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Autophagy and PI3K-Akt

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https://www.readbyqxmd.com/read/29775658/hydroxysafflor-yellow-a-protects-brain-microvascular-endothelial-cells-against-oxygen-glucose-deprivation-reoxygenation-injury-involvement-of-inhibiting-autophagy-via-class-i-pi3k-akt-mtor-signaling-pathway
#1
Guang Yang, Ning Wang, Sai Wang Seto, Dennis Chang, Huazheng Liang
The present study aimed to test whether Hydroxysafflor yellow A (HSYA) protects the brain microvascular endothelial cells (BMECs) injury induced by oxygen glucose deprivation/reoxygenation (OGD/R) via the PI3K/Akt/mTOR autophagy signaling pathway. Primary rat BMECs were cultured and identified by the expression of factor VIII-related antigen before being exposed to OGD/R to imitate ischemia/reperfusion (I/R) damage in vitro. The protective effect of HSYA was evaluated by assessing (1) cellular morphologic and ultrastructural changes; (2) cell viability and cytotoxicity; (3) transendothelial electrical resistance (TEER) of monolayer BMECs; (4) cell apoptosis; (5) fluorescence intensity of LC3B; (6) LC3 mRNA expression; (7) protein expressions of LC3, Beclin-1, Zonula occludens-1 (ZO-1), phospho-Akt (p-Akt), Akt, phospho-mTOR (p-mTOR) and mTOR...
May 15, 2018: Brain Research Bulletin
https://www.readbyqxmd.com/read/29760379/autophagic-degradation-of-caveolin-1-promotes-liver-sinusoidal-endothelial-cells-defenestration
#2
Xiaoying Luo, Dan Wang, Xintao Zhu, Guozhen Wang, Yuehua You, Zuowei Ning, Yang Li, Siyi Jin, Yun Huang, Ye Hu, Tingting Chen, Ying Meng, Xu Li
Autophagy, interacting with actin cytoskeleton and the NO-dependent pathway, may affect the phenotype and function of endothelial cells. Moreover, caveolin-1 (Cav-1), as a structure protein in liver sinusoidal endothelial cells (LSECs), is closely related to autophagy. Hence, we aim to explore the role of autophagic degradation of Cav-1 in LSECs defenestration. In vivo, we found the increase of autophagy in liver sinusoidal endothelium in human fibrotic liver. Furthermore, autophagy, degradation of Cav-1, and actin filament (F-actin) remodeling were triggered during the process of CCl4-induced LSECs defenestration; in contrast, autophagy inhibitor 3MA diminished the degradation of Cav-1 to maintain fenestrae and relieve CCl4-induced fibrosis...
May 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29752339/resveratrol-enhances-matrix-biosynthesis-of-nucleus-pulposus-cells-through-activating-autophagy-via-the-pi3k-akt-pathway-under-oxidative-damage
#3
Jinlou Gao, Qingyun Zhang, Lin Song
BACKGROUND: The decrease in nucleus pulposus (NP) matrix production is a classic  feature during disc degeneration. Resveratrol (RSV) is reported to play protective effects under many pathological factors. OBJECTIVE: This study aims to study the effects of RSV on NP matrix homeostasis under oxidative damage and the potential mechanism. METHODS: Rat NP cells were exposed to H2 O2 solution to create an oxidative damage. RSV and the 3‑Methyladenine (3-MA) was added along with the culture medium to respectively investigate the role of RSV and cellular autophagy...
May 11, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29743447/hydrogen-sulfide-ameliorates-rat-myocardial-fibrosis-induced-by-thyroxine-through-pi3k-akt-signaling-pathway
#4
Maojun Liu, Zining Li, Biao Liang, Ling Li, Shengquan Liu, Wenting Tan, Junrong Long, Fen Tang, Chun Chu, Jun Yang
This study aims to investigate the role and regulatory mechanism of the Hydrogen sulfide (H2 S) in amelioration of rat myocardial fibrosis induced by thyroxine through interfering the autophagy via regulating the activity of PI3K/AKT1 signaling pathway and the expression of relative miRNA. 40 adult male SD rats were randomly divided into 4 groups (n = 10): the control group, the thyroxine model group (TH group), the model group with H2 S intervention (TH + H2 S group) and the normal group with H2 S intervention (H2 S group)...
