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https://www.readbyqxmd.com/read/28810608/mechanism-of-microrna-21-regulating-il-6-inflammatory-response-and-cell-autophagy-in-intervertebral-disc-degeneration
#1
Hao Lin, Wenzhi Zhang, Tao Zhou, Wansu Li, Ziao Chen, Chaochao Ji, Chao Zhang, Fang He
This study investigated the mechanism of microRNA-21 in regulating IL-6 inflammatory response and cell autophagy in intervertebral disc degeneration. A total of 10 patients with lumbar disc herniation accompanied by nerve root pain (observation group) and 10 patients with lumbar burst fractures (control group) were selected. The nucleus pulposus tissues of the lesion were obtained during operation for cell culture. Real-time quantitative polymerase chain reaction (PCR) was used to detect the expression of microRNA-21...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28808340/kr%C3%A3-ppel-like-factor-6-is-a-transcriptional-activator-of-autophagy-in-acute-liver-injury
#2
Svenja Sydor, Paul Manka, Jan Best, Sami Jafoui, Jan-Peter Sowa, Miguel Eugenio Zoubek, Virginia Hernandez-Gea, Francisco Javier Cubero, Julia Kälsch, Diana Vetter, Maria Isabel Fiel, Yujin Hoshida, C Billie Bian, Leonard J Nelson, Han Moshage, Klaas Nico Faber, Andreas Paul, Hideo A Baba, Guido Gerken, Scott L Friedman, Ali Canbay, Lars P Bechmann
Krüppel-like factor 6 (KLF6) is a transcription factor and tumor suppressor. We previously identified KLF6 as mediator of hepatocyte glucose and lipid homeostasis. The loss or reduction of KLF6 is linked to the progression of hepatocellular carcinoma, but its contribution to liver regeneration and repair in acute liver injury are lacking so far. Here we explore the role of KLF6 in acute liver injury models in mice, and in patients with acute liver failure (ALF). KLF6 was induced in hepatocytes in ALF, and in both acetaminophen (APAP)- and carbon tetrachloride (CCl4)-treated mice...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801668/exercise-leads-to-unfavourable-cardiac-remodelling-and-enhanced-metabolic-homeostasis-in-obese-mice-with-cardiac-and-skeletal-muscle-autophagy-deficiency
#3
Zhen Yan, Ana Kronemberger, Jay Blomme, Jarrod A Call, Hannah M Caster, Renata O Pereira, Henan Zhao, Vitor U de Melo, Rhianna C Laker, Mei Zhang, Vitor A Lira
Autophagy is stimulated by exercise in several tissues; yet the role of skeletal and cardiac muscle-specific autophagy on the benefits of exercise training remains incompletely understood. Here, we determined the metabolic impact of exercise training in obese mice with cardiac and skeletal muscle disruption of the Autophagy related 7 gene (Atg7(h&mKO)). Muscle autophagy deficiency did not affect glucose clearance and exercise capacity in lean adult mice. High-fat diet in sedentary mice led to endoplasmic reticulum stress and aberrant mitochondrial protein expression in autophagy-deficient skeletal and cardiac muscles...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28796243/exogenous-h2s-facilitating-ubiquitin-aggregates-clearance-via-autophagy-attenuates-type-2-diabetes-induced-cardiomyopathy
#4
Jichao Wu, Zhiliang Tian, Yu Sun, Cuicui Lu, Ning Liu, Zhaopeng Gao, Linxue Zhang, Shiyun Dong, Fan Yang, Xin Zhong, Changqing Xu, Fanghao Lu, Weihua Zhang
Diabetic cardiomyopathy (DCM) is a serious complication of diabetes. Hydrogen sulphide (H2S), a newly found gaseous signalling molecule, has an important role in many regulatory functions. The purpose of this study is to investigate the effects of exogenous H2S on autophagy and its possible mechanism in DCM induced by type II diabetes (T2DCM). In this study, we found that sodium hydrosulphide (NaHS) attenuated the augment in left ventricular (LV) mass and increased LV volume, decreased reactive oxygen species (ROS) production and ameliorated H2S production in the hearts of db/db mice...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28789945/ambra1-is-involved-in-t-cell-receptor-mediated-metabolic-reprogramming-through-an-atg7-independent-pathway
#5
Hisako Akatsuka, Shuhei Kuga, Kaori Masuhara, Odontuya Davaadorj, Chisa Okada, Yumi Iida, Yoshinori Okada, Nahoko Fukunishi, Takahiro Suzuki, Kazuyoshi Hosomichi, Masato Ohtsuka, Masafumi Tanaka, Ituro Inoue, Minoru Kimura, Takehito Sato
Metabolic reprogramming contributes to dynamic alteration of cell functions and characteristics. In T cells, TCR-mediated signaling evokes metabolic reprogramming and autophagy. AMBRA1 is known to serve in the facilitation of autophagy and quality control of mitochondria, but the role of AMBRA1 in T cell metabolic alteration is unknown. Here, we show that AMBRA1, but not ATG7, plays a role in TCR-mediated control of glycolytic factors and mitochondrial mass, while both AMBRA1 and ATG7 are required for autolysosome formation...
