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https://www.readbyqxmd.com/read/28738541/research-progress-on-osteoarthritis-treatment-mechanisms
#1
REVIEW
Yun-Yao Gu, Jian Chen, Zhu-Long Meng, Wan-Yu Ge, Yang-Yang Bian, Shao-Wen Cheng, Chen-Kun Xing, Jiang-Ling Yao, Jian Fu, Lei Peng
Osteoarthritis is a common disease and is frequently encountered in the older population; the incidence rises sharply with age. It is estimated that more than 360 million people suffer from OA. However, the pathogenesis of osteoarthritis remains unclear, and we cannot effectively prevent the progression of OA. The aim of this review was to explore the molecular markers and signaling pathways that induce chondrocyte apoptosis in OA. We searched, using the key words osteoarthritis, chondrocyte apoptosis, autophagy, endoplasmic reticulum stress, molecular targets, and biomarkers, in PubMed, Web of Science, and Google Scholar from 1994 to 2017...
July 20, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28738277/new-ruthenium-compounds-bearing-semicarbazone-2-formylopyridine-moiety-playing-with-auxiliary-ligands-for-tuning-the-mechanism-of-biological-activity
#2
Michał Łomzik, Olga Mazuryk, Dorota Rutkowska-Zbik, Grażyna Stochel, Philippe C Gros, Małgorzata Brindell
Two ruthenium(II) complexes Ru1 and Ru2 bearing as a one ligand 2,2'-bipyridine substituted by a semicarbazone 2-formylopyridine moiety (bpySC: 5-(4-{4'-methyl-[2,2'-bipyridine]-4-yl}but-1-yn-1-yl)pyridine-2-carbaldehyde semicarbazone) and as the others 2,2'-bipyridine (bpy) and 4,7-diphenyl-1,10-phenanthroline (dip), respectively, as auxiliary ligands have been prepared. Their biological activity has been studied on murine colon carcinoma (CT26) and human lung adenocarcinoma (A549) cell lines. The anti-proliferative activity was dependent on the presence of bpy or dip in the complex, with one order of magnitude higher cytotoxicity for Ru2 (dip ligands)...
July 14, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28736525/pharmaceutical-chaperones-and-proteostasis-regulators-in-the-therapy-of-lysosomal-storage-disorders-current-perspective-and-future-promises
#3
REVIEW
Fedah E Mohamed, Lihadh Al-Gazali, Fatma Al-Jasmi, Bassam R Ali
Different approaches have been utilized or proposed for the treatment of lysosomal storage disorders (LSDs) including enzyme replacement and hematopoietic stem cell transplant therapies, both aiming to compensate for the enzymatic loss of the underlying mutated lysosomal enzymes. However, these approaches have their own limitations and therefore the vast majority of LSDs are either still untreatable or their treatments are inadequate. Missense mutations affecting enzyme stability, folding and cellular trafficking are common in LSDs resulting often in low protein half-life, premature degradation, aggregation and retention of the mutant proteins in the endoplasmic reticulum...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28736290/regulated-proteolysis-as-an-element-of-er-stress-and-autophagy-implications-for-intestinal-inflammation
#4
REVIEW
Stephanie Stengel, Berith Messner, Maren Falk-Paulsen, Nina Sommer, Philip Rosenstiel
Endoplasmic reticulum (ER) stress and autophagy are tightly controlled cellular processes, which are responsible for maintaining protein homeostasis in a cell. Impairment of the interlinking pathways have been implicated in a number of human diseases, prominently in inflammatory bowel disease, where genetic variants in several independent autophagy and ER stress related loci have been associated to increased disease risk. Autophagy is a selective quality control process, which governs the integrity of the cell by removal of aged organelles and proteins via the lysosome, but recently has been shown to actively license the outcome of other signaling pathways by guiding the proteolytic removal of signaling protein complexes (adaptophagy)...
July 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28736082/differential-proteome-expression-analysis-of-androgen-dependent-and-independent-pathways-in-lncap-prostate-cancer-cells
#5
Seho Cha, Dong Hoon Shin, Jun Ryeong Seok, Jae Kyung Myung
Prostate cancer (PC) is one of the leading causes of cancer death in men. It commonly develops in older males, but the number of younger men diagnosed with the disease has increased in recent years. Hormone therapies, such as chemical and surgical methods that inhibit androgen synthesis or androgen receptor (AR) activation, have been used for advanced disease. However, castration-resistant PC (CRPC), which exhibits androgen-independent mechanisms for activating AR, develops after a few years of such treatment and no therapy is available...
