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https://www.readbyqxmd.com/read/29458142/insufficient-radiofrequency-ablation-promotes-proliferation-of-residual-hepatocellular-carcinoma-via-autophagy
#1
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/29457785/tia1-variant-drives-myodegeneration-in-multisystem-proteinopathy-with-sqstm1-mutations
#2
YouJin Lee, Per Harald Jonson, Jaakko Sarparanta, Johanna Palmio, Mohona Sarkar, Anna Vihola, Anni Evilä, Tiina Suominen, Sini Penttilä, Marco Savarese, Mridul Johari, Marie-Christine Minot, David Hilton-Jones, Paul Maddison, Patrick Chinnery, Jens Reimann, Cornelia Kornblum, Torsten Kraya, Stephan Zierz, Carolyn Sue, Hans Goebel, Asim Azfer, Stuart H Ralston, Peter Hackman, Robert C Bucelli, J Paul Taylor, Conrad C Weihl, Bjarne Udd
Multisystem proteinopathy (MSP) involves disturbances of stress granule (SG) dynamics and autophagic protein degradation that underlie the pathogenesis of a spectrum of degenerative diseases that affect muscle, brain, and bone. Specifically, identical mutations in the autophagic adaptor SQSTM1 can cause varied penetrance of 4 distinct phenotypes: amyotrophic lateral sclerosis (ALS), frontotemporal dementia, Paget's disease of the bone, and distal myopathy. It has been hypothesized that clinical pleiotropy relates to additional genetic determinants, but thus far, evidence has been lacking...
February 19, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29457374/proteasomal-function-is-impaired-in-human-osteoarthritic-chondrocytes-and-this-can-contribute-to-decreased-sox9-and-aggrecan
#3
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/29457276/abrus-agglutinin-stimulates-bmp-2-dependent-differentiation-through-autophagic-degradation-of-%C3%AE-catenin-in-colon-cancer-stem-cells
#4
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
#5
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
#6
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/29455584/hepes-activates-a-mit-tfe-dependent-lysosomal-autophagic-gene-network-in-cultured-cells-a-call-for-caution
#7
Marc J Tol, Martijn J C van der Lienden, Tanit L Gabriel, Jacob J Hagen, Saskia Scheij, Tineke Veenendaal, Judith Klumperman, Wilma E Donker-Koopman, Arthur J Verhoeven, Hermen Overkleeft, Johannes M Aerts, Carmen A Argmann, Marco van Eijk
In recent years, the lysosome has emerged as a highly dynamic, transcriptionally regulated organelle that is integral to nutrient-sensing and metabolic rewiring. This is coordinated by a lysosome-to-nucleus signaling nexus in which MTORC1 controls the subcellular distribution of the microphthalmia-transcription factor E (MiT/TFE) family of "master lysosomal regulators". Yet, despite the importance of the lysosome in cellular metabolism, the impact of traditional in vitro culture media on lysosomal dynamics and/or MiT/TFE localization has not been fully appreciated...
February 17, 2018: Autophagy
https://www.readbyqxmd.com/read/29455577/exploring-autophagy-with-gene-ontology
#8
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/29455434/elucidating-post-translational-regulation-of-mouse-creb3-in-neuro2a-cells
#9
Kentaro Oh-Hashi, Ayano Soga, Yoshihisa Naruse, Kanto Takahashi, Kazutoshi Kiuchi, Yoko Hirata
CREB3 is an ER membrane-bound transcription factor; however, post-translational regulation of CREB3, including expression, processing, and activation, is not fully characterized. We therefore constructed several types of mouse CREB3 expression genes and elucidated their expression in Neuro2a cells by treatment with stimuli and co-transfection with genes associated with ER-Golgi homeostasis, such as mutant Sar1 [H79G], GRP78, and KDEL receptor 1 (KDELR1). Interestingly, treatment of Neuro2a cells expressing Flag-tagged full-length CREB3 with monensin and nigericin induced the expression of the approximately 50 kDa N-terminal fragment; however, its cleavage was not parallel to the levels of GADD153 and LC3-II...
