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https://www.readbyqxmd.com/read/28329063/lysosomal-proteolysis-is-associated-with-exercise-induced-improvement-of-mitochondrial-quality-control-in-aged-hippocampus
#1
Li Luo, Jia-Ru Dai, Shan-Shan Guo, A-Ming Lu, Xiao-Fang Gao, Yan-Rong Gu, Xiao-Fei Zhang, Hai-Dong Xu, Yan Wang, Zhou Zhu, Lisa J Wood, Zheng-Hong Qin
Exercise improves cognitive function in older adults, but the underlying mechanism is largely unknown. Both lysosomal degradation and mitochondrial quality control decline with age. We hypothesized that exercise ameliorates age-related cognitive decline through the improvement of mitochondrial quality control in aged hippocampus, and this effect is associated with lysosomal proteolysis. Sixteen to eighteen-month old male Sprague Dawley rats underwent swim exercise training for 10 weeks. The exercise regimen prevented cognitive decline in aged rats, reduced oxidative stress, and rejuvenated mitochondria in the aged hippocampus...
January 19, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28328069/autophagy-maintains-the-integrity-of-endothelial-barrier-in-lps-induced-lung-injury
#2
Dan Zhang, Jian Zhou, Le Chi Ye, Jing Li, Zhenzhou Wu, Yuping Li, Chichi Li
Understanding the role and underlying regulation mechanism of autophagy in lipopolysaccharide-induced lung injury (LPS-LI) may provide potentially new pharmacological targets for treatment of acute lung injury. The aim of this study was to investigate the functional significance of autophagy in LPS-LI. The autophagy of human pulmonary microvascular endothelial cells (HPMVECs) and mice was inhibited before they were challenged with LPS. In vitro, permeability, vitality and the lactate dehydrogenase (LDH) release rate of the cells were detected, the zonula occluden-1 (ZO-1) expression and the stress fiber formation were determined...
March 22, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28327651/inhibition-of-cathepsin-s-confers-sensitivity-to-methyl-protodioscin-in-oral-cancer-cells-via-activation-of-p38-mapk-jnk-signaling-pathways
#3
Ming-Ju Hsieh, Chiao-Wen Lin, Mu-Kuan Chen, Su-Yu Chien, Yu-Sheng Lo, Yi-Ching Chuang, Yi-Ting Hsi, Chia-Chieh Lin, Jui-Chieh Chen, Shun-Fa Yang
Oral cancer is one of the most common cancers in the world. Approximately 90% of oral cancers are subtyped to oral squamous cell carcinoma (OSCC). Despite advances in diagnostic techniques and improvement in treatment modalities, the prognosis remains poor. Therefore, an effective chemotherapy mechanism that enhances tumor sensitivity to chemotherapeutics is urgently needed. Methyl protodioscin (MP) is a furostanol bisglycoside with a wide range of beneficial effects, including anti-inflammatory and anti-cancer properties...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28327644/a-semisynthetic-atg3-reveals-that-acetylation-promotes-atg3-membrane-binding-and-atg8-lipidation
#4
Yi-Tong Li, Cong Yi, Chen-Chen Chen, Huan Lan, Man Pan, Shao-Jin Zhang, Yi-Chao Huang, Chao-Jian Guan, Yi-Ming Li, Li Yu, Lei Liu
Acetylation of Atg3 regulates the lipidation of the protein Atg8 in autophagy. The molecular mechanism behind this important biochemical event remains to be elucidated. We describe the first semi-synthesis of homogeneous K19/K48-diacetylated Atg3 through sequential hydrazide-based native chemical ligation. In vitro reconstitution experiments with the semi-synthetic proteins confirm that Atg3 acetylation can promote the lipidation of Atg8. We find that acetylation of Atg3 enhances its binding to phosphatidylethanolamine-containing liposomes and to endoplasmic reticulum, through which it promotes the lipidation process...