May 9, 2018: Endocrine Journal
https://www.readbyqxmd.com/read/29740349/severe-burn-induced-intestinal-epithelial-barrier-dysfunction-is-associated-with-endoplasmic-reticulum-stress-and-autophagy-in-mice
#5
Yalan Huang, Yanhai Feng, Yu Wang, Pei Wang, Fengjun Wang, Hui Ren
The disruption of intestinal barrier plays a vital role in the pathophysiological changes after severe burn injury, however, the underlying mechanisms are poorly understood. Severe burn causes the disruption of intestinal tight junction (TJ) barrier. Previous studies have shown that endoplasmic reticulum (ER) stress and autophagy are closely associated with the impairment of intestinal mucosa. Thus, we hypothesize that ER stress and autophagy are likely involved in burn injury-induced intestinal epithelial barrier dysfunction...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29734265/vaspin-prevents-tumor-necrosis-factor-%C3%AE-induced-apoptosis-in-cardiomyocytes-by-promoting-autophagy
#6
Xuan Ke, Yanqin Hao, Bingong Li, Jin Zou, Xuelian Li, Chunying Wei, Fuyou Liu, Zhiyong Zhang
Visceral adipose tissue-derived serine protease inhibitor (Vaspin) is an adipocytokine that has been shown to exert anti-inflammatory effects and inhibits apoptosis under diabetic conditions. This study was designed to investigate the impact of vaspin on autophagy in tumor necrosis factor (TNF)-α-induced injury in cardiomyocytes and its cardioprotective effects in the pathogenesis of diabetic cardiomyopathy (DCM). H9C2 cells were treated with TNF-α with or without vaspin in vitro. Tumor necrosis factor-α treatment inhibited autophagy and promoted apoptosis in H9C2 cells after stimulating for 24 hours...
May 2018: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/29731854/cantharidin-suppresses-cell-growth-and-migration-and-activates-autophagy-in-human-non-small-cell-lung-cancer-cells
#7
Yan-Peng Liu, Ling Li, Liang Xu, E-Nuo Dai, Wei-Da Chen
Cantharidin (CTD), a component of Mylabris (blister beetle), is a traditional Chinese medicine that exerts an anticancer effect in multiple types of cancer cells. The aim of the present study was to investigate whether CTD exhibited anti-metastatic and inhibitory cell proliferation effects against human non-small cell lung cancer (NSCLC) A549 cells, and the possible underlying mechanism by which this occurs. The results of the present study demonstrated that CTD arrested proliferation, suppressed invasion and migration and induced apoptosis in A549 cells in vitro ...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29724195/bioactive-components-and-mechanisms-of-chinese-poplar-propolis-alleviates-oxidized-low-density-lipoprotein-induced-endothelial-cells-injury
#8
Huasong Chang, Wenwen Yuan, Haizhu Wu, Xusheng Yin, Hongzhuan Xuan
BACKGROUND: Propolis, a polyphenol-rich natural product, has been used as a functional food in anti-inflammation. However, its bioactive components and mechanisms have not been fully elucidated. To discover the bioactive components and anti-inflammatory mechanism, we prepared and separated 8 subfractions from ethyl acetate extract of Chinese propolis (EACP) and investigated the mechanism in oxidized low density lipoprotein (ox-LDL) induced human umbilical vein endothelial cells (HUVECs) damage...
May 3, 2018: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29710540/effects-of-artesunate-on-chondrocyte-proliferation-apoptosis-and-autophagy-through-the-pi3k-akt-mtor-signaling-pathway-in-rat-models-with-rheumatoid-arthritis
#9
Fa-Bo Feng, Hai-Yan Qiu
BACKGROUND: Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily results in warm, swollen, and painful joints. In this study, we investigate the potentially therapeutic role of artesunate (Art) on chondrocyte proliferation, apoptosis and autophagy in rheumatoid arthritis (RA) via the PI3K/AKT/mTOR signaling pathway. METHODS: Rat model of RA was successfully established through subcutaneous injection of emulsion. Positive protein expression rates of PI3K, AKT and mTOR were determined by immunohistochemistry...
April 7, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29705899/interplay-between-elemental-imbalance-related-pi3k-akt-mtor-regulated-apoptosis-and-autophagy-in-arsenic-iii-induced-jejunum-toxicity-of-chicken
#10
Yu Wang, Hongjing Zhao, Yizhi Shao, Juanjuan Liu, Jinglun Li, Mingwei Xing
Arsenic trioxide (As2 O3 ), the most toxic form of arsenic found in foodstuffs, is considered a carcinogen for human and animal. But many of the events that occur during its passage through the gastrointestinal tract are uncharted in birds. This study assesses the toxic effect on the jejunum of chicken which subchronically exposed to diets that contain As2 O3 (0, 0.625, 1.25, 2.5 mg/kg body weight) for 90 days. Electron microscopy, TdT-mediated dUTP nick-end labeling (TUNEL), qPCR, and Western blot were performed...