February 17, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29454865/inhibitory-effects-of-selenium-on-cadmium-induced-cytotoxicity-in-pc12-cells-via-regulating-oxidative-stress-and-apoptosis
#10
Kaniz Fatima Binte Hossain, Md Mostafizur Rahman, Md Tajuddin Sikder, Takeshi Saito, Toshiyuki Hosokawa, Masaaki Kurasaki
Purpose of this study is to investigate mechanism/s of cyto-protection by selenium (Na2 SeO3 ; Se4+ ) against cadmium (CdCl2 ; Cd2+ )-induced cytotoxicity using PC12 cells. In addition, Se (5, 10, 20 and 40 μM) and Cd (2.5, 5 and 10 μM)-induced cytotoxicity is determined. Cytotoxicity assays and western blot analyses confirmed that Se (≥10 μM) promotes autophagic cell death via inhibition of mTOR activation and p62 accumulation due to increase of cellular oxidative stress. On the other hand, co-presence of non-toxic Se (5 μM) and toxic Cd (5 μM) showed to increase cell viability, glutathione and glutathione peroxidase 1 (GPx1) levels, and to decrease DNA fragmentation and lactate dehydrogenase (LDH) activity compared to Cd-treated (5 μM) cells alone...
February 15, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29454061/activation-of-nlrx1-mediated-autophagy-accelerates-the-ototoxic-potential-of-cisplatin-in-auditory-cells
#11
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
https://www.readbyqxmd.com/read/29453775/effect-of-pparg-on-ages-induced-akt-mtor-signaling-associated-human-chondrocytes-autophagy
#12
Zhao-Jun Wang, Hai-Bin Zhang, Cheng Chen, Hao Huang, Jian-Xia Liang
Accumulation of advanced glycation end products (AGEs) in articular cartilage is thought to represent a major risk factor for osteoarthritis development. In this study we aimed to probe the role of AGEs in human chondrocytes and to determine the impact of the peroxisome proliferator-activated receptor-γ (PPARG) on AGEs-induced cell autophagy. Cell viability was measured after human chondrocytes were treated with different concentrations of AGEs with or without the PPARG inhibitor, T0070907, or agonist, pioglitazone...
February 17, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29453568/a-method-for-in-vivo-induction-and-ultrastructural-detection-of-mitophagy-in-sertoli-cells
#13
Nabil Eid, Yuko Ito, Akio Horibe, Hitomi Hamaoka, Yoichi Kondo
An emerging body of evidences based on in vitro studies indicate that mitophagy (selective autophagic clearance of damaged mitochondria) is a prosurvival mechanism, specifically under exposure to various stressors. Sertoli cells (SCs) play essential roles in maintenance of spermatogenesis via paracrine interactions with germ cells and other somatic cells in the testis; however, studies investigating mitophagy in SCs are still very few. In this chapter, we give a brief review of mechanisms and detection methods of mitophagy in SCs based on our recent publications on animal models of ethanol toxicity and current literature...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29453315/autophagic-flux-is-regulated-by-interaction-between-the-c-terminal-domain-of-patched1-and-atg101
#14
Lucy X Chen, Cintli C Morales-Alcala, Natalia A Riobo-Del Galdo
The Hedgehog (Hh) receptor Patched1 (PTCH1) is a well-known tumor suppressor that in its active form represses Smoothened (SMO) activity, inhibits proliferation, and induces apoptosis. The cytoplasmic C-terminal domain (CTD) regulates PTCH1 turnover and nucleates a pro-apoptotic complex. In this study, it was mechanistically determined that Autophagy Related 10 (ATG101), essential for mammalian autophagy, physically interacts with the CTD of PTCH1 and connects it to the ULK complex, which stimulates the autophagy machinery in response to changes in nutrient availability...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29452162/pseudorabies-virus-induces-autophagy-to-enhance-viral-replication-in-mouse-neuro-2a-cells-in-vitro
#15
Changmeng Xu, Mi Wang, Zhongbao Song, Zhijian Wang, Qianyu Liu, Ping Jiang, Juan Bai, Yufeng Li, Xianwei Wang
Autophagy of cytoplasmic components plays an essential role in the pathogenic infection process. Furthermore, research suggests that autophagy is an extremely important component of the innate immune response. Our study aimed to reveal the effect of virus-induced autophagy on pseudorabies virus (PRV) replication. Our results confirmed that light chain 3 (LC3)-I was converted into LC3-II after PRV infection; this transition is considered an important indicator of autophagy. Transmission electron microscopy (TEM) revealed that PRV infection could notably increase the number of autophagosomes in mouse neuro-2a (N2a) cells...
