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https://www.readbyqxmd.com/read/28646096/heat-stress-causes-dysfunctional-autophagy-in-oxidative-skeletal-muscle
#1
Alexandra J Brownstein, Shanthi Ganesan, Corey M Summers, Sarah Pearce, Benjamin J Hale, Jason W Ross, Nicholas Gabler, Jacob T Seibert, Robert P Rhoads, Lance H Baumgard, Joshua T Selsby
We have previously established that 24 h of environmental hyperthermia causes oxidative stress and have implicated mitochondria as likely contributors to this process. Given this, we hypothesized that heat stress would lead to increased autophagy/mitophagy and a reduction in mitochondrial content. To address this hypothesis pigs were housed in thermoneutral (TN; 20°C) or heat stress (35°C) conditions for 1- (HS1) or 3- (HS3) days and the red and white portions of the semitendinosus collected. We did not detect differences in glycolytic muscle...
June 2017: Physiological Reports
https://www.readbyqxmd.com/read/28646090/cellular-functions-of-wasp-family-proteins-at-a-glance
#2
REVIEW
Olga Alekhina, Ezra Burstein, Daniel D Billadeau
Proteins of the Wiskott-Aldrich syndrome protein (WASP) family function as nucleation-promoting factors for the ubiquitously expressed Arp2/3 complex, which drives the generation of branched actin filaments. Arp2/3-generated actin regulates diverse cellular processes, including the formation of lamellipodia and filopodia, endocytosis and/or phagocytosis at the plasma membrane, and the generation of cargo-laden vesicles from organelles including the Golgi, endoplasmic reticulum (ER) and the endo-lysosomal network...
June 23, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28645573/evidence-that-fetal-death-is-associated-with-placental-aging
#3
Kaushik Maiti, Zakia Sultana, Robert John Aitken, Jonathan Morris, Felicity Park, Bronwyn Andrew, Simon C Riley, Roger Smith
BACKGROUND: The risk of unexplained fetal death or stillbirth increases late in pregnancy suggesting that placental aging is an etiological factor. Aging is associated with oxidative damage to DNA, RNA and lipids. We hypothesized that placentas at more than 41 completed weeks of gestation (late-term) would show changes consistent with aging that would also be present in placentas associated with stillbirths. OBJECTIVE: We sought to determine whether placentas from late-term pregnancies and unexplained stillbirth show oxidative damage and other biochemical signs of aging...
June 20, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28642840/cytolethal-distending-toxin-enhances-radiosensitivity-in-prostate-cancer-cells-by-regulating-autophagy
#4
Hwai-Jeng Lin, Hsin-Ho Liu, Chia-Der Lin, Min-Chuan Kao, Yu-An Chen, Chuan Chiang-Ni, Zhi-Pei Jiang, Mei-Zi Huang, Chun-Jung Lin, U-Ging Lo, Li-Chiung Lin, Cheng-Kuo Lai, Ho Lin, Jer-Tsong Hsieh, Cheng-Hsun Chiu, Chih-Ho Lai
Cytolethal distending toxin (CDT) produced by Campylobacter jejuni contains three subunits: CdtA, CdtB, and CdtC. Among these three toxin subunits, CdtB is the toxic moiety of CDT with DNase I activity, resulting in DNA double-strand breaks (DSB) and, consequently, cell cycle arrest at the G2/M stage and apoptosis. Radiation therapy is an effective modality for the treatment of localized prostate cancer (PCa). However, patients often develop radioresistance. Owing to its particular biochemical properties, we previously employed CdtB as a therapeutic agent for sensitizing radioresistant PCa cells to ionizing radiation (IR)...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28642707/tetrandrine-an-activator-of-autophagy-induces-autophagic-cell-death-via-pkc-%C3%AE-inhibition-and-mtor-dependent-mechanisms
#5
Vincent Kam Wai Wong, Wu Zeng, Juan Chen, Xiao Jun Yao, Elaine Lai Han Leung, Qian Qian Wang, Pauline Chiu, Ben C B Ko, Betty Yuen Kwan Law
Emerging evidence suggests the therapeutic role of autophagic modulators in cancer therapy. This study aims to identify novel traditional Chinese medicinal herbs as potential anti-tumor agents through autophagic induction, which finally lead to autophagy mediated-cell death in apoptosis-resistant cancer cells. Using bioactivity-guided purification, we identified tetrandrine (Tet) from herbal plant, Radix stephaniae tetrandrae, as an inducer of autophagy. Across a number of cancer cell lines, we found that breast cancer cells treated with tetrandrine show an increase autophagic flux and formation of autophagosomes...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28642033/atg4b-inhibitors-with-a-benzotropolone-core-structure-block-autophagy-and-augment-efficiency-of-chemotherapy-in-mice
#6
Ammar Kurdi, Matthias Cleenewerck, Christel Vangestel, Sophie Lyssens, Wim Declercq, Jean-Pierre Timmermans, Sigrid Stroobants, Koen Augustyns, Guido R Y De Meyer, Pieter Van Der Veken, Wim Martinet
Autophagy is a cell survival mechanism hijacked by advanced tumors to endure a rough microenvironment. Late autophagy inhibitors such as (hydroxy)chloroquine have been used clinically to halt tumor progression with modest success. However, given the toxic nature of these compounds and their lack of specificity, novel targets should be considered. We recently identified a benzotropolone derivative that significantly inhibited the essential autophagy protein ATG4B. Therefore, we synthesized and tested additional benzotropolone compounds to identify a promising ATG4B inhibitor that impairs autophagy both in vitro and in vivo...
