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Beclin-1

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https://www.readbyqxmd.com/read/28806762/a-becn1-mutation-mediates-hyperactive-autophagic-sequestration-of-amyloid-oligomers-and-improved-cognition-in-alzheimer-s-disease
#1
Altea Rocchi, Soh Yamamoto, Tabitha Ting, Yuying Fan, Katherine Sadleir, Yigang Wang, Weiran Zhang, Sui Huang, Beth Levine, Robert Vassar, Congcong He
Impairment of the autophagy pathway has been observed during the pathogenesis of Alzheimer's disease (AD), a neurodegenerative disorder characterized by abnormal deposition of extracellular and intracellular amyloid β (Aβ) peptides. Yet the role of autophagy in Aβ production and AD progression is complex. To study whether increased basal autophagy plays a beneficial role in Aβ clearance and cognitive improvement, we developed a novel genetic model to hyperactivate autophagy in vivo. We found that knock-in of a point mutation F121A in the essential autophagy gene Beclin 1/Becn1 in mice significantly reduces the interaction of BECN1 with its inhibitor BCL2, and thus leads to constitutively active autophagy even under non-autophagy-inducing conditions in multiple tissues, including brain...
August 14, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28804535/hongjingtian-injection-attenuates-myocardial-oxidative-damage-via-promoting-autophagy-and-inhibiting-apoptosis
#2
Shujing Zhang, Ling Zhang, Han Zhang, Guanwei Fan, Jiuwen Qiu, Zongbao Fang, Haibo Wu, Yi Wang, Xiaoping Zhao
Natural products with antioxidative activities are widely applied to prevent and treat various oxidative stress related diseases, including ischemic heart disease. However, the cellular and molecular mechanisms of those therapies are still needed to be illustrated. In this study, we characterized the cardioprotective effects of Hongjingtian Injection (HJT), an extensively used botanical drug for treating coronary heart disease. The H/R-induced profound elevation of oxidative stress was suppressed by HJT. HJT also attenuates oxidative injury by promoting cell viability, intracellular ATP contents, and mitochondrial oxygen consumption...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28803810/autophagy-plays-a-positive-role-in-zinc-induced-apoptosis-in-intestinal-porcine-epithelial-cells
#3
Xin Zhou, Yansen Li, ChunMei Li
A high‑zinc (Zn) diet has been found to promote growth performance in pigs, but causes cell apoptosis in the intestinal epithelium. To investigate the mechanism underlying the high dietary Zn-induced apoptosis in porcine small intestinal epithelium, IPEC-J2 cells (intestinal porcine epithelial cells) were used to determine the effect of Zn on cell inhibitory, apoptosis, and mitochondrial membrane potential and autophagy in vitro. Results showed that Zn inhibited IPEC-J2 cell proliferation and induced apoptosis and autophagy...
August 10, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28802099/cancer-associated-fibroblasts-autophagy-enhances-progression-of-triple-negative-breast-cancer-cells
#4
Mengchuan Wang, Jian Zhang, Yizhe Huang, Shufeng Ji, Guoli Shao, Shaobo Feng, Danxun Chen, Kankan Zhao, Zixiang Wang, Aiguo Wu
BACKGROUND Cancer-associated fibroblasts (CAFs) are key factors in malignant tumor initiation, progression, and metastasis. However, the effect of CAFs autophagy on triple-negative breast cancer (TNBC) cells is not clear. In this study, the growth effect of TNBC cells regulated by CAFs autophagy was evaluated. MATERIAL AND METHODS CAFs were obtained from invasive TNBC tumors and identified by Western blot and immunofluorescence staining assay. CAFs were co-cultured with TNBC cells, and migration and invasion were evaluated by Matrigel-coated Transwell and Transwell inserts...
August 12, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28800676/development-and-evaluation-of-heartbeat-a-machine-perfusion-heart-preservation-system
#5
Yongnan Li, Qingdong Zeng, Gang Liu, Junzhe Du, Bingren Gao, Wei Wang, Zhe Zheng, Shengshou Hu, Bingyang Ji
Static cold storage is accompanied with a partial safe ischemic interval for donor hearts. In this current study, a machine perfusion system was built to provide a better preservation for the donor heart and assessment for myocardial function. Chinese mini-swine (weight 30-35 kg, n = 16) were randomly divided into HTK, Celsior, and Heartbeat groups. All donor hearts were respectively preserved for 8 hours under static cold storage or machine perfusion. The perfusion solution is aimed to maintain its homeostasis based on monitoring the Heartbeat group...
