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Autophagy

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https://www.readbyqxmd.com/read/29458150/pink1-protects-auditory-hair-cells-and-spiral-ganglion-neurons-from-cisplatin-induced-ototoxicity-via-inducing-autophagy-and-inhibiting-jnk-signaling-pathway
#1
Qianqian Yang, Gaoying Sun, Haiyan Yin, Hongrui Li, Zhixin Cao, Jinghan Wang, Meijuan Zhou, Haibo Wang, Jianfeng Li
Phosphatase and tensin homologue (PTEN)-induced putative kinase 1 (PINK1) gene encodes a serine/threonine kinase, which acts as a molecular sensor of mitochondrial health necessary for mitochondrial quality control. The present study was designed to examine whether PINK1 expressed in C57BL/6 murine cochlea and HEI-OC1 cells and, if so, to investigate the possible mechanisms underlying the action of PINK1 in cisplatin-induced death of sensory hair cells (HCs) and spiral ganglion neurons (SGNs) in vitro. The expression pattern of PINK1, formation of parkin particles, and autophagy were determined by immunofluorescent staining...
February 16, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29458142/insufficient-radiofrequency-ablation-promotes-proliferation-of-residual-hepatocellular-carcinoma-via-autophagy
#2
Zizhuo Zhao, Jiayi Wu, Xiaodi Liu, Ming Liang, Xinchuan Zhou, Shi Ouyang, Jiyi Yao, Jinquan Wang, Baoming Luo
Radiofrequency ablation (RFA) is considered to be a potentially curative therapy for hepatocellular carcinoma (HCC). However, insufficient RFA (IRFA) can promote rapid progression of the residual tumor. The mechanisms underlying IRFA-induced tumor promotion remain poorly understood. In the present study, we have established a subcutaneous xenograft mouse model and monitored the location and extent of IRFA by dual monitoring with ultrasonography and a thermal imager. For the first time, we provide evidence of the activation of autophagic pathways in mice exposed to IRFA...
February 16, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29458048/4-phenylbutyric-acid-protects-against-lipopolysaccharide-induced-bone-loss-by-modulating-autophagy-in-osteoclasts
#3
Hyun-Jung Park, Ho-Jung Son, Ok-Joo Sul, Jae-Hee Suh, Hye-Seon Choi
4-Phenylbutyric acid (4-PBA) has been used clinically to treat urea cycle disorders and is known to be an inhibitor of endoplasmic reticulum (ER) stress. We hypothesized that 4-PBA attenuates inflammatory bone loss by inducing autophagy, a process that is frequently accompanied by ER stress. Micro computerized tomography analysis showed that 4-PBA attenuated LPS-induced bone loss in mice. The increased area of TRAP-positive osteoclasts (OCs) and serum level of collagen type I fragments in lipopolysaccharide (LPS)-treated mice were also decreased when 4-PBA was administered, suggesting a protective role of 4-PBA in OCs...
February 16, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29457983/antimycobacterial-effect-of-ifng-interferon-gamma-induced-autophagy-is-dependent-on-the-hmox1-heme-oxygenase-1-mediated-increase-in-the-intracellular-calcium-levels-and-modulation-of-ppp3-calcineurin-tfeb-transcription-factor-eb-axis
#4
Nisha Singh, Pallavi Kansal, Zeeshan Ahmad, Naveen Baid, Hariom Kushwaha, Neeraj Khatri, Ashwani Kumar
IFNG (interferon gamma)-induced autophagy plays an important role in the elimination of intracellular pathogens, such as Mycobacterium tuberculosis (Mtb). However, the signaling cascade that leads to the increase in autophagy flux in response to IFNG is poorly defined. Here, we demonstrate that HMOX1 (heme oxygenase 1)-generated carbon monoxide (CO) is required for the induction of autophagy and killing of Mtb residing in macrophages in response to immunomodulation by IFNG. Interestingly, IFNG exposure of macrophages induces an increase in intracellular calcium levels that is dependent on HMOX1 generated CO...
February 19, 2018: Autophagy
https://www.readbyqxmd.com/read/29457968/in-vitro-and-in-vivo-effects-of-mk2206-and-chloroquine-combination-therapy-on-endometriosis-autophagy-may-be-required-for-regrowth-of-endometriosis
#5
Sachiko Matsuzaki, Jean-Luc Pouly, Michel Canis
BACKGROUND AND PURPOSE: A high recurrence rate after medical treatment is a major clinical problem for patients with endometriosis. In the present study, we evaluated the in vitro effects of combined treatment with MK2206 (an AKT inhibitor) + chloroquine on cell growth and regrowth of endometriotic stromal cells, and the in vivo effects on endometriotic implants in a mouse xenograft model of endometriosis. EXPERIMENTAL APPROACH: We evaluated the effects of autophagy inhibition by knockdown of the ATG13, Beclin-1, and ATG12 genes and pharmacologic agents (chloroquine, bafilomycin A1, or 3-methyalanine) individually and in combination with MK2206 on cell growth and/or cell regrowth of endometriotic stromal cells in vitro...