April 28, 2018: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29705604/bone-marrow-mesenchymal-stem-cells-conditioned-medium-protects-vsc4-1-cells-against-2-5-hexanedione-induced-autophagy-via-ngf-pi3k-akt-mtor-signaling-pathway
#11
Xin Zhang, Ying Kong, Yijie Sun, Zhiqiang Qian, Chenxue Gao, Xiaoxia Shi, Shuangyue Li, Yongjun Piao, Fengyuan Piao
We aimed to investigate the effects of bone marrow mesenchymal stem cell conditioned medium (BMSC-CM) in preventing 2,5-hexanedione (HD)-induced damage to motoneurons, and examined the molecular mechanisms that mediate these effects. VSC4.1 cells were exposed to 25 mM HD for 24 h followed by incubation with DMEM for 24 h. HD-treated cells were incubated with BMSC-CM at varied concentrations. Incubation with BMSC-CM ameliorated the decreased cell viability and reduced LDH release from cells exposed to HD. BMSC-CM suppressed the elevated number of autophagic vacuoles, cells with LC3 puncta, increased LC3-II/LC3-I ratio, and decreased p62 caused by HD exposure...
April 26, 2018: Brain Research
https://www.readbyqxmd.com/read/29692710/pp242-counteracts-glioblastoma-cell-proliferation-migration-invasiveness-and-stemness-properties-by-inhibiting-mtorc2-akt
#12
Carmen Mecca, Ileana Giambanco, Stefano Bruscoli, Oxana Bereshchenko, Bernard Fioretti, Carlo Riccardi, Rosario Donato, Cataldo Arcuri
Glioblastoma multiforme (GBM) is the most malignant brain tumor and is associated with poor prognosis due to its thorny localization, lack of efficacious therapies and complex biology. Among the numerous pathways driving GBM biology studied so far, PTEN/phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) signaling plays a pivotal role, as it controls cell survival, proliferation and metabolism and is involved in stem cell maintenance. In front of recent and numerous evidences highlighting mTOR upregulation in GBM, all the strategies developed to inhibit this pathway have been substantially unsuccessful...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29680738/inhibition-of-pi3k-akt-mtor-pathway-by-apigenin-induces-apoptosis-and-autophagy-in-hepatocellular-carcinoma-cells
#13
Jiali Yang, Cuicui Pi, Guanghui Wang
Apigenin is a dietary flavonoid with known antioxidant and antitumor effects against several types of cancers by promoting cell death and inducing cell cycle arrest. Apigenin also regulates a variety of intracellular signal transduction pathways during apoptosis or autophagy. However, the precise mechanism underlying the anticancer effects of apigenin in liver cancer remains poorly understood. In this study, we demonstrated that apigenin has anticancer activity against hepatocellular carcinoma cells. Apigenin inhibited the cell growth and induced cell death in a dose- and time-dependent manner in HepG2 cells...
April 19, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29673591/long-noncoding-rna-haglros-regulates-cell-apoptosis-and-autophagy-in-lipopolysaccharides-induced-wi-38-cells-via-modulating-mir-100-nf-%C3%AE%C2%BAb-axis
#14
Meihan Liu, Tao Han, Shaomin Shi, Enqi Chen
Pneumonia is a lower respiratory disease caused by pathogens or other factors. This study aimed to explore the roles and mechanism of long noncoding RNA HAGLROS in lipopolysaccharides (LPS)-induced inflammatory injury in pneumonia. The HAGLROS expression in serum of patients with acute stage pneumonia was detected. To induce pulmonary injury, WI-38 human lung fibroblasts were stimulated with lipopolysaccharides (LPS). The HAGLROS expressions in LPS-treated WI-38 cells and the effects of HAGLROS knockdown on the viability, apoptosis, and autophagy of LPS-induced cells were detected...
April 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29658606/chloroquine-inhibits-cell-growth-in-human-a549-lung-cancer-cells-by-blocking-autophagy-and-inducing-mitochondrial%C3%A2-mediated-apoptosis
#15
Likun Liu, Cuicui Han, Haitao Yu, Wenbin Zhu, Hongxia Cui, Lihong Zheng, Chunjing Zhang, Liling Yue
Chloroquine (CQ) has been revealed to exhibit antitumor activity in several human tumors including lung cancer as mono‑ or add‑on therapy. The antitumor effect of CQ appears to depend on the tumor type, stage and genetic context. Few studies have focused on the mechanism concerning the antitumor effect of CQ monotherapy and the cause and effect relationship among autophagy, apoptosis and CQ in human lung A549 cells. Therefore, the present study aimed to identify the antitumor effect of CQ monotherapy and analyze the possible mechanism...