August 11, 2017: Artificial Organs
https://www.readbyqxmd.com/read/28800456/synthesis-and-anticancer-properties-of-ruthenium-ii-complexes-as-potent-apoptosis-inducers-through-mitochondrial-disruption
#6
Dan Wan, Bing Tang, Yang-Jie Wang, Bo-Hong Guo, Hui Yin, Qiao-Yan Yi, Yun-Jun Liu
A new ligand MHPIP (MHPIP = 2-(1-methyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-f][1,10]phenanthroline) and its three ruthenium (II) complexes [Ru(N-N)2(MHPIP)](ClO4)2 (N-N = phen: 1,10-phenanthroline 1; dmp = 2,9-dimethyl-1,10-phenanthroline 2; ttbpy = 4,4'-ditertiarybutyl-2,2'-bipyridine 3) were synthesized and characterized. The cytotoxic activity in vitro was studied by MTT method. The complexes 1-3 show moderate cytotoxic effects on the cell growth in HepG2 cells with an IC50 value of 25.5 ± 3.5, 35...
July 28, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28798804/sinomenine-hydrochloride-attenuates-renal-fibrosis-by-inhibiting-excessive-autophagy-induced-by-adriamycin-an-experimental-study
#7
Ming-Ming Zhao, Bin Yang, Qiu Zhang, Jin-Hu Wang, Jin-Ning Zhao, Yu Zhang
The objective of this study is to investigate if sinomenine hydrochloride (SIN-HCl) could be effective against adriamycin-induced renal fibrosis by regulating autophagy in a rat model. Forty male Sprague-Dawley (SD) rats were randomly divided into control group, model group, telmisartan group, and SIN-HCl group; rat model was induced by adriamycin; all rats were given intragastric administration for 6 weeks. Urine was collected from rats in metabolic cages to determine 24 h protein level. This was done after intragastric administration for the first two weeks and then once for every two weeks...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28798234/structural-transitions-in-conserved-ordered-beclin-1-domains-essential-to-regulating-autophagy
#8
Karen Glover, Yue Li, Shreya Mukhopadhyay, Zoe Leuthner, Srinivas Chakravarthy, Christopher L Colbert, Sangita C Sinha
Beclin 1 (BECN1) is a key regulator of autophagy, a critical catabolic homeostasis pathway that involves the sequestration of cytoplasmic components by multilayered vesicles called autophagosomes, followed by lysosomal fusion and degradation. BECN1 is a core component of class III phosphatidylinositol-3-kinase complexes responsible for autophagosome nucleation. Without heterologous binding partners, BECN1 forms an antiparallel homodimer via its coiled-coil domain (CCD). However, the last 16 CCD residues, composing an overlap helix (OH), have been crystallized in two mutually exclusive states: either as part of the CCD or packed against the C-terminal lower case β-α-repeated, autophagy-specific domain (BARAD)...
August 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28790887/mir-16-and-fluoxetine-both-reverse-autophagic-and-apoptotic-change-in-chronic-unpredictable-mild-stress-model-rats
#9
Yang Yang, Zhiying Hu, Xiaoxue Du, Henry Davies, Xue Huo, Marong Fang
In the clinic selective serotonin reuptake inhibitors (SSRIs), like Fluoxetine, remain the primary treatment for major depression. It has been suggested that miR-16 regulates serotonin transporters (SERT) via raphe nuclei and hippocampal responses to antidepressants. However, the underlying mechanism and regulatory pathways are still obtuse. Here, a chronic unpredicted mild stress (CUMS) depression model in rats was established, and then raphe nuclei miR-16 and intragastric Fluoxetine injections were administered for a duration of 3 weeks...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28782635/withaferin-a-induced-impaired-autophagy-and-unfolded-protein-response-in-human-breast-cancer-cell-lines-mcf-7-and-mda-mb-231
#10
Kamalini Ghosh, Soumasree De, Srimoyee Mukherjee, Sayantani Das, Amar Nath Ghosh, Sumita Bandyopadhyay Sengupta
The autophagy-lysosome pathway and the ubiquitin-proteasome systems are the two major routes for eukaryotic intracellular protein clearance. Cancerous cells often display elevated protein synthesis and byproduct disposal, thus, inhibition of the protein degradation pathways became an emerging approach for cancer therapy. The present study revealed that withaferin-A (WA), the biologically active withanolide derived from Withania somnifera, initially induced formation of autophagosomes in human breast cancer cell-lines, MCF-7 and MDA-MB-231...
