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https://www.readbyqxmd.com/read/28813698/caspase-independent-pathway-is-related-to-nilotinib-cytotoxicity-in-cultured-cardiomyocytes
#1
Qinghui Yang, Chunhui Zhang, Hong Wei, Zenghui Meng, Guangnan Li, Yuanyuan Xu, Yanjun Chen
BACKGROUND/AIMS: Cardiotoxicity is a predominant side-effect of nilotinib during chronic myeloid leukemia treatment. The underlying molecular mechanism remains unclear. The role of autophagy and mitochondrial signaling was investigated in nilotinib-treated cardiac H9C2 cells. METHODS: Cytotoxicity was assessed using Cell Death Detection kit. Immunoblot and immunofluorescence staining was performed, and cathepsin B and caspase3 activity was assessed in nilotinib-treated H9C2 cells with or without distinct pathway inhibitor or specific siRNA...
August 15, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28813167/lipophagy-maintains-energy-homeostasis-in-the-kidney-proximal-tubule-during-prolonged-starvation
#2
Satoshi Minami, Takeshi Yamamoto, Yoshitsugu Takabatake, Atsushi Takahashi, Tomoko Namba, Jun Matsuda, Tomonori Kimura, Jun-Ya Kaimori, Isao Matsui, Takayuki Hamano, Hiroaki Takeda, Masatomo Takahashi, Yoshihiro Izumi, Takeshi Bamba, Taiji Matsusaka, Fumio Niimura, Yoshitaka Isaka
Macroautophagy/autophagy is a self-degradation process that combats starvation. Lipids are the main energy source in kidney proximal tubular cells (PTCs). During starvation, PTCs increase fatty acid (FA) uptake, form intracellular lipid droplets (LDs), and hydrolyze them for use. The involvement of autophagy in lipid metabolism in the kidney remains largely unknown. Here, we investigated the autophagy-mediated regulation of renal lipid metabolism during prolonged starvation using PTC-specific Atg5-deficient (atg5-TSKO) mice and an in vitro serum starvation model...
August 16, 2017: Autophagy
https://www.readbyqxmd.com/read/28812437/autophagy-induced-kdr-vegfr-2-activation-promotes-the-formation-of-vasculogenic-mimicry-by-glioma-stem-cells
#3
Hai-Bo Wu, Shuai Yang, Hai-Yan Weng, Qian Chen, Xi-Long Zhao, Wen-Juan Fu, Qin Niu, Yi-Fang Ping, Ji Ming Wang, Xia Zhang, Xiao-Hong Yao, Xiu-Wu Bian
Antiangiogenesis with bevacizumab, an antibody against vascular endothelial growth factor (VEGF), has been used for devascularization to limit the growth of malignant glioma. However, the benefits are transient due to elusive mechanisms underlying resistance to the antiangiogenic therapy. Glioma stem cells (GSCs) are capable of forming vasculogenic mimicry (VM), an alternative microvascular circulation independent of VEGF-driven angiogenesis. Herein, we report that the formation of VM was promoted by bevacizumab-induced macroautophagy/autophagy in GSCs, which was associated with tumor resistance to antiangiogenic therapy...
August 16, 2017: Autophagy
https://www.readbyqxmd.com/read/28804541/a-potential-role-for-the-hippo-pathway-protein-yap-in-controlling-proliferation-cell-cycle-progression-and-autophagy-in-bcpap-and-ki-thyroid-papillary-carcinoma-cells
#4
Zeming Liu, Wen Zeng, Shi Wang, Xiangwang Zhao, Yawen Guo, Pan Yu, Xingjie Yin, Chunping Liu, Tao Huang
PURPOSE: The aims were two-fold: first, to examine the expression of Yes-activated protein (YAP), a key Hippo pathway regulator, in clinical thyroid papillary carcinoma samples and to correlate this with clinicopathological parameters; second, to explore the role of YAP in regulating cell growth and division in vitro. METHODS AND RESULTS: YAP expression was determined by immunohistochemistry of clinical thyroid papillary carcinoma tissue microarrays and expression was correlated with clinicopathological parameters...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28801211/parkin-clearance-of-dysfunctional-mitochondria-regulates-ros-levels-and-increases-survival-of-human-chondrocytes
#5
Mohammad Y Ansari, Nazir M Khan, Imran Ahmad, Tariq M Haqqi
OBJECTIVE: Mitochondrial dysfunction, oxidative stress and chondrocyte death are important contributors to the development and pathogenesis of osteoarthritis (OA). In this study, we determined the expression and role of Parkin in the clearance of damaged/dysfunctional mitochondria, regulation of ROS levels and chondrocyte survival under pathological conditions. METHODS: Human chondrocytes were from the unaffected area of knee OA cartilage (n=12) and were stimulated with IL-1β to mimic pathological conditions...