March 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28327616/genetic-control-of-autophagy-underlies-pathogenesis-of-inflammatory-bowel-disease
#5
REVIEW
K G Lassen, R J Xavier
Autophagy contributes to cellular homeostasis in the face of nutrient deprivation and other cellular stresses. Cell type-specific functions for autophagy are critical in maintaining homeostasis at both the tissue level and at the whole-organism level. Recent work has highlighted the ways in which human genetic variants modulate autophagy to alter epithelial and immune responses in inflammatory bowel disease.Mucosal Immunology advance online publication 22 March 2017. doi:10.1038/mi.2017.18.
March 22, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28327409/mir-23a-5p-modulates-mycobacterial-survival-and-autophagy-during-mycobacterium-tuberculosis-infection-through-tlr2-myd88-nf-%C3%AE%C2%BAb-pathway-by-targeting-tlr2
#6
Xing Gu, Yan Gao, De-Guang Mu, En-Qing Fu
Autophagy plays a pivotal role in activating the antimicrobial host defense against Mycobacterium tuberculosis (M.tb.). The emerging roles of microRNAs (miRNAs) in regulating immune responses have attracted increasing attention in recent years. Appreciating the potential of host-directed therapies designed to control autophagy during mycobacterial infection, we focused on the influence of miR-23a-5p on the activation of macrophage autophagy during M.tb. infection in bone marrow-derived macrophages (BMDMs) and murine RAW264...
March 18, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28327001/autophagy-promotes-the-repair-of-radiation-induced-dna-damage-in-bone-marrow-hematopoietic-cells-via-enhanced-stat3-signaling
#7
Fei Xu, Xin Li, Lili Yan, Na Yuan, Yixuan Fang, Yan Cao, Li Xu, Xiaoying Zhang, Lan Xu, Chaorong Ge, Ni An, Gaoyue Jiang, Jialing Xie, Han Zhang, Jiayi Jiang, Xiaotian Li, Lei Yao, Suping Zhang, Daohong Zhou, Jianrong Wang
Autophagy protects hematopoietic cells from radiation damage in part by promoting DNA damage repair. However, the molecular mechanisms by which autophagy regulates DNA damage repair remain largely elusive. Here, we report that this radioprotective effect of autophagy depends on STAT3 signaling in murine bone marrow mononuclear cells (BM-MNCs). Specifically, we found that STAT3 activation and nuclear translocation in BM-MNCs were increased by activation of autophagy with an mTOR inhibitor and decreased by knockout of the autophagy gene Atg7...
March 2017: Radiation Research
https://www.readbyqxmd.com/read/28325912/lysosomal-activity-maintains-glycolysis-and-cyclin-e1-expression-by-mediating-ad4bp-sf-1-stability-for-proper-steroidogenic-cell-growth
#8
Jhih-Siang Syu, Takashi Baba, Jyun-Yuan Huang, Hidesato Ogawa, Chi-Han Hsieh, Jin-Xian Hu, Ting-Yu Chen, Tzu-Chien Lin, Megumi Tsuchiya, Ken-Ichirou Morohashi, Bu-Miin Huang, Fu-L Lu, Chia-Yih Wang
The development and differentiation of steroidogenic organs are controlled by Ad4BP/SF-1 (adrenal 4 binding protein/steroidogenic factor 1). Besides, lysosomal activity is required for steroidogenesis and also enables adrenocortical cell to survive during stress. However, the role of lysosomal activity on steroidogenic cell growth is as yet unknown. Here, we showed that lysosomal activity maintained Ad4BP/SF-1 protein stability for proper steroidogenic cell growth. Treatment of cells with lysosomal inhibitors reduced steroidogenic cell growth in vitro...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28325820/autophagy-and-vitamin-d
#9
Alexandra A Mushegian
Vitamin D receptor represses basal autophagy in breast tissue, which is derepressed by vitamin D, slowing cancer progression.
March 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/28325600/synthesis-and-anti-cancer-activities-of-new-sulfonamides-4-substituted-triazolyl-nucleosides
#10
Soukaina Alaoui, Maeva Dufies, Mohsine Driowya, Luc Demange, Khalid Bougrin, Guillaume Robert, Patrick Auberger, Gilles Pagès, Rachid Benhida
Nucleoside analogues are among the most known drugs commonly used in antiviral and anticancer chemotherapies. Among them, those featuring a five-membered ring nucleobase are of utmost interest such as the anti-cancer agent AICAR or the anti-viral drug ribavirin. Despite its low activity in vitro in different cell lines, AICAR is under clinical development for several pathologies, thanks to its original mode of action. Indeed, AICAR induced autophagy cell death and is able, following this mechanism, to circumvent resistance to apoptotic drugs including kinase inhibitors currently on the market...