August 3, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28779993/the-class-i-pi3k-inhibitor-s14161-induces-autophagy-in-malignant-blood-cells-by-modulating-the-beclin-1-vps34-complex
#11
Siyu Wang, Jie Li, Yanyun Du, Yujia Xu, Yali Wang, Zubin Zhang, Zhuan Xu, Yuanying Zeng, Xinliang Mao, Biyin Cao
S14161 is a pan-Class I PI3K inhibitor that induces blood cancer cell death, but its mechanism is largely unknown. In the present study, we evaluated the role of S14161 in autophagy, an emerging event in cell destination. Multiple myeloma cell lines RPMI-8226, OPM2, KMS11 and leukemia cell line K562 were treated with S14161. The results showed that S14161 induced autophagy as demonstrated by increased LC3-II and decreased p62, which were prevented by autophagy inhibitors including 3-methyladenine and bafilomycin A1...
July 19, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28776671/%C3%AE-asarone-inhibited-cell-growth-and-promoted-autophagy-via-p53-bcl-2-bclin-1-and-p53-ampk-mtor-pathways-in-human-glioma-u251-cells
#12
Nanbu Wang, Qinxin Zhang, Laiyu Luo, Baile Ning, Yongqi Fang
Glioma is the most common type of primary brain tumor and has an undesirable prognosis. Autophagy plays an important role in cancer therapy, but it's effect is still not definite. P53 is an important tumor suppressor gene and protein that is closely to autophagy. Our aim was to study the effect of β-asarone on inhibiting cell proliferation in human glioma U251 cells and to detect the effect of the inhibition on autophagy through the P53 signal pathway. For cell growth, the cells were divided into four groups: the model, β-asarone, temozolomide (TMZ) and co-administration groups...
August 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28767174/inactivation-of-beclin-1-dependent-autophagy-promotes-ursolic-acid-induced-apoptosis-in-hypertrophic-scar-fibroblasts
#13
Chuan Cao, Wenping Wang, Lele Lu, Liang Wang, XiaoSong Chen, Rui Guo, Shirong Li, Junzi Jiang
A hypertrophic scar (HS) is caused by abnormal proliferation of dermal fibroblasts. Thus, promoting hypertrophic scar fibroblast (HSFB) apoptosis is an effective strategy for HS therapy. Ursolic acid (UA) has been widely used as an inducer of apoptosis in diverse cancers. However, whether UA plays an inhibitory role in HS formation is still unknown. In our study, UA was used to treat HSFBs and the cell viability, apoptosis, and collagen synthesis were determined by a Cell Counting Kit 8 (CCK8) assay, flow cytometry, and an H(3) -proline incorporation assay, respectively...
August 2, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28765693/jianpi-qingchang-decoction-regulates-intestinal-motility-of-dextran-sulfate-sodium-induced-colitis-through-reducing-autophagy-of-interstitial-cells-of-cajal
#14
Yan-Cheng Dai, Lie Zheng, Ya-Li Zhang, Xuan Chen, De-Liang Chen, Li-Juan Wang, Zhi-Peng Tang
AIM: To investigate the underlying effect of Jianpi Qingchang decoction (JQD) regulating intestinal motility of dextran sulfate sodium (DSS)-induced colitis in mice. METHODS: C57BL/6 mice were randomly divided into four groups: the control group, the DSS group, the JQD group, and the 5-aminosalicylic acid group. Except for the control group, colitis was induced in other groups by giving distilled water containing 5% DSS. Seven days after modeling, the mice were administered corresponding drugs intragastrically...
July 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28760906/mechanisms-of-action-of-vitamin-d-as-supplemental-therapy-for-pneumocystis-pneumonia
#15
Guang-Sheng Lei, Chen Zhang, Bi-Hua Cheng, Chao-Hung Lee
The combination of trimethoprim and sulfamethoxazole (TMP-SMX) is the most effective regimen for therapy of Pneumocystis pneumonia (PcP). As many patients with PcP are allergic or do not respond to it, efforts have been devoted to develop alternative therapies for PcP. We have found that the combination of vitamin D3 (VitD3; 300 IU/kg/day) and PMQ (5 mg/kg/day) was as effective as TMP-SMX for therapy of PcP. In this study, we investigated the mechanisms by which vitamin D enhances the efficacy of PMQ. C57BL/6 mice were immunosuppressed by CD4(+) cell depletion, infected with P...
July 31, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28760737/docetaxel-reverses-pulmonary-vascular-remodeling-by-decreasing-autophagy-and-resolves-right-ventricular-fibrosis
#16
Yasmine F Ibrahim, Nataliia V Shults, Vladyslava Rybka, Yuichiro J Suzuki
Pulmonary arterial hypertension remains a fatal disease despite the availability of approved vasodilators. Since vascular remodeling contributes to increased pulmonary arterial pressure, new agents that reduce the thickness of pulmonary vascular walls have therapeutic potential. Thus, anti-tumor agents that are capable of killing cells were investigated. Testing of various anti-tumor drugs identified that docetaxel is a superior drug for killing proliferating pulmonary artery smooth muscle cells compared with other drugs including gemcitabine, methotrexate and ifosfamide...