July 20, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28735240/therapeutic-effects-of-l-cysteine-in-newborn-mice-subjected-to-hypoxia-ischemia-brain-injury-via-the-cbs-h2s-system-role-of-oxidative-stress-and-endoplasmic-reticulum-stress
#6
Song Liu, Danqing Xin, Lingxiao Wang, Tiantian Zhang, Xuemei Bai, Tong Li, Yunkai Xie, Hao Xue, Shishi Bo, Dexiang Liu, Zhen Wang
Neonatal hypoxic-ischemic (HI) injury is a major cause of neonatal death and neurological dysfunction. H2S has been shown to protect against hypoxia-induced injury and apoptosis of neurons. L-Cysteine is catalyzed by cystathionine-β-synthase (CBS) in the brain and sequentially produces endogenous H2S. The present study was designed to investigate whether L-Cysteine could attenuate the acute brain injury and improve neurobehavioral outcomes following HI brain injury in neonatal mice by releasing endogenous H2S...
July 14, 2017: Redox Biology
https://www.readbyqxmd.com/read/28735096/lipid-droplet-functions-beyond-energy-storage
#7
REVIEW
Michael A Welte, Alex P Gould
Lipid droplets are cytoplasmic organelles that store neutral lipids and are critically important for energy metabolism. Their function in energy storage is firmly established and increasingly well characterized. However, emerging evidence indicates that lipid droplets also play important and diverse roles in the cellular handling of lipids and proteins that may not be directly related to energy homeostasis. Lipid handling roles of droplets include the storage of hydrophobic vitamin and signaling precursors, and the management of endoplasmic reticulum and oxidative stress...
July 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28735024/n-linked-glycosylation-of-the-p24-family-protein-p24%C3%AE-5-modulates-retrograde-golgi-to-er-transport-of-k-hdel-ligands-in-arabidopsis
#8
Noelia Pastor-Cantizano, María Jesús García-Murria, Cesar Bernat-Silvestre, María Jesús Marcote, Ismael Mingarro, Fernando Aniento
The K/HDEL receptor ERD2 mediates the transport of soluble endoplasmic reticulum (ER) resident proteins containing a C-terminal K/HDEL signal from the Golgi apparatus back to the ER via COPI (COat Protein I)-coated vesicles. Sorting of ERD2 within COPI vesicles is facilitated by p24 proteins. In particular, Arabidopsis p24δ5 has been shown to interact directly with ERD2 (via its luminal GOLD -GOLgi Dynamics- domain) and with COPI proteins (via its cytoplasmic C-terminal tail) at the acidic pH of the Golgi apparatus...
July 19, 2017: Molecular Plant
https://www.readbyqxmd.com/read/28734932/a-pyridone-derivative-activates-serca2a-by-attenuating-the-inhibitory-effect-of-phospholamban
#9
Manami Kaneko, Hisato Yamamoto, Hiroki Sakai, Yusuke Kamada, Toshiki Tanaka, Shuji Fujiwara, Synsuke Yamamoto, Hiroki Takahagi, Hideyuki Igawa, Shizuo Kasai, Masakuni Noda, Makoto Inui, Tomoyuki Nishimoto
The cardiac sarco/endoplasmic reticulum Ca(2+)-dependent ATPase 2a (SERCA2a) plays a central role in Ca(2+) handling within cardiomyocytes and is negatively regulated by phospholamban (PLN), a sarcoplasmic reticulum (SR) membrane protein. The activation of SERCA2a, which has been reported to improve cardiac dysfunction in heart failure, is a potential therapeutic approach for heart failure. Therefore, we developed a novel small molecule, compound A and characterized it both in vitro and in vivo. Compound A activated the Ca(2+)-dependent ATPase activity of cardiac SR vesicles but not that of skeletal muscle SR vesicles that lack PLN...