August 8, 2017: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/28801209/compromised-autophagy-precedes-meniscus-degeneration-and-cartilage-damage-in-mice
#6
Jeanie Kwok Meckes, Beatriz Caramés, Merissa Olmer, William B Kiosses, Shawn P Grogan, Martin K Lotz, Darryl D D'Lima
OBJECTIVE: Autophagy is a cellular homeostasis mechanism that facilitates normal cell function and survival. Objectives of this study were to determine associations between autophagic responses with meniscus injury, joint aging, and osteoarthritis (OA), and to establish the temporal relationship with structural changes in menisci and cartilage. METHODS: Constitutive activation of autophagy during aging was measured in GFP-LC3 transgenic reporter mice between 6 and 30 months...
August 8, 2017: Osteoarthritis and Cartilage
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
#7
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/28774732/downregulation-of-tigar-sensitizes-the-antitumor-effect-of-physapubenolide-through-increasing-intracellular-ros-levels-to-trigger-apoptosis-and-autophagosome-formation-in-human-breast-carcinoma-cells
#8
Ting Ma, Yi Zhang, Chao Zhang, Jian-Guang Luo, Ling-Yi Kong
Physapubenolide (PB) is a cytotoxic withanolide isolated from Physalis angulate that was used as a traditional Chinese medicine. In this study, we investigated the role of TIGAR and ROS in PB-induced apoptosis and autophagosome formation in human breast carcinoma MDA-MB-231 and MCF-7 cells. PB induced apoptosis by decreasing mitochondrial membrane potential and elevating the Bax/Bcl-2 protein expression ratio in MDA-MB-231 and MCF-7 cells. Caspase inhibitor Z-VAD-FMK treatment partly blocked PB induced cytotoxicity, suggesting that apoptosis serves as an important role in the anti-proliferative effect of PB...
July 31, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28771872/atorvastatin-ameliorates-lps-induced-inflammatory-response-by-autophagy-via-akt-mtor-signaling-pathway
#9
Fei Han, Qing-Qing Xiao, Shi Peng, Xin-Yu Che, Li-Sheng Jiang, Qin Shao, Ben He
Macrophages play crucial roles in immune response and atherosclerosis-related cardiovascular disease. Recent evidence of macrophage autophagy has demonstrated a novel pathway through which contributes to vascular inflammation. The aim of this study was to elucidate the role of autophagy in the inhibition of inflammatory response in macrophages by atorvastatin. We found that atorvastatin promoted autophagy flow determined by up-regulating the expression of autophagy-related protein microtubule-associated protein light chain (LC3B), inducing the formation of autophagosomes and down-regulating the expression of SQSTM1/P62, which is consumed during autophagy...
August 3, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28770667/autophagy-counters-lps-mediated-suppression-of-lysozyme
#10
Sudha B Singh, Henry C Lin
Impaired Paneth cell expression of antimicrobial protein (AMP) lysozyme is found in patients with Crohn's disease with the autophagy gene ATG16L1 risk allele, in mice with mutations in autophagy genes Atg16L1, Atg5 and Atg7, and in Irgm1 knockout mice. Defective autophagy is also associated with expansion of resident Gram-negative bacteria in the intestinal lumen. These findings suggest that autophagy may control extracellular resident microbes by governing expression of lysozyme. To test the hypothesis that autophagy may have a defensive role in host response to resident extracellular microbes, we investigated the relationship between gut microbes, autophagy, and lysozyme...