February 19, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29457374/proteasomal-function-is-impaired-in-human-osteoarthritic-chondrocytes-and-this-can-contribute-to-decreased-sox9-and-aggrecan
#6
Ramon L Serrano, Liang-Yu Chen, Martin K Lotz, Ru Liu-Bryan, Robert Terkeltaub
OBJECTIVE: Osteoarthritis (OA) chondrocytes have impaired autophagy, one arm of the proteostasis network that coordinates proteome and organelle quality control and degradation. Deficient proteostasis impacts differentiation and viability, and inflammatory processes in aging and disease. Studying OA chondrocytes, we assessed ubiquitin proteasome system proteasomal function. METHODS: We evaluated human knee cartilages by immunohistochemistry, and assessed proteasomal function, levels of proteasomal core subunits and chaperones, and autophagy in cultured chondrocytes...
February 18, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29457340/key-role-of-tfeb-nucleus-translocation-for-silver-nanoparticle-induced-cytoprotective-autophagy
#7
Jun Lin, Yiming Liu, Hao Wu, Zhihai Huang, Jingfan Ma, Chang Guo, Feng Gao, Peipei Jin, Pengfei Wei, Yunjiao Zhang, Liu Liu, Rui Zhang, Longxin Qiu, Ning Gu, Longping Wen
Transcription factor EB (TFEB) is a master regulator of autophagy and lysosomal biogenesis. Here, silver nanoparticles (Ag NPs)-induced cytoprotective autophagy required TFEB is shown. Ag NPs-induced nucleus translocation of TFEB through a well-established mechanism involving dephosphorylation of TFEB at serine-142 and serine-211 but independent of both the mTORC1 and ERK1/2 pathways. TFEB nucleus translocation precedes autophagy induced by Ag NPs and leads to enhanced expression of autophagy-essential genes...
February 19, 2018: Small
https://www.readbyqxmd.com/read/29457276/abrus-agglutinin-stimulates-bmp-2-dependent-differentiation-through-autophagic-degradation-of-%C3%AE-catenin-in-colon-cancer-stem-cells
#8
Prashanta Kumar Panda, Prajna Paramita Naik, Prakash P Praharaj, Biswa Ranjan Meher, Piyush Kumar Gupta, Rama S Verma, Tapas K Maiti, Muthu K Shanmugam, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Gautam Sethi, Rajesh Agarwal, Sujit K Bhutia
Eradicating cancer stem cells (CSCs) in colorectal cancer (CRC) through differentiation therapy is a promising approach for cancer treatment. Our retrospective tumor-specimen analysis elucidated alteration in the expression of bone morphogenetic protein 2 (BMP-2) and β-catenin during the colon cancer progression, indicating that their possible intervention through "forced differentiation" in colon cancer remission. We reveal that Abrus agglutinin (AGG) induces the colon CSCs differentiation, enhancing sensitive to the anticancer therapeutics...
February 19, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29457143/reciprocity-in-ros-and-autophagic-signaling
#9
Daric J Wible, Shawn B Bratton
Reactive oxygen species (ROS) are important signaling molecules that mediate oxidative stress and cellular damage when improperly regulated. ROS and oxidative stress can activate autophagy, which generally serves as a cytoprotective negative feedback mechanism to selectively eliminate sources of ROS, including mitochondria and peroxisomes. In this review we describe the mechanisms by which ROS directly and indirectly activate autophagy, and conversely, how selective autophagy suppresses the formation of ROS...