July 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28733852/wax-crystal-sparse-leaf-4-encoding-a-%C3%AE-ketoacyl-coenzyme-a-synthase-6-is-involved-in-rice-cuticular-wax-accumulation
#10
Lu Gan, Shanshan Zhu, Zhichao Zhao, Linglong Liu, Xiaole Wang, Zhe Zhang, Xin Zhang, Jie Wang, Jiulin Wang, Xiuping Guo, Jianmin Wan
WSL4 encodes a KCS6 protein which is required for cuticular wax accumulation in rice. Very long chain fatty acids (VLCFAs) are essential precursors for cuticular wax biosynthesis. VLCFA biosynthesis occurs in the endoplasmic reticulum and requires the fatty acid elongase (FAE) complex. The β-ketoacyl-coenzyme A synthase (KCS) catalyzes the first step of FAE-mediated VLCFA elongation. Here we characterized the Wax Crystal-Sparse Leaf 4 (WSL4) gene involved in leaf cuticular wax accumulation in rice. The wsl4 mutant displayed a pleiotropic phenotype including dwarfism, less tiller numbers and reduced surface wax load...
July 21, 2017: Plant Cell Reports
https://www.readbyqxmd.com/read/28733226/allatoregulatory-like-systems-and-changes-in-cytosolic-ca-2-modulate-feeding-behaviour-in-hydra
#11
María Eugenia Alzugaray, Jorge Rafael Ronderos
Allatotropin (AT) and allatostatin-C (AST-C) are neuropeptides originally characterized by their ability to modulate the secretion of juvenile hormones in insects. Beyond the allatoregulatory function, these neuropeptides are pleiotropic acting as myoregulators not only in insects, but also in other groups of invertebrates. We have previously proposed the existence of AT and AST-C like systems in Hydra sp., a member of the phylum Cnidaria, which is a basal group of Metazoa, sharing a common ancestor with Bilateria...
July 18, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28731225/decreased-levels-of-pdi-and-p5-in-oligodendrocytes-in-alzheimer-s-disease
#12
Yasuyuki Honjo, Takashi Ayaki, Takami Tomiyama, Tomohisa Horibe, Hidefumi Ito, Hiroshi Mori, Ryosuke Takahashi, Koji Kawakami
Protein disulfide isomerase (PDI) is a chaperone protein located in the endoplasmic reticulum (ER). Nitric oxide-induced S-nitrosylation of PDI inhibits its enzymatic activity, leading to protein accumulation and activation of the unfolded protein response. Protein disulfide isomerase P5 (P5) is a member of the PDI family that mostly localizes to the ER lumen. Both S-nitrosylated PDI and S-nitrosylated P5 are found in Alzheimer's disease (AD) brain. Previously, we showed that expression of the ER stress marker, growth arrest, and DNA damage protein (GADD34) was significantly increased in neurons and oligodendrocytes in AD brain...
July 21, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/28731040/er-stress-and-the-unfolded-protein-response-in-neurodegeneration
#13
REVIEW
Claudio Hetz, Smita Saxena
The clinical manifestation of neurodegenerative diseases is initiated by the selective alteration in the functionality of distinct neuronal populations. The pathology of many neurodegenerative diseases includes accumulation of misfolded proteins in the brain. In physiological conditions, the proteostasis network maintains normal protein folding, trafficking and degradation; alterations in this network - particularly disturbances to the function of endoplasmic reticulum (ER) - are thought to contribute to abnormal protein aggregation...
July 21, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28731030/cryo-em-structure-and-biochemical-analysis-reveal-the-basis-of-the-functional-difference-between-human-pi3kc3-c1-and-c2
#14
Meisheng Ma, Jun-Jie Liu, Yan Li, Yuwei Huang, Na Ta, Yang Chen, Hua Fu, Ming-Da Ye, Yuehe Ding, Weijiao Huang, Jia Wang, Meng-Qiu Dong, Li Yu, Hong-Wei Wang
Phosphatidylinositol 3-phosphate (PI3P) plays essential roles in vesicular trafficking, organelle biogenesis and autophagy. Two class III phosphatidylinositol 3-kinase (PI3KC3) complexes have been identified in mammals, the ATG14L complex (PI3KC3-C1) and the UVRAG complex (PI3KC3-C2). PI3KC3-C1 is crucial for autophagosome biogenesis, and PI3KC3-C2 is involved in various membrane trafficking events. Here we report the cryo-EM structures of human PI3KC3-C1 and PI3KC3-C2 at sub-nanometer resolution. The two structures share a common L-shaped overall architecture with distinct features...
July 21, 2017: Cell Research
https://www.readbyqxmd.com/read/28730529/role-of-the-golgi-apparatus-in-the-blood-brain-barrier-golgi-protection-may-be-a-targeted-therapy-for-neurological-diseases
#15
REVIEW
Shuwen Deng, Hui Liu, Ke Qiu, Hong You, Qiang Lei, Wei Lu
The blood-brain barrier (BBB) protects the brain from toxic material in the blood, provides nutrients for brain tissues, and screens harmful substances from the brain. The specific brain microvascular endothelial cells (BMVECs), tight junction between endothelial cells, and astrocytes ensure proper function of the central nervous system (CNS). Pathological factors disrupt the integrity of the BBB by destroying the normal function of endothelial cells and decreasing the production of tight junction proteins or the expression of proteins specifically localized on astrocytes...