August 2017: Innate Immunity
https://www.readbyqxmd.com/read/28768191/intrinsic-autophagy-is-required-for-the-maintenance-of-intestinal-stem-cells-and-for-irradiation-induced-intestinal-regeneration
#11
Jumpei Asano, Taku Sato, Shizuko Ichinose, Mihoko Kajita, Nobuyuki Onai, Shigeomi Shimizu, Toshiaki Ohteki
Autophagy is a lysosomal degradation pathway with important roles in physiological homeostasis and disease. However, the role of autophagy in intestinal stem cells (ISCs) is unclear. Here, we show that intrinsic autophagy in ISCs is important for ISC homeostasis. Mice lacking autophagy protein 5 (ATG5) in intestinal epithelial cells (iECs) (Villin-Cre: Atg5(fl/fl), hereafter Atg5(ΔIEC) mice) or in all iECs except Paneth cells (Ah-Cre: Atg5(fl/fl) mice) had significantly fewer ISCs than did control mice and showed impaired ISC-dependent intestinal recovery after irradiation...
August 1, 2017: Cell Reports
https://www.readbyqxmd.com/read/28767631/neuroprotective-effects-of-c-terminal-domain-of-tetanus-toxin-on-rat-brain-against-motorneuron-damages-after-experimental-spinal-cord-injury
#12
Murat Celal Sozbilen, Murat Oztürk, Gizem Kaftan, Taner Dagci, Halit Ozyalcin, Güliz Armagan
STUDY DESIGN: Experimental animal study investigating the efficacy of C-terminal domain of tetanus toxin application as neuroprotective effects on rat brain in a model of spinal cord injury. OBJECTIVE: The aim of the present study was to investigate the possible role of C-terminal domain of tetanus toxin (Hc-TeTx) on cell death mechanisms including apoptosis and autophagy following SCI. SUMMARY OF BACKGROUND DATA: Traumatic spinal cord injury (SCI) can lead to post-traumatic inflammation, oxidative stress, motor neuron apoptosis, necrosis and autophagy of tissue...
August 1, 2017: Spine
https://www.readbyqxmd.com/read/28761177/analysis-of-autophagy-gene-polymorphisms-in-spanish-patients-with-head-and-neck-squamous-cell-carcinoma
#13
Javier Fernández-Mateos, Raquel Seijas-Tamayo, Juan Carlos Adansa Klain, Miguel Pastor Borgoñón, Elisabeth Pérez-Ruiz, Ricard Mesía, Elvira Del Barco, Carmen Salvador Coloma, Antonio Rueda Dominguez, Javier Caballero Daroqui, Encarnación Fernández Ruiz, Juan Jesús Cruz-Hernández, Rogelio González-Sarmiento
Head and neck squamous cell carcinoma (HNSCC) is the sixth cancer on incidence worldwide. Tobacco and alcohol consumption are the most classical risk factors associated with its development. Autophagy process has a dual effect both in tumourigenesis and tumour suppressing activity. To investigate the importance of this pathway in HNSCC susceptibility, a risk factor matched case-control association study was performed with four candidate polymorphisms in autophagy genes (ATG2B, ATG5, ATG10, ATG16L1). We found an association between the variant in ATG10 rs1864183 and a higher susceptibility to develop laryngeal cancer, ATG2B rs3759601 and pharyngeal cancer and ATG16L1 rs2241880 and oral carcinoma...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28760906/mechanisms-of-action-of-vitamin-d-as-supplemental-therapy-for-pneumocystis-pneumonia
#14
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/28752968/-effects-of-triptolide-on-the-autophagy-in-synovial-spleen-and-thymus-of-rats-with-adjuvant-arthritis
#15
Lei Wan, Jian Liu, Chuan-Bing Huang, Xiao-Jun Zhang, Ya-Li Wang, Ping-Heng Zhang, Yue Sun, Lei Liu
OBJECTIVE: To determine the effect of triptolide (TP) on the expression of ATG /LC3-Ⅱ Beclin1 in synovial, spleen, and thymusof rats with adjuvant arthritis (AA). METHODS: Rats were divided for four groups: normal control (NC), model control (MC), leflunomide (LEF) treatment, and triptolide (TP)treatment, with 12 rats in each group.The AA model was established through Freund's complete adjuvant (0.1 mL each) injection into the right foot plantar skin to introduce inflammation and 10 days of tail root injection of 0...