April 12, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29651246/lactone-component-from-ligusticum-chuanxiong-alleviates-myocardial-ischemia-injury-through-inhibiting-autophagy
#16
Gang Wang, Guoliang Dai, Jie Song, Maomao Zhu, Ying Liu, Xuefeng Hou, Zhongcheng Ke, Yuanli Zhou, Huihui Qiu, Fujing Wang, Nan Jiang, Xiaobin Jia, Liang Feng
The dysregulation of autophagy is associated with a series of cardiovascular diseases, such as myocardial ischemia injury. Lactone component from Ligusticum chuanxiong (LLC) is the major constituent of the traditional Chinese herb L. chuanxiong Hort., which has been reported to hold potential cardioprotective effects. In this study, to determine whether LLC protects the heart through regulation of autophagy, we explored the effects of LLC on cardioprotection and autophagy in myocardial ischemia injured rats and H9c2 cardiomyocytes...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29625382/phthalimide-conjugations-for-the-degradation-of-oncogenic-pi3k
#17
Wenlu Li, Chunmei Gao, Lei Zhao, Zigao Yuan, Yuzong Chen, Yuyang Jiang
PI3K/Akt/mTOR pathway is crucial for carcinogenesis and its inhibitors have made a great progress in cancer treatment. However, there is still a great developing space for PI3K inhibitors as the acquired drug resistance hindered their application in clinical. Proteolysis-targeting chimeras (PROTACs) with the potential to handle the challenges faced in drug development could be an alternative therapeutic strategy. Moreover, the past two years have witnessed remarkable advances in the development of phthalimide conjugation as a strategy for the degradation instead of inhibition of the targets, including BET family proteins, Sirtuin 2, CDK 9, Smad 3, and BCR-ABL proteins...
March 26, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29620275/effects-of-endoplasmic-reticulum-stress-on-autophagy-and-apoptosis-of-human-leukemia-cells-via-inhibition-of-the-pi3k-akt-mtor-signaling-pathway
#18
Li-Juan Li, Ye Chai, Xiao-Jia Guo, Song-Lin Chu, Lian-Sheng Zhang
The present study aimed to explore the regulatory effects of endoplasmic reticulum stress (ERS) on the phosphoinositide 3‑kinase (PI3K)/AKT serine/threonine kinase 1 (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, and its subsequent effects on autophagy and apoptosis of human leukemia cells. Human leukemia cells were cultured and treated with various concentrations of tunicamycin for 0, 24, 48, 72 and 90 h. Subsequently, human leukemia cells were assigned into the ER activation group, which was treated with 100 ng/ml tunicamycin, the ER activation + TO901317 (PI3K inhibitor) group, and the control group...
April 3, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29620175/egfr%C3%A2-associated-pathways-involved-in-traditional-chinese-medicine-tcm-%C3%A2-1%C3%A2-induced-cell-growth-inhibition-autophagy-and-apoptosis-in-prostate-cancer
#19
Zhaomeng Wu, Qingyi Zhu, Yu Zhang, Yingying Yin, Dan Kang, Runyi Cao, Qian Tian, Shan Lu, Ping Liu
Traditional Chinese medicine (TCM) has the synergistic effect of the combination of a single ingredient and a monomer, and systemic and local therapeutic effects in cancer treatment, through which TCM is able to enhance the curative effect and reduce the side effects. The present study analyzed the effect of TCM‑1 (an anti‑cancer TCM) on prostate cancer (PCa) cell lines, and studied in detail the mechanism of cell death induced by TCM‑1 in vitro and in vivo. From the present results, it was identified for the first time, to the best of our knowledge, that TCM‑1 arrested the cell cycle at the G1 phase, decreased cell viability and increased nuclear rupture in a dose‑dependent manner; these effects finally resulted in apoptosis in PCa cells...
March 28, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29620171/tripterygium-glycoside-protects-against-puromycin-amino-nucleoside%C3%A2-induced-podocyte-injury-by-upregulating-autophagy
#20
Jianguang Gong, Juan Jin, Li Zhao, Yiqiao Li, Yiwen Li, Qiang He
Tripterygium glycoside (TG), an active ingredient of the widely used Chinese herb Tripterygium wilfordii Hook F, has immunosuppressive and anti‑inflammatory effects. Previous studies have indicated that TG is a potentially effective therapeutic option to treat nephrotic syndrome. The mechanism underlying the therapeutic effect of TG, including its effect on autophagy and apoptosis in podocyte injury, remains to be fully elucidated. The present study aimed to assess the protective effect of TG on podocytes via its potential role in the activation of autophagic and phosphatidylinositol 3‑kinase (PI3K) pathways...
March 29, 2018: International Journal of Molecular Medicine
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