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Autophagy and PI3K-Akt

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https://www.readbyqxmd.com/read/29148068/gastrodin-protects-myocardial-cells-against-hypoxia-reoxygenation-injury-in-neonatal-rats-by-inhibiting-cell-autophagy-through-the-activation-of-mtor-signals-in-pi3k-akt-pathway
#1
Xiang Li, Qinhui Zhu, Yuanyuan Liu, Zhiyong Yang, Bin Li
OBJECTIVES: This study aimed to investigate the protective effect of gastrodin (GAS) on myocardial cells with hypoxia/reoxygenation (H/R) injury in neonatal rats and explore the underlying mechanism. METHODS: Myocardial cells were extracted from neonatal rats and divided into six groups: control, H/R, H/R + Low-Concentration GAS, H/R + Middle-Concentration GAS, H/R + High-Concentration GAS and H/R + High-Concentration GAS + AKT Inhibitor groups. After 48-h treatment, cell viability, autophagosome quantity and the expression levels of LC3-II, p62, Akt, pAkt, mammalian target of rapamycin (mTOR) and uncoordinated 51-like kinase 1 (ULK1) in myocardial cells were made comparisons among each group...
November 17, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/29147906/regulation-of-signal-transduction-by-dj-1
#2
Stephanie E Oh, M Maral Mouradian
The ability of DJ-1 to modulate signal transduction has significant effects on how the cell regulates normal processes such as growth, senescence, apoptosis, and autophagy to adapt to changing environmental stimuli and stresses. Perturbations of DJ-1 levels or function can disrupt the equilibrium of homeostatic signaling networks and set off cascades that play a role in the pathogenesis of conditions such as cancer and Parkinson's disease.DJ-1 plays a major role in various pathways. It mediates cell survival and proliferation by activating the extracellular signal-regulated kinase (ERK1/2) pathway and the phosphatidylinositol-3-kinase (PI3K)/Akt pathway...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29145153/the-pro-apoptosis-effect-of-sinomenine-in-renal-carcinoma-via-inducing-autophagy-through-inactivating-pi3k-akt-mtor-pathway
#3
Fei Deng, Yue-Xian Ma, Liang Liang, Ping Zhang, Jing Feng
Renal cell carcinoma (RCC) is a heterogeneous histological disease and the most common kidney cancer. The mortality rate of RCC remains high despite the improved treatment. Sinomenine is an isoquinoline extracted from Chinese medicinal plant Sinomenium acutum, famous for its ability to suppress several cancer cell types. Our research aimed to explore the anti-cancer potential of sinomenine in RCC. Results showed that sinomenine reduced the viability by reducing sphere-forming ability and enhancing pro-apoptosis effect in ACHN cells in a dose dependent manner...
November 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29138276/metabolic-reprogramming-ensures-cancer-cell-survival-despite-oncogenic-signaling-blockade
#4
Hui-Wen Lue, Jennifer Podolak, Kevin Kolahi, Larry Cheng, Soumya Rao, Devin Garg, Chang-Hui Xue, Juha K Rantala, Jeffrey W Tyner, Kent L Thornburg, Ann Martinez-Acevedo, Jen-Jane Liu, Christopher L Amling, Charles Truillet, Sharon M Louie, Kimberly E Anderson, Michael J Evans, Valerie B O'Donnell, Daniel K Nomura, Justin M Drake, Anna Ritz, George V Thomas
There is limited knowledge about the metabolic reprogramming induced by cancer therapies and how this contributes to therapeutic resistance. Here we show that although inhibition of PI3K-AKT-mTOR signaling markedly decreased glycolysis and restrained tumor growth, these signaling and metabolic restrictions triggered autophagy, which supplied the metabolites required for the maintenance of mitochondrial respiration and redox homeostasis. Specifically, we found that survival of cancer cells was critically dependent on phospholipase A2 (PLA2) to mobilize lysophospholipids and free fatty acids to sustain fatty acid oxidation and oxidative phosphorylation...
November 14, 2017: Genes & Development
https://www.readbyqxmd.com/read/29130967/endoplasmic-reticulum-stress-promotes-autophagy-and-apoptosis-and-reduces-chemotherapy-resistance-in-mutant-p53-lung-cancer-cells
#5
Ping-Ping Gan, Yang-Ying Zhou, Mei-Zuo Zhong, Yun Peng, Li Li, Jian-Huang Li
BACKGROUND/AIMS: Lung cancer (LC) continues to be one of the most prevalent cancers around the world. During this study we aimed to investigate the involvement of endoplasmic reticulum stress (ERS) in autophagy, apoptosis, and chemotherapy resistance of mutant p53 LC cells. METHODS: Immunohistochemistry was employed to help determine the p53 mutation status of cancer cells from 92 primary LC patients, who were subsequently assigned to either the mutant p53 (n = 39) or wild-type p53 group (n = 53)...