February 2018: Current Opinion in Toxicology
https://www.readbyqxmd.com/read/29456707/resveratrol-induces-autophagic-apoptosis-via-the-lysosomal-cathepsin-d-pathway-in-human-drug-resistant-k562-adm-leukemia-cells
#10
Zhewen Zhang, Zhuan Liu, Jing Chen, Juan Yi, Juan Cheng, Wangqing Dun, Hulai Wei
The aim of the present study was to investigate the crosstalk between resveratrol (Res)-induced autophagy and apoptosis, and the molecular pathway by which autophagy leads to apoptotic death in drug-resistant K562/ADM leukemia cells. The viability of K562/ADM cells was determined using the MTT assay. The formation of autophagic vacuoles was detected using transmission electron microscopy and monodansylcadaverine (MDC) staining. Cell apoptosis was evaluated using flow cytometry. The expression of apoptosis- or autophagy-associated proteins was measured using western blotting...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29456672/roles-of-autophagy-in-androgen-induced-benign-prostatic-hyperplasia-in-castrated-rats
#11
Rong-Fu Liu, Guo Fu, Jian Li, Yu-Feng Yang, Xue-Gang Wang, Pei-De Bai, Yue-Dong Chen
The present study investigated the role of androgen in the process of androgen-induced prostate hyperplasia in castrated rats and assessed the role of the phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/Akt/mTOR) pathway in this process. Furthermore, the extent to which autophagy may affect the level of androgen-induced benign prostatic hyperplasia was also explored. A total of 40 Sprague Dawley rats were randomly divided into four groups: Testosterone group, rapamycin group, 3-methyladenine (3-MA) group, and control group...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29456644/eudesmin-attenuates-helicobacter-pylori-induced-epithelial-autophagy-and-apoptosis-and-leads-to-eradication-of-h-pylori-infection
#12
Jai-Sing Yang, Chao-Min Wang, Chiu-Hsian Su, Han-Chen Ho, Chiung-Hung Chang, Chang-Hung Chou, Yuan-Man Hsu
Eudesmin has been proven to possess anti-inflammatory effects. In the present study, the effects of eudesmin on Helicobacter pylori (H. pylori) -mediated autophagy, apoptosis, immune response and inflammation were determined in human gastric adenocarcinoma (AGS) cells in vitro and in C57BL/6 mice in vivo . Detection of the production of interleukin (IL)-8, IL-1β and immunoglobulin M (IgM) was performed using ELISA. Identification of the activation of apoptosis-associated caspase-3, -8 and -9 proteins, Bcl-2-associated X protein (Bax) and BH3 interacting domain death agonist (Bid) protein, was determined through western blot analysis...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29456633/crosstalk-between-apoptosis-and-autophagy-in-prostate-epithelial-cells-under-androgen-deprivation
#13
Rong-Fu Liu, Jian Li, Jie Zhang, Pei-De Bai, Yu-Feng Yang, Wei Li, Zhun Wu, Jia-Xin Zheng
The present study investigated the molecular mechanism of apoptosis and autophagy in prostate epithelial cells under androgen deprivation (AD). BPH-1 cells were divided into four groups as follows: Control (Cont), AD, autophagy inhibition (AI) and AD + AI groups. Cells in the four groups were treated accordingly, and the level of apoptosis was subsequently measured via flow cytometry. The expression of the microtubule-associated proteins 1A/1B light chain 3 (LC3), caspase-3, poly (ADP-ribose) polymerase 1 (PARP-1) and Beclin-1 proteins of BPH-1 cells was detected at different time points following culture in androgen-deprived medium...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29456493/administration-of-ketamine-causes-autophagy-and-apoptosis-in-the-rat-fetal-hippocampus-and-in-pc12-cells
#14
Xinran Li, Yanan Li, Jinghua Zhao, Lina Li, Yuxin Wang, Yiming Zhang, Yue Li, Yu Chen, Wenhan Liu, Li Gao
Drug abuse during pregnancy is a serious problem. Like alcohol, anticonvulsants, sedatives, and anesthetics, such as ketamine, can pass through the placental barrier and affect the growing fetus. However, the mechanism by which ketamine causes damage to fetal rats is not well understood. Therefore, in this study, we anesthetized pregnant rats with ketamine and evaluated the Total Antioxidant Capacity (T-AOC), Reactive Oxygen Species (ROS), and Malondialdehyde (MDA). Moreover, we determined changes in the levels of Cleaved-Caspase-3 (C-Caspase-3), Beclin-1, B-cell lymphoma-2 (Bcl-2), Bcl-2 Associated X Protein (Bax), Autophagy-related gene 4 (Atg4), Atg5, p62 (SQSTM1), and marker of autophagy Light Chain 3 (LC3)...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29456132/csf-lamp2-concentrations-are-decreased-in-female-parkinson-s-disease-patients-with-lrrk2-mutations
#15
Andrea C Klaver, Mary P Coffey, Jan O Aasly, David A Loeffler
Lysosome-associated membrane glycoprotein 2 (lamp2) plays critical roles in chaperone-mediated autophagy (CMA) and macroautophagy. Its isoform lamp2a is decreased in Parkinson's disease (PD) substantia nigra. Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most known common cause of late-onset PD; although LRRK2 is thought to regulate macroautophagy, the influence of LRRK2 mutations on lamp2 concentrations in the CNS is unknown. To examine this issue we compared lamp2 levels in cerebrospinal fluid (CSF) between sporadic PD (sPD) patients (n = 31), LRRK2 PD patients (n = 20), and healthy control subjects with or without LRRK2 mutations (LRRK2 CTL = 30, CTL = 27)...