June 19, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28641621/-effect-of-down-regulatory-nucleostemin-expression-on-autophagy-activities-in-p53-null-hl-60-leukemia-cells
#7
Yuan-Yu Wei, Zhao-Bo Li, Fan Zhang, Ning-Ning Wang, Shuai Liu, Bao-Hong Yue
OBJECTIVE: Based on previous microarry and bioinformatic analysis results, to investigate the effect of nucleostemin(NS) expression down-regulation on autophagy activity in p53 null HL-60 leukemia cells, so as to provide evidence for studying mechanisms of p53-independent signal pathway of NS in details. METHODS: The autophagy activity of HL-60 cells after down-regulation of NS expression was detected with acidine orange staining, Western blot and transmission electron mcrioscope technique...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28641163/6-shogaol-induces-autophagic-cell-death-then-triggered-apoptosis-in-colorectal-adenocarcinoma-ht-29-cells
#8
Ting-Yi Li, Been-Huang Chiang
6-shogaol is a phytochemical of dietary ginger, we found that 6-shogaol could induced both autophagic and apoptotic death in human colon adenocarcinoma (HT-29) cells. Results of this study showed that 6-shogal induced cell cycle arrest, autophagy, and apoptosis in HT-29 cells in a time sequence. After 6h, 6-shogal induced apparent G2/M arrest, then the HT-29 cells formed numerous autophagosomes in each phase of the cell cycle. After 18h, increases in acidic vesicles and LAMP-1 (Lysosome-associated membrane proteins 1) showed that 6-shogaol had caused autophagic cell death...
June 19, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28639909/silencing-of-nrage-induces-autophagy-via-ampk-ulk1-atg13-signaling-pathway-in-nsclc-cells
#9
Yiyang Zhou, Nan Huang, Jianchun Wu, Ni Zhen, Ning Li, Yan Li, Yong-Xin Li
NRAGE has been reported to be overexpressed in cancer cells, especially in lung cancer cells. To determine the role of NRAGE in non-small-cell lung cancer cells, we investigated the effects of NRAGE on autophagy in non-small-cell lung cancer cells. Human A549 and H1299 cells were transfected with NRAGE-specific small-interfering RNA. The Cell Counting Kit-8 and plate clone assay showed that downregulation of NRAGE could induce the proliferation in A549 and H1299 cells. In addition, our data suggested that downregulation of NRAGE enhances autophagosome formation by immunofluorescence...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28639297/autophagy-activation-not-pgc-1%C3%AE-may-mediate-exercise-induced-improvements-in-glucose-handling-during-diet-induced-obesity
#10
Megan E Rosa-Caldwell, Jacob L Brown, David E Lee, Thomas A Blackwell, Kyle W Turner, Lemuel A Brown, Richard A Perry, Wesley S Haynie, Tyrone A Washington, Nicholas P Greene
Prevalence of glucose intolerance is at alarming levels. Efforts to promote mitochondrial biogenesis through PGC-1α to mitigate glucose intolerance have been controversial. However, physical activity remains a primary means to alleviate the condition. PURPOSE: To determine combined effects of muscle-specific overexpression of PGC-1α and physical activity on glucose handling during diet-induced obesity. METHODS: Wild-type (WT, ∼20) and PGC-1α muscle transgenic (MCK-PGC-1α, ∼20) mice were given Western diet (WD) at 8 wks age and allowed to consume food ab libitum throughout the study...