November 6, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29118925/bardoxolone-methyl-cddo-me-or-rta402-induces-cell-cycle-arrest-apoptosis-and-autophagy-via-pi3k-akt-mtor-and-p38-mapk-erk1-2-signaling-pathways-in-k562-cells
#6
Xin-Yu Wang, Xue-Hong Zhang, Li Peng, Zheng Liu, Yin-Xue Yang, Zhi-Xu He, Hong-Wan Dang, Shu-Feng Zhou
Chronic myeloid leukemia (CML) treatment remains a challenge due to drug resistance and severe side effect, rendering the need on the development of novel therapeutics. CDDO-Me (Bardoxolone methyl), a potent Nrf2 activator and NF-κB inhibitor, is a promising candidate for cancer treatment including leukemia. However, the underlying mechanism for CDDO-Me in CML treatment is unclear. This study aimed to evaluate the molecular interactome of CDDO-Me in K562 cells using the quantitative proteomics approach stable-isotope labeling by amino acids in cell culture (SILAC) and explore the underlying mechanisms using cell-based functional assays...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29115424/cornin-protects-sh%C3%A2-sy5y-cells-against-oxygen-and-glucose-deprivation%C3%A2-induced-autophagy-through-the-pi3k-akt-mtor-pathway
#7
Changling Ding, Jie Zhang, Baoyuan Li, Zhaoxing Ding, Wenna Cheng, Fei Gao, Ye Zhang, Yangyang Xu, Shuping Zhang
It has been reported that cornin may reduce neuronal death during cerebral ischemia; however, little is known about the molecular mechanism of the role of corninin autophagy in SH‑SY5Y neuronal cells. In the present study, oxygen‑glucose deprivation (OGD)‑treated cells were used as a cerebral ischemia model in vitro. The results demonstrated that cornin was able to reduce neuronal cell loss, increase the apoptosis regulator Bcl‑2/apoptosis regulator BAX ratio, and decrease the protein levels of caspase‑3...
October 25, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29111231/ros-akt-mtor-axis-mediates-autophagy-of-human-umbilical-vein-endothelial-cells-induced-by-cooking-oil-fumes-derived-fine-particulate-matters-in-vitro
#8
Rui Ding, Chao Zhang, Xiaoxia Zhu, Han Cheng, Furong Zhu, Yachun Xu, Ying Liu, Longping Wen, Jiyu Cao
Cooking oil fumes-derived PM2.5 (COFs-derived PM2.5) exposure can induce oxidative stress and cytotoxic effects. Here we investigated the role of ROS-AKT-mTOR axis in COFs-derived PM2.5-induced autophagy in human umbilical vein endothelial cells (HUVECs). HUVECs were treated with different concentrations of COFs-derived PM2.5, together with or without N-acetyl-L-cysteine (NAC, a radical scavenger) or 3-methyladenine (3-MA, an autophagy inhibitor). Cell viability was assessed with MTT assay, and ROS level was measured with DCFH-DA assay after the treatment...
October 28, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29107216/pharmacological-effects-and-potential-therapeutic-targets-of-dt-13
#9
REVIEW
Ghulam Jilany Khan, Mohsin Rizwan, Muhammad Abbas, Muhammad Naveed, Yu Boyang, Muhammad Ahsan Naeem, Sara Khan, Shengtao Yuan, Mirza Muhammad Faran Ashraf Baig, Li Sun
DT-13 is an isolated compound from Dwarf lillytruf tuber and currently among active research drugs by National Natural Science foundation of China for its several potential effects. The drug has been reported for its multiple pharmacological actions however no thorough review studies are available on it. Our present study is highlighting the pros and cons of DT-13 focusing on its potential pharmacological actions, therapeutic utilization and further exploration for novel targets. The drug possesses very low toxicity profile, quick onset and long duration of action with slow elimination that combinely makes it favorable for the clinical studies...