March 15, 2018: Brain Research
https://www.readbyqxmd.com/read/29455577/exploring-autophagy-with-gene-ontology
#16
Paul Denny, Marc Feuermann, David P Hill, Ruth C Lovering, Helene Plun-Favreau, Paola Roncaglia
Autophagy is a fundamental cellular process that is well conserved among eukaryotes. It is one of the strategies that cells use to catabolize substances in a controlled way. Autophagy is used for recycling cellular components, responding to cellular stresses and ridding cells of foreign material. Perturbations in autophagy have been implicated in a number of pathological conditions such as neurodegeneration, cardiac disease and cancer. The growing knowledge about autophagic mechanisms needs to be collected in a computable and shareable format to allow its use in data representation and interpretation...
February 17, 2018: Autophagy
https://www.readbyqxmd.com/read/29455545/role-of-autophagy-in-the-progress-of-coronary-total-occlusion
#17
G Demircan, O Kaplan, S B Ozdas
OBJECTIVE: In this study, we measured the level of autophagy enzyme in patients with coronary artery disease (CAD) and investigated whether the role of autophagy existed in the progress of coronary collateral and coronary total occlusion (TO). METHODS: Overall, 115 participants were included in this study. They were divided into the three groups: group 1: patients had chronic TO (n=49); group 2: patients had acute TO such as myocardial infarction (n=36); and group 3: participants were normal controls (n=30)...
2018: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/29455419/further-aspects-of-toxoplasma-gondii-elimination-in-the-presence-of-metals
#18
Laís Pessanha de Carvalho, Edésio José Tenório de Melo
Toxoplasma gondii, the etiological agent of toxoplasmosis, infects nucleated cells and then resides and multiplies within a parasitophorous vacuole. For this purpose, the parasite secretes many virulence factors for the purpose of invading and subverting the host microbicidal defenses in order to facilitate its survival in the intracellular milieu. Essential metals are structural components of proteins and enzymes or cofactors of enzymatic reactions responsible for these parasitic survival mechanisms. However, an excess of non-essential or essential metals can lead to parasite death...
February 18, 2018: Parasitology Research
https://www.readbyqxmd.com/read/29454863/potentially-functional-variants-of-atg16l2-predict-radiation-pneumonitis-and-outcomes-in-patients-with-non-small-cell-lung-cancer-after-definitive-radiotherapy
#19
Juyi Wen, Hongliang Liu, Lili Wang, Xiaomeng Wang, Ning Gu, Zhensheng Liu, Ting Xu, Daniel R Gomez, Ritsuko Komaki, Zhongxing Liao, Qingyi Wei
INTRODUCTION: Autophagy not only plays an important role in the progression of cancer but also is involved in tissue inflammatory response. However, few published studies have investigated associations between functional genetic variants of autophagy-related genes and radiation pneumonitis (RP) as well as clinical outcomes in patients with non-small cell lung cancer (NSCLC) after definitive radiotherapy. METHODS: We genotyped nine potentially functional single nucleotide polymorphisms (SNPs) in four autophagy-related genes (ATG2B, ATG10, ATG12 and ATG16L2) in 393 North American NSCLC patients treated by definitive radiotherapy and assessed their associations with RP, local recurrence-free survival (LRFS), progression-free survival (PFS) and overall survival (OS) in multivariable Cox proportional hazards regression analyses...
February 15, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29454061/activation-of-nlrx1-mediated-autophagy-accelerates-the-ototoxic-potential-of-cisplatin-in-auditory-cells
#20
Haiyan Yin, Qianqian Yang, Zhixin Cao, Hongrui Li, Zhaoyan Yu, Guodong Zhang, Gaoying Sun, Rongjun Man, Haibo Wang, Jianfeng Li
To date, the mechanism (s) underlying the cisplatin-elicited ototoxicity has not been elucidated fully. Nucleotide-binding domain and leucine-rich-repeat-containing family member ×1 (NLRX1), a cytoplasmic pattern recognition receptor, is tightly related to mitochondrial function, reactive oxygen species (ROS) production, and autophagy. In this work, autophagy alteration, NLRX1 expression, ROS generation and cell injury were investigated correspondingly by immunofluorescence staining, western-blot, TEM, flow cytometry and MTT in HEI-OC1 cells of both NLRX1 overexpression and silencing in response to cisplatin stimulus...
February 14, 2018: Toxicology and Applied Pharmacology
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