July 31, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28759157/mtor-notch3-signaling-mediates-pulmonary-hypertension-in-hypoxia-exposed-neonatal-rats-independent-of-changes-in-autophagy
#17
Julijana Ivanovska, Sparsh Shah, Mathew J Wong, Crystal Kantores, Amish Jain, Martin Post, Behzad Yeganeh, Robert P Jankov
BACKGROUND/AIM: Mammalian target of rapamycin (mTOR) is a pivotal regulator of cell proliferation, survival, and autophagy. Autophagy is increased in adult experimental chronic pulmonary hypertension (PHT), but its contributory role to pulmonary vascular disease remains uncertain and has yet to be explored in the neonatal animal. Notch is a major pro-proliferative pathway activated by mTOR. A direct relationship between autophagy and Notch signaling has not been previously explored. Our aim was to examine changes in mTOR-, Notch-, and autophagy-related pathways and the therapeutic effects of autophagy modulators in experimental chronic neonatal PHT secondary to chronic hypoxia...
July 31, 2017: Pediatric Pulmonology
https://www.readbyqxmd.com/read/28749469/zinc-oxide-nanoparticles-harness-autophagy-to-induce-cell-death-in-lung-epithelial-cells
#18
Jun Zhang, Xia Qin, Bin Wang, Ge Xu, Zhexue Qin, Jian Wang, Lanxiang Wu, Xiangwu Ju, Diptiman D Bose, Feng Qiu, Honghao Zhou, Zhen Zou
Although zinc oxide nanoparticles (ZnONPs) are widely used, they have raised concerns of toxicity in humans. Previous studies have indicated that reactive oxygen species (ROS) and autophagy are involved in the cytotoxicity of ZnONPs, but the regulatory mechanisms between autophagy and ROS remain to be elucidated. Herein, we comprehensively investigated the regulatory mechanism of autophagy and the link between autophagy and ROS in ZnONPs-treated lung epithelial cells. We demonstrated that ZnONPs could induce autophagy, and this process could enhance the dissolution of ZnONPs in lysosomes to release zinc ions...
July 27, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28748915/the-endoplasmic-reticulum-stress-autophagy-pathway-is-involved-in-apelin-13-induced-cardiomyocyte-hypertrophy-in-vitro
#19
Feng Xie, Di Wu, Shi-Fang Huang, Jian-Gang Cao, He-Ning Li, Lu He, Mei-Qing Liu, Lan-Fang Li, Lin-Xi Chen
Apelin is the endogenous ligand for the G protein-coupled receptor APJ, and plays important roles in the cardiovascular system. Our previous studies showed that apelin-13 promotes the hypertrophy of H9c2 rat cardiomyocytes through the PI3K-autophagy pathway. The aim of this study was to explore what roles ER stress and autophagy played in apelin-13-induced hypertrophy of cardiomyocytes in vitro. Treatment of H9c2 cells with apelin-13 (0.001-2 μmol/L) dose-dependently increased the production of ROS and the expression levels of NADPH oxidase 4 (NOX4)...
July 27, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28745544/euptox-a-induces-g1-arrest-and-autophagy-via-p38-mapk-and-pi3k-akt-mtor-mediated-pathways-in-mouse-splenocytes
#20
Quan Mo, Liwen Hu, Jiahua Weng, Yong Zhang, Yancheng Zhou, Ruiguang Xu, Zhicai Zuo, Junliang Deng, Zhihua Ren, Zhijun Zhong, Guangneng Peng, Xiang Nong, Yahui Wei, Yanchun Hu
Euptox A (9-oxo-10, 11-dehydroageraphorone), the main toxin isolated from Eupatorium adenophorum, is known to induce immunotoxicity in animals. However, the precise mechanism underlying the effects of Euptox A on splenocytes is unclear. Here, we aimed to investigate the molecular mechanisms underlying the effect of Euptox A in mouse spleens after its intragastric administration and found that Euptox A exhibits proautophagic effects in splenocytes. Euptox A markedly arrested the splenocytes in the G0/G1 phase, which was accompanied by inhibition of the expression of the positive regulators CDK4, CDK2, cyclin D1, PCNA, and E2F1, and promotion of the expression of the negative regulators p53, p21 Waf1/Cip1, p27 Kip1, and Chk1...
July 1, 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
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