterpenoid scaffolds, and many have been assayed for their biological activities...
January 12, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28072480/free-fatty-acids-induce-autophagy-and-lox-1-upregulation-in-cultured-aortic-vascular-smooth-muscle-cells
#18
Cheng-I Cheng, Yueh-Hong Lee, Po-Han Chen, Yu-Chun Lin, Ming-Huei Chou, Ying-Hsien Kao
Elevation of free fatty acids (FFAs) is known to affect microvascular function and contribute to obesity-associated insulin resistance, hypertension, and microangiopathy. Proliferative and synthetic vascular smooth muscle cells (VSMCs) increase intimal thickness and destabilize atheromatous plaques. This study aimed to investigate whether saturated palmitic acid (PA) and monounsaturated oleic acid (OA) modulate autophagy activity, cell proliferation, and vascular tissue remodeling in an aortic VSMC cell line...
November 5, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28061438/combination-of-arsenic-trioxide-and-everolimus-rad001-synergistically-induces-both-autophagy-and-apoptosis-in-prostate-cancer-cells
#19
Sheng Tai, Lingfan Xu, Ming Xu, Ligang Zhang, Yangyang Zhang, Kaipin Zhang, Li Zhang, Chaozhao Liang
The inhibitor of PI3K-AKT-mTOR pathway, such as Rad001, has not shown therapeutic efficacy as a single agent in prostate cancer. Arsenic trioxide induces the autophagic pathway in prostate cancer cells. We identified Arsenic trioxide can synergize with Rad001 to induce cytotoxicity of prostate cancer cells. Moreover, we identified synergistic induction of autophagy and apoptosis as the underlying mechanism. This enhanced autophagic cell death is accompanied by increased Beclin1 mRNA stability as well as upregulation of ATG5-ATG12 conjugate, Beclin1, and LC3-2...
January 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28049093/regulation-of-different-components-from-ophiopogon-japonicus-on-autophagy-in-human-lung-adenocarcinoma-a549cells-through-pi3k-akt-mtor-signaling-pathway
#20
Juan Chen, Jiarui Yuan, Liqiang Zhou, Maomao Zhu, Ziqi Shi, Jie Song, Qingyu Xu, Guowen Yin, You Lv, Yi Luo, Xiaobin Jia, Liang Feng
Autophagy plays a dual role in the development of cancer, acting as both a tumor suppressor and a cell survival inducer. Ophiopogon japonicus (L.f) Ker-Gawl (OJ), as a traditional Chinese medicine, specially possesses remarkable anti-cancer activity in the clinical. Previously, studies have indicated that flavonoids (FOJ) and steroidal saponins (SSOJ) are the main active substances of OJ. However, the effects of FOJ and SSOJ on autophagy of A549 cells have not been fully elucidated. In this study, we found that the expressions of autophagy-related mediators (LC3-II/LC3-I ratio, Atg-3, Atg-7 and Beclin-1) were increased in A549 cells by the treatment with FOJ (7...
December 31, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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