March 9, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28325262/the-roles-of-reactive-oxygen-species-ros-and-autophagy-in-the-survival-and-death-of-leukemia-cells
#11
REVIEW
Yong-Feng Chen, Hao Liu, Xin-Jing Luo, Zhiqiang Zhao, Zhen-You Zou, Jing Li, Xiao-Jing Lin, Yong Liang
As a clonal disease of hematopoietic stem cells (HSCs), the etiology and pathogenesis of leukemia is not fully understood. Recent studies suggest that cellular homeostasis plays an essential role in maintaining the function of HSCs because dysregulation of cellular homeostasis is one of the major factors underlying the malignant transformation of HSCs. Reactive oxygen species (ROS) and autophagy, key factors regulating cellular homeostasis, are commonly observed in the human body. Autophagy can be induced by ROS through a variety of signaling pathways, and conversely inhibits ROS-induced damage to cells and tissues...
April 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28324658/mitochondrial-respiration-links-tor-complex-2-signaling-to-calcium-regulation-and-autophagy
#12
Ariadne Vlahakis, Nerea Lopez Muniozguren, Ted Powers
The Target of Rapamycin (TOR) kinase is a conserved regulator of cell growth and functions within 2 different protein complexes, TORC1 and TORC2, where TORC2 positively controls macroautophagy/autophagy during amino acid starvation. Under these conditions, TORC2 signaling inhibits the activity of the calcium-regulated phosphatase calcineurin and promotes the general amino acid control (GAAC) response and autophagy. Here we demonstrate that TORC2 regulates calcineurin by controlling the respiratory activity of mitochondria...
March 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28324492/detection-of-hypoxia-induced-and-iron-depletion-induced-mitophagy-in-mammalian-cells
#13
Shun-Ichi Yamashita, Tomotake Kanki
Mitochondrial quality and quantity are not only regulated by mitochondrial fusion and fission but also by mitochondria degradation. Mitophagy, an autophagy specific for damaged or unnecessary mitochondria, is believed to be an important pathway for mitochondrial homeostasis. To date, several stimuli are known to induce mitophagy. Some of these stimuli, however, including hypoxia, iron depletion, and nitrogen starvation, induce mild mitophagy, which is difficult to detect through decreased mitochondrial mass...
March 22, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28324487/mitophagy-in-yeast-a-screen-of-mitophagy-deficient-mutants
#14
Kentaro Furukawa, Tomotake Kanki
Mitochondrial autophagy (mitophagy) is a process that selectively degrades mitochondria via autophagy. Recent studies have shown that mitophagy plays an important role in mitochondrial homeostasis by degrading damaged or excess mitochondria. The budding yeast Saccharomyces cerevisiae is a powerful model organism that has been employed to study several biological phenomena. Recently, there has been significant progress in the understanding of mitophagy in yeast following the identification of Atg32, a mitochondrial outer membrane receptor protein for mitophagy...
March 22, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28324486/mitopho8%C3%AE-60-assay-as-a-tool-to-quantitatively-measure-mitophagy-activity
#15
Zhiyuan Yao, Xu Liu, Daniel J Klionsky
Mitophagy, a selective type of macroautophagy (hereafter referred to as autophagy), specifically mediates the vacuole/lysosome-dependent degradation of damaged or surplus mitochondria. Because this process regulates the number and quality of mitochondria, it is vital for proper cellular homeostasis. Mitophagy also plays critical roles in the clearance of paternal mitochondria in C. elegans embryos, in erythroid cell maturation, and in the prevention of neurodegenerative disease and cancer. In order to study the molecular mechanism and regulation of mitophagy, sensitive assays are necessary to quantitatively measure mitophagy activity...