February 13, 2018: Virus Research
https://www.readbyqxmd.com/read/29452090/activation-of-calcium-sensing-receptor-mediated-autophagy-in-angiotensinii-induced-cardiac-fibrosis-in-vitro
#16
Jinyu Chi, Lei Wang, Xiaohui Zhang, Yu Fu, Yue Liu, Wenjia Chen, Wenxiu Liu, Zhiyu Shi, Xinhua Yin
Cardiac fibrosis is one of the primary mechanisms of ventricular remodeling, and there is no effective method for reversal. Activation of calcium sensing receptor (CaSR) has been reported to be involved in the development of myocardial fibrosis, but the molecular mechanism for CaSR activation has not yet been clarified and needs to be further explored. Here, we found that AngII induces cardiac fibroblast proliferation and phenotypic transformation in a dose-dependent manner with increased CaSR and autophagy related protein (Beclin1, LC3B) expression...
February 13, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29451215/effect-of-moxibustion-on-mtor-mediated-autophagy-in-rotenone-induced-parkinson-s-disease-model-rats
#17
Shu-Ju Wang, Qi Wang, Jun Ma, Pei-Hao Yu, Zhong-Ming Wang, Bin Wang
Defects in autophagy-mediated clearance of α-synuclein may be one of the key factors leading to progressive loss of dopaminergic neurons in the substantia nigra. Moxibustion therapy for Parkinson's disease has been shown to have a positive effect, but the underlying mechanism remains unknown. Based on this, we explored whether moxibustion could protect dopaminergic neurons by promoting autophagy mediated by mammalian target of rapamycin (mTOR), with subsequent elimination of α-syn. A Parkinson's disease model was induced in rats by subcutaneous injection of rotenone at the back of their necks, and they received moxibustion at Zusanli (ST36), Guanyuan (CV4) and Fengfu (GV16), for 10 minutes at every point, once per day, for 14 consecutive days...
January 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29449536/impaired-autophagic-flux-is-associated-with-the-severity-of-trauma-and-the-role-of-a-2a-r-in-brain-cells-after-traumatic-brain-injury
#18
Xu-Jia Zeng, Ping Li, Ya-Lei Ning, Yan Zhao, Yan Peng, Nan Yang, Zi-Ai Zhao, Jiang-Fan Chen, Yuan-Guo Zhou
Recent studies have shown that after traumatic brain injury (TBI), the number of autophagosomes is markedly increased in brain cells surrounding the wound; however, whether autophagy is enhanced or suppressed by TBI remains controversial. In our study, we used a controlled cortical impact system to establish models of mild, moderate and severe TBI. In the mild TBI model, the levels of autophagy-related protein 6 (Beclin1) and autophagy-related protein 12 (ATG12)-autophagy-related protein 5 (ATG5) conjugates were increased, indicating the enhanced initiation of autophagy...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29446059/the-novel-involvement-of-podocyte-autophagic-activity-in-the-pathogenesis-of-lupus-nephritis
#19
Juan Jin, Meiyu Ye, Li Zhao, Wenli Zou, Wei Shen, Hongjuan Zhang, Jianguang Gong, Qiang He
BACKGROUND: Lupus nephritis (LN) is one of the most common and severe complications in Systemic lupus erythematosus patients, and the mechanism underlining the pathogenesis of LN is still unknown. Autophagy plays vital roles in maintaining cell homeostasis and is involved in the pathogenesis of many diseases. In this study, we investigated the role of autophagy in the progression of LN. METHODS: Autophagic activities in podocytes of both LN patients (Class IV and V) and mice were evaluated...
February 15, 2018: Histology and Histopathology
https://www.readbyqxmd.com/read/29446053/systems-pharmacological-analysis-of-mitochondrial-cardiotoxicity-induced-by-selected-tyrosine-kinase-inhibitors
#20
Tanaya Vaidya, Jeff Kamta, Maher Chaar, Anusha Ande, Sihem Ait-Oudhia
Tyrosine kinase inhibitors (TKIs) are targeted therapies rapidly becoming favored over conventional cytotoxic chemotherapeutics. Our study investigates two FDA approved TKIs, DASATINIB; indicated for IMATINIB-refractory chronic myeloid leukemia, and SORAFENIB; indicated for hepatocellular carcinoma and advanced renal cell carcinoma. Limited but crucial evidence suggests that these agents can have cardiotoxic side effects ranging from hypertension to heart failure. A greater understanding of the underlying mechanisms of this cardiotoxicity are needed as concerns grow and the capacity to anticipate them is lacking...
February 14, 2018: Journal of Pharmacokinetics and Pharmacodynamics
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