June 21, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28638925/-autophagy-and-hypoxic-ischemic-brain-injuries
#11
Yong-Qiang Li, Su Fu, Lai Wang, Bin Liu, Zhen-Yu Shi, Jin-Bo Deng
Autophagy is a highly evolutionarily conserved physiological mechanism of organism, including several stages such as autophagosomes formation, the fusion of lysosomes and autophagosomes, and autophagosomes degradation. In physiological conditions, autophagy is responsible for clearing the spoiled organelles and long-lived proteins to maintain the homeostasis of cells and organism. Meanwhile, autophagy is also involved in the formation and development of diseases, but the mechanism has not been confirmed yet...
June 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28638804/pkc-%C3%AE-marcks-signaling-promotes-intracellular-survival-of-unopsonized-burkholderia-thailandensis
#12
Sofiya N Micheva-Viteva, Yulin Shou, Kumkum Ganguly, Terry H Wu, Elizabeth Hong-Geller
Pathogenic Burkholderia rely on host factors for efficient intracellular replication and are highly refractory to antibiotic treatment. To identify host genes that are required by Burkholderia spp. during infection, we performed a RNA interference (RNAi) screen of the human kinome and identified 35 host kinases that facilitated Burkholderia thailandensis intracellular survival in human monocytic THP-1 cells. We validated a selection of host kinases using imaging flow cytometry to assess efficiency of B. thailandensis survival in the host upon siRNA-mediated knockdown...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28637020/autophagy-related-genes-are-induced-by-histone-deacetylase-inhibitor-suberoylanilide-hydroxamic-acid-via-the-activation-of-cathepsin-b-in-human-breast-cancer-cells
#13
Han Han, Jing Li, Xiuyan Feng, Hui Zhou, Shanchun Guo, Weiqiang Zhou
Autophagy is involved in modulating tumor cell motility and invasion, resistance to epithelial-to-mesenchymal transition, anoikis, and escape from immune surveillance. We have previous shown that SAHA is capable to induce several apoptosis and autophagy-related gene expression in breast cancers. However, the exact mechanisms of autophagy activation in this context have not been fully identified. Our results showed that the expression and the activity of Cathepsin B (CTSB), one of the major lysosomal cysteine proteases, were significantly increased in MDA-MB- 231 and MCF-7 cells upon SAHA treatment...
June 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636643/neuromuscular-electrical-stimulation-prevents-skeletal-muscle-dysfunction-in-adjuvant-induced-arthritis-rat
#14
Koichi Himori, Daisuke Tatebayashi, Keita Kanzaki, Masanobu Wada, Håkan Westerblad, Johanna T Lanner, Takashi Yamada
Skeletal muscle weakness is a prominent feature in patients with rheumatoid arthritis (RA). In this study, we investigated whether neuromuscular electrical stimulation (NMES) training protects against skeletal muscle dysfunction in rats with adjuvant-induced arthritis (AIA). AIA was produced by intraarticular injection of complete Freund's adjuvant into the knees of Wistar rats. For NMES training, dorsiflexor muscles were stimulated via a surface electrode (0.5 ms pulse, 50 Hz, 2 s on/4 s off). NMES training was performed every other day for three weeks and consisted of three sets produced at three min intervals...
2017: PloS One
https://www.readbyqxmd.com/read/28636635/microrna-144-3p-inhibits-autophagy-activation-and-enhances-bacillus-calmette-gu%C3%A3-rin-infection-by-targeting-atg4a-in-raw264-7-macrophage-cells
#15
Le Guo, Linlin Zhou, Qian Gao, Aijun Zhang, Jun Wei, Dantong Hong, Yuankui Chu, Xiangguo Duan, Ying Zhang, Guangxian Xu
MicroRNAs (miRNAs) are small noncoding nucleotides that play major roles in the response of host immune cells. Autophagy plays a key role in activating the antimicrobial host defense against Mycobacterium tuberculosis (M. tuberculosis). Whether miRNAs specifically influence the activation of macrophage autophagy during M. tuberculosis infection is largely unknown. In the present study, we demonstrate that Mycobacterium bovis Bacillus Calmette-Guérin (BCG) infection of macrophages leads to increased expression of miR-144-3p, which targets autophagy-related gene 4a (ATG4a), to inhibit autophagy activation and antimicrobial responses to BCG...