July 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28740545/e-selectin-targeted-sialic-acid-peg-dexamethasone-micelles-for-enhanced-anti-inflammatory-efficacy-for-acute-kidney-injury
#16
Jing-Bo Hu, Xu-Qi Kang, Jing Liang, Xiao-Juan Wang, Xiao-Ling Xu, Ping Yang, Xiao-Ying Ying, Sai-Ping Jiang, Yong-Zhong Du
The effective treatment for acute kidney injury (AKI) is currently limited, and care is primarily supportive. Sialic acid (SA) is main component of Sialyl Lewis(x) antigen on the mammalian cell surface, which participates in E-selectin binding. Therefore, dexamethasone(DXM)-loaded E-selectin-targeting sialic acid-polyethylene glycol-dexamethasone (SA-PEG-DXM/DXM) conjugate micelles are designed for ameliorating AKI. The conjugates are synthesized via the esterification reaction between PEG and SA or DXM, and can spontaneously form micelles in an aqueous solution with a 65...
2017: Theranostics
https://www.readbyqxmd.com/read/28738521/ginkgo-biloba-exocarp-extracts-induces-autophagy-in-lewis-lung-cancer-cells-involving-ampk-mtor-p70s6k-signaling-pathway
#17
Chenjie Cao, Dongdong Han, Ya Su, Yu Ge, Huasheng Chen, Aihua Xu
OBJECTIVES: Ginkgo biloba L. is called a living fossil plant, and could be used for the treatment of cancer thousands of years ago in China. The extracts prepared from the Ginkgo biloba exocarp (Ginkgo biloba exocarp extracts, GBEE) has a significant anti-cancer effect. Autophagy plays an important role in the occurrence and development of cancer as programmed cell death (PCD) type II. Thus it would be interesting to study the effects and mechanisms of GBEE inducing autophagy in Lewis lung cancer (LLC) cells...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28734275/low-level-of-autophagy-related-gene-10-atg10-expression-in-the-6-hydroxydopamine-rat-model-of-parkinson-s-disease
#18
Marzieh Shams Nooraei, Ali Noori-Zadeh, Shahram Darabi, Farzad Rajaei, Zohreh Golmohammadi, Hojjat Allah Abbaszadeh
Background: Autophagy is a mechanism disassembling the damaged organelles from the cell. This study attempted to examine the expression of several autophagy-related genes in Parkinson’s disease (PD) rat model. Methods: The male Wistar rats were divided into three groups as control, sham, and lesion. In the latter group, the PD rat model was induced by the injection of 6-hydroxydopamine in the striatum.The behavioral test was conducted one (baseline) and four weeks after the surgery through apomorphine hydrochloride...
July 23, 2017: Iranian Biomedical Journal
https://www.readbyqxmd.com/read/28729463/dietary-pufas-attenuate-nlrp3-inflammasome-activation-via-enhancing-macrophage-autophagy
#19
Lulu Shen, Yan Yang, Tiantong Ou, Chia-Chi C Key, Sarah H Tong, Russel C Sequeira, Jonathan M Nelson, Yan Nie, Zhan Wang, Elena Boudyguina, Swapnil V Shewale, Xuewei Zhu
Dietary PUFAs reduce atherosclerosis and macrophage inflammation, but how NLRP3 inflammasome activation and autophagy influence PUFA-mediated atheroprotection is poorly understood. We fed Ldlr-/- mice diets containing 10% (calories) palm oil (PO) and 0.2% cholesterol, supplemented with an additional 10% of calories as PO, fish oil (FO), echium oil (EO, containing 18:4 n-3), or borage oil (BO, containing 18:3 n-6). Inflammasome activation, autophagic flux, and mitochondrial function were measured in peritoneal macrophages, blood monocytes, or liver from diet-fed mice...
July 20, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28729213/physical-exercise-increases-sestrin-2-protein-levels-and-induces-autophagy-in-the-skeletal-muscle-of-old-mice
#20
Luciene Lenhare, Barbara M Crisol, Vagner R R Silva, Carlos K Katashima, André V Cordeiro, Karina D Pereira, Augusto D Luchessi, Adelino S R da Silva, Dennys E Cintra, Leandro P Moura, José R Pauli, Eduardo R Ropelle
Sestrins and autophagy deficiencies are associated with several aging-related organic dysfunctions and metabolic disorders. Here we evaluate the effects of acute exercise on Sestrin 2 (Sesn2) protein content and autophagy markers in the skeletal muscle of experimental models of aging. Twenty-four months-old C57BL/6J male mice were submitted to a single bout of swimming exercise and the gastrocnemius muscle was evaluated by Western blot. Transcriptomic and phenotypic analysis were also performed by using strains of genetically-diverse BXD mice...
July 17, 2017: Experimental Gerontology
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