October 28, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29104499/erythropoietin-reduces-insulin-resistance-via-regulation-of-its-receptor-mediated-signaling-pathways-in-db-db-mice-skeletal-muscle
#10
Yu Pan, Xiu Hong Yang, Li Li Guo, Yan Hong Gu, Qing Yan Qiao, Hui Min Jin
Erythropoietin (EPO) can reduce insulin resistance (IR) in adipocytes; however, it is unknown whether EPO can decrease IR in skeletal muscle. Here we investigated whether EPO could reduce IR in type 2 diabetic mouse skeletal muscle and its possible signaling mechanisms of action. Twelve-week-old db/db diabetic mice were employed in this study. Systemic use of EPO improved glucose profiles in type 2 diabetic mice after 4 and 8 weeks treatment. EPO up-regulated EPOR protein expression in skeletal muscle, and subsequently activated downstream signaling molecules such as JAK2, IRS-1, PI3K, AKT, and eNOS...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/29101804/inhibition-of-mir-20-promotes-proliferation-and-autophagy-in-articular-chondrocytes-by-pi3k-akt-mtor-signaling-pathway
#11
Weidong He, Ye Cheng
Osteoarthritis is a common cause of functional deterioration in older adults and is an immense burden on the aging population. The molecular mechanism underlying the regulation of chondrocyte requires further elucidation, particularly with respect to the role of microRNAs. The aim of this study was to identify and characterize the expression of miR-20 in normal and OA chondrocytes, and to determine its role in OA pathogenesis. MiR-20 expression in cartilage specimens was examined in 30 patients with knee osteoarthritis and 30 traumatic amputees...
November 1, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29100552/cooperative-antitumor-activities-of-carnosic-acid-and-trastuzumab-in-erbb2-breast-cancer-cells
#12
Carolina D'Alesio, Grazia Bellese, Maria Cristina Gagliani, Cinzia Aiello, Elena Grasselli, Gianluca Marcocci, Angela Bisio, Sara Tavella, Tiziana Daniele, Katia Cortese, Patrizio Castagnola
BACKGROUND: ERBB2 is overexpressed in up to 20-30% of human breast cancers (BCs), and it is associated with aggressive disease. Trastuzumab (Tz), a humanized monoclonal antibody, improves the prognosis associated with ERBB2-amplified BCs. However, the development of resistance remains a significant challenge. Carnosic acid (CA) is a diterpene found in rosemary and sage, endowed with anticancer properties. In this in vitro study, we have investigated whether Tz and CA have cooperative effects on cell survival of ERBB2 overexpressing (ERBB2(+)) cells and whether CA might restore Tz sensitivity in Tz-resistant cells...
November 3, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29093603/pi3k-akt-mtor-pathway-in-ovarian-cancer-treatment-are-we-on-the-right-track
#13
Maria Luisa Gasparri, Erlisa Bardhi, Ilary Ruscito, Andrea Papadia, Ammad Ahmad Farooqi, Claudia Marchetti, Giorgio Bogani, Irene Ceccacci, Michael D Mueller, Pierluigi Benedetti Panici
The high recurrence rate and the low overall survival in ovarian cancer suggest that a more specific therapeutic approach in addition to conventional treatment is required. Translational and clinical research is investigating new molecular targets in order to find an alternative way to affect tumor growth and to minimize the overlap of toxicity of antiblastic agents. Given its implication in many cellular activities including regulation of cell growth, motility, survival, proliferation, protein synthesis, autophagy, transcription, as well as angiogenesis, PI3K/AKT/mTOR is one of the most investigated intracellular signaling pathways...
October 2017: Geburtshilfe und Frauenheilkunde
https://www.readbyqxmd.com/read/29091873/autophagy-participates-in-isoliquiritigenin-induced-melanin-degradation-in-human-epidermal-keratinocytes-through-pi3k-akt-mtor-signaling
#14
Zhibo Yang, Biyun Zeng, Yi Pan, Pan Huang, Chang Wang
Melanin is the pigment responsible for the color of human skin and hair. Melanin serves as a double-edge sword which can exert both protective and spot-causing effects on skin. Although melanin has an important role in protecting the skin against UV damage, an excessive or uneven melanin production can lead to the formation of freckles and age spots. Isoliquiritigenin (ISL) has been reported to inhibit melanin synthesis; however, its role in melanin degradation remains unclear. In the present study, we evaluated the detailed function of ISL in melanin degradation in human epidermal keratinocytes...