2017: PloS One
https://www.readbyqxmd.com/read/28635671/rab33b-controls-hepatitis-b-virus-assembly-by-regulating-core-membrane-association-and-nucleocapsid-processing
#16
Christina Bartusch, Tatjana Döring, Reinhild Prange
Many viruses take advantage of cellular trafficking machineries to assemble and release new infectious particles. Using RNA interference (RNAi), we demonstrate that the Golgi/autophagosome-associated Rab33B is required for hepatitis B virus (HBV) propagation in hepatoma cell lines. While Rab33B is dispensable for the secretion of HBV subviral envelope particles, its knockdown reduced the virus yield to 20% and inhibited nucleocapsid (NC) formation and/or NC trafficking. The overexpression of a GDP-restricted Rab33B mutant phenocopied the effect of deficit Rab33B, indicating that Rab33B-specific effector proteins may be involved...
June 21, 2017: Viruses
https://www.readbyqxmd.com/read/28633005/autophagy-impairment-mediated-by-s-nitrosation-of-atg4b-leads-to-neurotoxicity-in-response-to-hyperglycemia
#17
Yazi Li, Yuying Zhang, Lei Wang, Ping Wang, Yanhong Xue, Xiaopeng Li, Xinhua Qiao, Xu Zhang, Tao Xu, Guanghui Liu, Peng Li, Chang Chen
The majority of diabetic patients develop neuropathy and there is an increasing prevalence of neurodegeneration in the central nervous system (CNS). However, the mechanism behind is poorly understood. Here we first observed that macroautophagy/autophagy was suppressed in the hippocampus of diabetic GK rats with hyperglycemia, whereas it was unchanged in ob/ob mice without hyperglycemia. Autophagy could be directly inhibited by high glucose in mouse primary hippocampal neurons. Moreover, autophagy was protective in high-glucose-induced neurotoxicity...
June 20, 2017: Autophagy
https://www.readbyqxmd.com/read/28629357/xuefuzhuyu-decoction-protected-cardiomyocytes-against-hypoxia-reoxygenation-injury-by-inhibiting-autophagy
#18
Xiaowen Shi, Haiyan Zhu, Yuanyuan Zhang, Mingmei Zhou, Danli Tang, Huamin Zhang
BACKGROUND: XuefuZhuyu decoction (XFZY) is a well-known traditional Chinese herbal medicine for the treatment of various cardiovascular diseases, such as unstable angina pectoris and myocardial ischemia-reperfusion injury. However, the mechanism by which XFZY contributes to the amelioration of cardiac injury remains unclear. METHODS: H9C2 cells were cultured under the hypoxic condition for 10 h and reoxygenated for 2 h. In the presence of various concentrations of XFZY for 12 h, the cell viability was measured by MTT assay...
June 19, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28628913/age-dependent-effects-of-alk5-inhibition-and-mechanism-of-neuroprotection-in-neonatal-hypoxic-ischemic-brain-injury
#19
Brian H Kim, Mariano Guardia Clausi, Michelle Frondelli, Israel C Nnah, Chaitali Saqcena, Radek Dobrowolski, Steven W Levison
Neonatal encephalopathy due to hypoxic-ischemic (HI) brain injury triggers a wave of neuroinflammatory events attributed to causing the progressive degeneration and functional deficits seen weeks after the initial insult. In a recent set of studies, we evaluated the therapeutic efficacy of a small molecule antagonist for ALK5 (activin-like kinase 5 ), TGF-β receptor in a rat model of moderate perinatal HI and found significant improvements in neurologic outcomes. Here, we have extended those studies to evaluate the efficacy of delayed TGF-β receptor antagonism on postnatal day (P) 6 and P9 HI rat pups with and without hypothermia...
June 20, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28628099/toxoplasma-depends-on-lysosomal-consumption-of-autophagosomes-for-persistent-infection
#20
Manlio Di Cristina, Zhicheng Dou, Matteo Lunghi, Geetha Kannan, My-Hang Huynh, Olivia L McGovern, Tracey L Schultz, Aric J Schultz, Alyssa J Miller, Beth M Hayes, Wouter van der Linden, Carla Emiliani, Matthew Bogyo, Sébastien Besteiro, Isabelle Coppens, Vern B Carruthers
Globally, nearly 2 billion people are infected with the intracellular protozoan Toxoplasma gondii(1). This persistent infection can cause severe disease in immunocompromised people and is epidemiologically linked to major mental illnesses(2) and cognitive impairment(3). There are currently no options for curing this infection. The lack of effective therapeutics is due partly to a poor understanding of the essential pathways that maintain long-term infection. Although it is known that Toxoplasma replicates slowly within intracellular cysts demarcated with a cyst wall, precisely how it sustains itself and remodels organelles in this niche is unknown...
June 19, 2017: Nature Microbiology
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