July 20, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28729917/autophagy-endoplasmic-reticulum-stress-and-the-unfolded-protein-response-in-intracerebral-hemorrhage
#16
Mingming Niu, Xiaohong Dai, Wei Zou, Xueping Yu, Wei Teng, Qiuxin Chen, Xiaowei Sun, Weiwei Yu, Huihui Ma, Peng Liu
Intracerebral hemorrhage (ICH) is a subtype of stroke that is followed by primary and secondary brain injury. As a result of the injury, cell metabolism is disrupted and a series of stress responses are activated, such as endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), leading to the re-establishment of cell homeostasis or cell death. As an important mechanism of cell homeostasis, autophagy has been widely studied, and the associations between autophagy, ER stress, and the UPR have also been demonstrated...
2017: Translational Neuroscience
https://www.readbyqxmd.com/read/28729823/administration-of-tauroursodeoxycholic-acid-attenuates-early-brain-injury-via-akt-pathway-activation
#17
Dongdong Sun, Gang Gu, Jianhao Wang, Yan Chai, Yueshan Fan, Mengchen Yang, Xin Xu, Weiwei Gao, Fei Li, Dongpei Yin, Shuai Zhou, Xin Chen, Jianning Zhang
Traumatic brain injury (TBI) is one of the leading causes of trauma-induced mortality and disability, and emerging studies have shown that endoplasmic reticulum (ER) stress plays an important role in the pathophysiology of TBI. Tauroursodeoxycholic acid (TUDCA), a hydrophilic bile acid, has been reported to act as an ER stress inhibitor and chemical chaperone and to have the potential to attenuate apoptosis and inflammation. To study the effects of TUDCA on brain injury, we subjected mice to TBI with a controlled cortical impact (CCI) device...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28729422/o-glycosylation-modulates-the-stability-of-epidermal-growth-factor-like-repeats-and-thereby-regulates-notch-trafficking
#18
Hideyuki Takeuchi, Hongjun Yu, Huilin Hao, Megumi Takeuchi, Atsuko Ito, Huilin Li, Robert S Haltiwanger
Glycosylation in the endoplasmic reticulum (ER) is closely associated with protein folding and quality control. We recently described a non-canonical ER quality control mechanism for folding of thrombospondin type 1 repeats by Protein O-fucosyltransferase 2 (POFUT2). Epidermal Growth Factor-like (EGF) repeats are also small, cysteine rich protein motifs that can be O-glycosylated by several ER-localized enzymes including Protein O-glucosyltransferase 1 (POGLUT1) and POFUT1. Both POGLUT1 and POFUT1 modify the Notch receptor on multiple EGF repeats and are essential for full Notch function...
July 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28729348/a-new-target-for-caffeine-in-the-developing-lung-endoplasmic-reticulum-stress
#19
Philipp Rath, Claudio Nardiello, Rory E Morty
The utility of caffeine to manage apnea of prematurity is widely accepted, however, much controversy surrounds the potential for caffeine to drive post-natal lung maturation in settings of arrested lung development. Many studies have reported pathways relevant to lung injury and lung development are modulated by caffeine in vitro and in vivo, leading to the application of caffeine in experimental animal models of bronchopulmonary dysplasia (BPD). These studies have generated exciting, but at times confusing data...
July 20, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28728848/endoplasmic-reticulum-stress-participates-in-the-progress-of-senescence-and-apoptosis-of-osteoarthritis-chondrocytes
#20
Yake Liu, Hai Zhu, Xin Yan, Haoye Gu, Zhifeng Gu, Fan Liu
Endoplasmic reticulum stress (ERS) has been shown to participate in many disease pathologies. Recent reports have reported that ERS exists in human osteoarthritis (OA) chondrocytes. During OA, chondrocytes exhibit increased level of some senescence marker, such as senescence-associated β-galactosidase (SA β-gal) activity. However, the persistence and accumulation of senescent cells in various tissues can also impair function and have been involved in the pathogenesis of many age-related diseases, including OA...
July 17, 2017: Biochemical and Biophysical Research Communications
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