August 5, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28783177/autophagy-dependent-generation-of-axin2-cancer-stem-like-cells-promotes-hepatocarcinogenesis-in-liver-cirrhosis
#6
J Li, S B Hu, L Y Wang, X Zhang, X Zhou, B Yang, J H Li, J Xiong, N Liu, Y Li, Y Z Wu, Q C Zheng
Autophagy is a pathophysiological phenomenon in liver cirrhosis that can further progress into hepatocarcinoma. Liver cancer stem cells (CSCs) are believed to initiate hepatocarcinogenesis. To investigate the precise mechanism related to the origin of CSCs in liver cirrhosis and hepatocarcinogenesis, we labeled Axin2+ hepatic cells with EGFP in Axin2Cre;Rosa26EGFP transgenic rats, and then stratified clinical and rat liver cirrhosis samples by autophagy flux. Clinical follow-up and lineage tracing in transgenic rat liver cirrhosis revealed that while Axin2/EGFP+ hepatic cells were present in normal livers and cirrhotic livers without aberrant autophagy, hepatic Axin2/EGFP+CD90+ cells were generated exclusively in cirrhotic livers with aberrant autophagy and promoted hepatocarcinogenesis...
August 7, 2017: Oncogene
https://www.readbyqxmd.com/read/28770667/autophagy-counters-lps-mediated-suppression-of-lysozyme
#7
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/28763844/-mechanism-of-action-of-yiqi-huoxue-recipe-in-regulating-autophagy-and-reversing-liver-fibrosis
#8
B Y Wang, W Zhao, X M Niu, J H Du, N Fu, S X Zhao, Y Wang, R Q Wang, Y G Zhang, Y M Nan
Objective: To investigate the role and mechanism of action of Yiqi Huoxue Recipe (YQHXR) in regulating autophagy and reversing liver fibrosis in rats with carbon tetrachloride (CCl4)-induced liver fibrosis. Methods: Healthy male Wistar rats were intraperitoneally injected with a mixture of CCl4 (30%) and olive oil (70%) twice a week for 8 weeks to establish a rat model of liver fibrosis. The rats administered normal diet were used as control group. Furthermore, YQHXR or Fuzheng Huayu Recipe (FZHYR) was intragastrically administered to the rats...
May 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28752968/-effects-of-triptolide-on-the-autophagy-in-synovial-spleen-and-thymus-of-rats-with-adjuvant-arthritis
#9
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/28747554/kaempferol-induces-hepatocellular-carcinoma-cell-death-via-endoplasmic-reticulum-stress-chop-autophagy-signaling-pathway
#10
Haiqing Guo, Wei Lin, Xiangying Zhang, Xiaohui Zhang, Zhongjie Hu, Liying Li, Zhongping Duan, Jing Zhang, Feng Ren
Kaempferol is a flavonoid compound that has gained widespread attention due to its antitumor functions. However, the underlying mechanisms are still not clear. The present study investigated the effect of kaempferol on hepatocellular carcinoma and its underlying mechanisms. Kaempferol induced autophagy in a concentration- and time-dependent manner in HepG2 or Huh7 cells, which was evidenced by the significant increase of autophagy-related genes. Inhibition of autophagy pathway, through 3-methyladenine or Atg7 siRNA, strongly diminished kaempferol-induced apoptosis...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28733114/targeting-heat-shock-factor-1-as-an-antiviral-strategy-against-dengue-virus-replication-in%C3%A2-vitro-and-in%C3%A2-vivo
#11
Tsung-Ting Tsai, Chia-Ling Chen, Cheng-Chieh Tsai, Chiou-Feng Lin
Fever onset is correlated with viremia in dengue virus (DENV) patients. Heat shock factor 1 (HSF1), a heat stress response host transcription factor, plays a crucial role in regulating multiple cellular functions, as well as the onset of infectious diseases. This study evaluated the role of HSF1 in DENV replication as a means of regulating DENV infection in vitro and in vivo. DENV infection activated HSF1 in both Ca(2+) and protein kinase A-dependent manners. Inhibiting HSF1 effectively reduced DENV replication, not only in THP-1 cells but also in primary human monocytes...