October 26, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29067015/serum-metabolic-alterations-upon-zika-infection
#15
Carlos Fernando O R Melo, Jeany Delafiori, Diogo N de Oliveira, Tatiane M Guerreiro, Cibele Z Esteves, Estela de O Lima, Victoria Pando-Robles, Rodrigo R Catharino
Zika virus (ZIKV) infection has recently emerged as a major concern worldwide due to its strong association with nervous system malformation (microcephaly) of fetuses in pregnant women infected by the virus. Signs and symptoms of ZIKV infection are often mistaken with other common viral infections. Since transmission may occur through biological fluids exchange and coitus, in addition to mosquito bite, this condition is an important infectious disease. Thus, understanding the mechanism of viral infection has become an important research focus, as well as providing potential targets for assertive clinical diagnosis and quality screening for hemoderivatives...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29063982/role-of-beta-adrenergic-receptors-and-sirtuin-signaling-in-the-heart-during-aging-heart-failure-and-adaptation-to-stress
#16
REVIEW
Regina Celia Spadari, Claudia Cavadas, Ana Elisa T Saturi de Carvalho, Daniela Ortolani, Andre Luiz de Moura, Paula Frizera Vassalo
In the heart, catecholamine effects occur by activation of beta-adrenergic receptors (β-ARs), mainly the beta 1 (β1-AR) and beta 2 (β2-AR) subtypes, both of which couple to the Gs protein that activates the adenylyl cyclase signaling pathway. The β2-ARs can also couple to the Gi protein that counterbalances the effect of the Gs protein on cyclic adenosine monophosphate production and activates the phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway. In several cardiovascular disorders, including heart failure, as well as in aging and in animal models of environmental stress, a reduction in the β1/β2-AR ratio and activation of the β2-AR-Gi-PI3K-Akt signaling pathway have been observed...
October 24, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/29056532/lamp3-regulates-hepatic-lipid-metabolism-through-activating-pi3k-akt-pathway
#17
Xiaoyu Liao, Lingyu Song, Linlin Zhang, Hui Wang, Qiang Tong, Jing Xu, Gangyi Yang, Shiming Yang, Hongting Zheng
Lysosome associated membrane protein 3 (LAMP3), a highly glycosylated protein, is one member of the LAMPs family. LAMPs family plays a critical role in the autolysosome fusion process. Autophagy was recently confirmed to regulate hepatic lipolysis. However, the physiological function of LAMP3 in lipid metabolism is not clear. In the current study, we discovered that the LAMP3 expression level was higher in the liver tissues of non-alcoholic fatty liver disease (NAFLD) patients and high-fat diet and ob/ob mice than in the matched control groups...
October 19, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29054015/synergistic-effect-of-copper-and-arsenic-upon-oxidative-stress-inflammation-and-autophagy-alterations-in-brain-tissues-of-gallus-gallus
#18
Xiao Sun, Jinglun Li, Hongjing Zhao, Yu Wang, Juanjuan Liu, Yizhi Shao, Yuan Xue, Mingwei Xing
Arsenic or copper is one of the most highly toxic pollution that can cause dysfunction to brains, however, the exact mechanism remains unclear. The aim of the study is to investigate the mechanisms of arsenic or/and copper-induced oxidative stress, inflammation and autophagy in chicken brains and elucidate the interactions between arsenic and copper. A total of 72 1-day-old Hy-line chickens were divided into four groups (18 chickens per group) treated with 30mg/kg arsenic trioxide (As2O3) or/and 300mg/kg copper sulfate (CuSO4) for 12weeks...
October 12, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/29052399/-effect-of-total-flavonoids-in-scutellaria-barbata-in-mediating-autophagy-in-tumor-cells-via-pi3k-akt-mtor-pathway
#19
Ming Chen, Ju-Tao Wang, Zhen-Ni Wu, Man-Yan Hu, Hua-Wu Gao
To investigate the effect of the total flavonoids in Scutellaria barbata(TF-SB) against autophagy in tumor cells in vivo, and further determine whether the mechanism is correlated with the PI3K/AKT/mTOR pathway, which lead to autophagy-induced tumor cell death. Melanoma-bearing mice were prepared and divided into control group, rapamycin group (Rap 1.5 mg•kg⁻¹), and high, middle and low-dose TF-SB (200, 100, 50 mg•kg⁻¹) groups. The groups were given drugs once a day for successively 11 days. The inhibitory effect of TF-SB on the growth of melanoma was determined by measuring tumor volume and tumor inhibition rate...
April 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29045477/tubastatin-ameliorates-pulmonary-fibrosis-by-targeting-the-tgf%C3%AE-pi3k-akt-pathway
#20
Shigeki Saito, Yan Zhuang, Bin Shan, Svitlana Danchuk, Fayong Luo, Martina Korfei, Andreas Guenther, Joseph A Lasky
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal disease. Histone deacetylase 6 (HDAC6) alters function and fate of various proteins via deacetylation of lysine residues, and is implicated in TGF-β1-induced EMT (epithelial-mesenchymal transition). However, the role of HDAC6 in pulmonary fibrosis is unknown. METHODS: HDAC6 expression in IPF and control lungs was assessed by quantitative real-time PCR (qRT-PCR) and immunoblots. Lung fibroblasts were treated with TGF-β1 ± HDAC6 inhibitors (Tubacin, Tubastatin, ACY1215, or MC1568), and fibrotic markers such as type I collagen were assessed using qRT-PCR and immunoblots...
2017: PloS One
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