March 22, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28324201/potential-roles-of-mitochondria-associated-er-membranes-mams-in-traumatic-brain-injury
#16
REVIEW
Dongdong Sun, Xin Chen, Gang Gu, Jianhao Wang, Jianning Zhang
The endoplasmic reticulum (ER) and mitochondria have both been shown to be critical in cellular homeostasis. The functions of the ER and mitochondria are independent but interrelated. These two organelles could form physical interactions, known as MAMs, to regulate physiological functions between ER and mitochondria to maintain Ca(2+), lipid, and metabolite exchange. Several proteins are located in MAMs, including RNA-dependent protein kinase (PKR)-like ER kinase, inositol 1,4,5-trisphosphate receptors, phosphofurin acidic cluster sorting protein-2 and sigma-1 receptor to ensure regulation...
March 21, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28323983/autophagic-degradation-of-collagen-1a1-by-cortisol-in-human-amnion-fibroblasts
#17
Yabing Mi, Wangsheng Wang, Chuyue Zhang, Chao Liu, Jiangwen Lu, Wenjiao Li, Rujuan Zuo, Leslie Myatt, Kang Sun
Rupture of fetal membranes can initiate parturition at both term and preterm. Collagen is the crucial factor determining the tensile strength of the membranes. Toward the end of gestation, a feed-forward regeneration of cortisol via 11β-hydroxysteroid dehydrogenase 1 exists in fetal membranes. It remains undetermined whether cortisol contributes to collagen reduction in fetal membranes. Here we have examined whether cortisol accumulation is a causative factor for collagen reduction in human amnion fibroblasts, the major source of collagens in the membranes...
January 17, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323964/dysregulated-autophagy-in-hepatocytes-promotes-bisphenol-a-bpa-induced-hepatic-lipid-accumulation-in-male-mice
#18
Shumin Yang, Ting Li, Aipin Zhang, Rufei Gao, Chuan Peng, Lulu Liu, Qingfeng Cheng, Mei Mei, Ying Song, Xiaojiao Xiang, Chaodong Wu, Xiaoqiu Xiao, Qifu Li
Context: Accumulating evidence suggests that bisphenol A (BPA) exposure is associated with nonalcoholic fatty liver disease. Disruption of autophagy causes lipid accumulation in hepatocytes. Whether and how BPA regulates autophagy remains to be explored. Objective: We investigated the effect of BPA on autophagy in hepatocytes and examined the influence of BPA-regulated autophagy on hepatic lipid accumulation. Design: Male CD1 mice were treated with BPA for eight weeks, followed by histological and biochemical evaluation of liver lipids and autophagy...
February 21, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323521/hs1bp3-provides-a-novel-mechanism-of-negative-autophagy-regulation-through-membrane-lipids
#19
Zhangyuan Yin, Daniel J Klionsky
The formation and maturation of the autophagosome, a morphological hallmark of macroautophagy/autophagy, is tightly controlled with regard to location, timing and intensity. Various proteins have been characterized to be essential in regulating autophagosome biogenesis, whereas little is known about the roles of specific lipids and their metabolizing enzymes in this process. In a recent paper, Holland et al. identified the phosphoinositide-binding protein HS1BP3 as a novel negative regulator of autophagosome formation...
March 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28323034/co-targeting-of-egfr-and-autophagy-signaling-is-an-emerging-treatment-strategy-in-metastatic-colorectal-cancer
#20
Evangelos Koustas, Michalis V Karamouzis, Chrysovalantou Mihailidou, Dimitrios Schizas, Athanasios G Papavassiliou
The epidermal growth factor receptor (EGFR) and its associated pathway is a critical key regulator of CRC development and progression. The monoclonal antibodies (MoAbs) cetuximab and panitumumab, directed against EGFR, represent a major step forward in the treatment of metastatic Colorectal cancer (mCRC), in terms of progression-free survival and overall survival in several clinical trials. However, the activity of anti-EGFR moAbs appears to be limited to a subset of patients with mCRC. Studies have highlighted that acquired-resistance to anti-EGFR MoAbs biochemically converge into Ras/Raf/Mek/Erk and PI3K/Akt/mTOR pathways...
March 18, 2017: Cancer Letters
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