July 18, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28731223/neferine-modulates-igf-1r-nrf2-signaling-in-doxorubicin-treated-h9c2-cardiomyoblasts
#12
Lohanathan Bharathi Priya, Rathinasamy Baskaran, Chih-Yang Huang, Viswanadha Vijaya Padma
Doxorubicin (DOX) induced cardiotoxicity is a major problem during chemotherapy of cancers. DOX-mediated suppression of type 1 IGF receptor (IGF-1R) signaling leads to cardiac dysfunction. Neferine, a bisbezylisoquinoline alkaloid from the seed embryos of Nelumbo nucifera Gaertn possesses a distinct range of pharmacological properties. Herewith, the present study attempts to elucidate the protective role of neferine against DOX induced toxicity in H9c2 rat cardiomyoblast cell line model. DOX-treated H9c2 cells significantly increased mitochondrial superoxide generation, depleted cellular antioxidant status, suppressed the activation of IGF-1R signaling via PI3K/Akt/mTOR and induced autophagy by the activation of ULK1, Beclin1, Atg7 and LC3B...
July 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28729213/physical-exercise-increases-sestrin-2-protein-levels-and-induces-autophagy-in-the-skeletal-muscle-of-old-mice
#13
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
https://www.readbyqxmd.com/read/28728293/-curcumin-induces-apoptosis-and-protective-autophagy-in-human-gastric-cancer-cells-with-different-degree-of-differentiation
#14
W Li, Y Zhou, J Yang, H H Zhang, S L Zhao, T Zhang, J Huo, P Zheng
Objective: To investigate the effect of curcumin on the apoptosis and autophagy of human gastric cancer cells with different degree of differentiation. Methods: Gastric cancer cell lines BGC-823 and MKN-28 were treated with curcumin at different concentrations. The effect of curcumin on cell proliferation was measured by MTT assay. Apoptosis was assessed by flow cytometry. Autophagy status was analyzed by acridine orange staining. The expression levels of apoptotic and autophagy-related proteins were detected by Western blot...
July 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28722539/an-autophagy-driven-pathway-of-atp-secretion-supports-the-aggressive-phenotype-of-braf-v600e-inhibitor-resistant-metastatic-melanoma-cells
#15
Shaun Martin, Aleksandra M Dudek-Peric, Abhishek D Garg, Heleen Roose, Seyma Demirsoy, Sofie Van Eygen, Freya Mertens, Peter Vangheluwe, Hugo Vankelecom, Patrizia Agostinis
The ingrained capacity of melanoma cells to rapidly evolve towards an aggressive phenotype is manifested by their increased ability to develop drug-resistance, evident in the case of vemurafenib, a therapeutic-agent targeting BRAF(V600E). Previous studies indicated a tight correlation between heightened melanoma-associated macroautophagy/autophagy and acquired Vemurafenib resistance. However, how this vesicular trafficking pathway supports Vemurafenib resistance remains unclear. Here, using isogenic human and murine melanoma cell lines of Vemurafenib-resistant and patient-derived melanoma cells with primary resistance to the BRAF(V600E) inhibitor, we found that the enhanced migration and invasion of the resistant melanoma cells correlated with an enhanced autophagic capacity and autophagosome-mediated secretion of ATP...
July 19, 2017: Autophagy
https://www.readbyqxmd.com/read/28722508/atg5-and-atg7-dependent-autophagy-in-dopaminergic-neurons-regulates-cellular-and-behavioral-responses-to-morphine
#16
Ling-Yan Su, Rongcan Luo, Qianjin Liu, Jing-Ran Su, Lu-Xiu Yang, Yu-Qiang Ding, Lin Xu, Yong-Gang Yao
The molecular basis of chronic morphine exposure remains unknown. In this study, we hypothesized that macroautophagy/autophagy of dopaminergic neurons would mediate the alterations of neuronal dendritic morphology and behavioral responses induced by morphine. Chronic morphine exposure caused Atg5 (autophagy related 5)- and Atg7 (autophagy related 7)-dependent and dopaminergic neuron-specific autophagy resulting in decreased neuron dendritic spines and the onset of addictive behaviors. In cultured primary midbrain neurons, morphine treatment significantly reduced total dendritic length and complexity, and this effect could be reversed by knockdown of Atg5 or Atg7...
July 19, 2017: Autophagy
https://www.readbyqxmd.com/read/28716053/ibrutinib-a-bruton-s-tyrosine-kinase-inhibitor-exhibits-antitumoral-activity-and-induces-autophagy-in-glioblastoma
#17
Jin Wang, Xiaoyang Liu, Yongzhi Hong, Songtao Wang, Pin Chen, Aihua Gu, Xiaoyuan Guo, Peng Zhao
BACKGROUND: Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, is a novel anticancer drug used for treating several types of cancers. In this study, we aimed to determine the role of ibrutinib on GBM. METHODS: Cell proliferation was determined by using cell viability, colony formation, and 5-ethynyl-2'-deoxyuridine (EdU) assays. Cell cycle and cell apoptosis were analyzed by flow cytometry...
July 17, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28703808/rip3-attenuates-the-pancreatic-damage-induced-by-deletion-of-atg7
#18
Xiaodong Zhou, Li Xie, Leizhou Xia, Frank Bergmann, Markus W Büchler, Guido Kroemer, Thilo Hackert, Franco Fortunato
Invalidation of pancreatic autophagy entails pancreatic atrophy, endocrine and exocrine insufficiency and pancreatitis. The aim of this study was to investigate whether depletion of Rip3, which is involved in necroptotic signaling, may attenuate the pancreatic atrophy and pancreatitis resulting from autophagy inhibition. Autophagy and necroptosis signaling were evaluated in mice lacking expression of Rip3 in all organs and Atg7 in the pancreas. Acinar cell death, inflammation and fibrosis were evaluated by using of a compendium of immunofluorescence methods and immunoblots...
July 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28703806/inhibition-of-autophagy-as-a-treatment-strategy-for-p53-wild-type-acute-myeloid-leukemia
#19
Hendrik Folkerts, Susan Hilgendorf, Albertus T J Wierenga, Jennifer Jaques, André B Mulder, Paul J Coffer, Jan Jacob Schuringa, Edo Vellenga
Here we have explored whether inhibition of autophagy can be used as a treatment strategy for acute myeloid leukemia (AML). Steady-state autophagy was measured in leukemic cell lines and primary human CD34(+) AML cells with a large variability in basal autophagy between AMLs observed. The autophagy flux was higher in AMLs classified as poor risk, which are frequently associated with TP53 mutations (TP53(mut)), compared with favorable- and intermediate-risk AMLs. In addition, the higher flux was associated with a higher expression level of several autophagy genes, but was not affected by alterations in p53 expression by knocking down p53 or overexpression of wild-type p53 or p53(R273H)...
July 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28700649/autophagy-mediates-cell-cycle-response-by-regulating-nucleocytoplasmic-transport-of-pax6-in-limbal-stem-cells-under-ultraviolet-a-stress
#20
Maria Laggner, Andreas Pollreisz, Gerald Schmidinger, Ursula Schmidt-Erfurth, Ying-Ting Chen
Limbal stem cells (LSC) account for homeostasis and regeneration of corneal epithelium. Solar ultraviolet A (UVA) is the major source causing oxidative damage in the ocular surface. Autophagy, a lysosomal degradation mechanism, is essential for physiologic function and stress defense of stem cells. PAX6, a master transcription factor governing corneal homeostasis by regulating cell cycle and cell fate of LSC, responds to oxidative stress by nucleocytoplasmic shuttling. Impaired autophagy and deregulated PAX6 have been reported in oxidative stress-related ocular surface disorders...
2017: PloS One
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