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https://www.readbyqxmd.com/read/29241092/trehalose-protects-against-oxidative-stress-by-regulating-the-keap1-nrf2-and-autophagy-pathways
#1
Yuhei Mizunoe, Masaki Kobayashi, Yuka Sudo, Shukoh Watanabe, Hiromine Yasukawa, Daiki Natori, Ayana Hoshino, Arisa Negishi, Naoyuki Okita, Masaaki Komatsu, Yoshikazu Higami
Dysfunction of autophagy, which regulates cellular homeostasis by degrading organelles and proteins, is associated with pathogenesis of various diseases such as cancer, neurodegeneration and metabolic disease. Trehalose, a naturally occurring nontoxic disaccharide found in plants, insects, microorganisms and invertebrates, but not in mammals, was reported to function as a mechanistic target of the rapamycin (mTOR)-independent inducer of autophagy. In addition, trehalose functions as an antioxidant though its underlying molecular mechanisms remain unclear...
September 20, 2017: Redox Biology
https://www.readbyqxmd.com/read/29241069/mir-208a-3p-aggravates-autophagy-through-the-pdcd4-atg5-pathway-in-ang-ii-induced-h9c2-cardiomyoblasts
#2
Li Wang, Nan Ye, Xiaoyu Lian, Fei Peng, Hexi Zhang, Hui Gong
Pathological cardiac hypertrophy is the main determinant of the development of heart failure, for which there is often no effective therapy. The dysregulation of autophagy is implicated in hypertrophy, but the mechanism linking these processes is unclear. In this study, we characterized the regulatory role of miR-208a-3p in autophagy in H9c2 cardiomyoblasts induced by Angiotensin II (Ang II). We found that miR-208a-3p was up-regulated in Ang II-induced H9c2 cardiomyoblasts and in starvation-induced autophagy...
December 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29240697/cymantrenyl-nucleobases-synthesis-anticancer-antitrypanosomal-and-antimicrobial-activity-studies
#3
Artur Jabłoński, Karolina Matczak, Aneta Koceva-Chyła, Kamil Durka, Dietmar Steverding, Katarzyna Jakubiec-Krześniak, Jolanta Solecka, Damian Trzybiński, Krzysztof Woźniak, Vanesa Andreu, Gracia Mendoza, Manuel Arruebo, Krzysztof Kochel, Barbara Krawczyk, Dominik Szczukocki, Konrad Kowalski
The synthesis of four cymantrene-5-fluorouracil derivatives (1-4) and two cymantrene-adenine derivatives (5 and 6) is reported. All of the compounds were characterized by spectroscopic methods and the crystal structure of two derivatives (1 and 6), together with the previously described cymantrene-adenine compound C was determined by X-ray crystallography. While the compounds 1 and 6 crystallized in the triclinic P-1 space group, compound C crystallized in the monoclinic P2₁/m space group. The newly synthesized compounds 1-6 were tested together with the two previously described cymantrene derivatives B and C for their in vitro antiproliferative activity against seven cancer cell lines (MCF-7, MCF-7/DX, MDA-MB-231, SKOV-3, A549, HepG2m and U-87-MG), five bacterial strains Staphylococcus aureus (methicillin-sensitive, methicillin-resistant and vancomycin-intermediate strains), Staphylococcus epidermidis, and Escherichia coli, including clinical isolates of S...
December 14, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29240645/resveratrol-downregulates-biomarkers-of-sepsis-via-inhibition-of-proteasome-s-proteases
#4
Neerupma Silswal, Nidhi S Reddy, Asaf A Qureshi, Nilofer Qureshi
LPS is the main agonist of Gram-negative bacteria and initiates inflammation. We recently reported that plasmas from sepsis patients revealed increased levels of following group of biomarkers; VCAM-1, ICAM1, CRP, resistin, and proteasome LMP subunits. Our objective here was to compare effects of resveratrol (shown to be a non-specific proteasome inhibitor by us) and a known LMP7 inhibitor (ONX-0914, specific inhibitor) on proteasome's activities, as well as on inflammatory markers mentioned above in human blood monocytes...
December 13, 2017: Shock
https://www.readbyqxmd.com/read/29240292/molecular-mechanism-for-the-red-blood-cell-senescence-clock
#5
REVIEW
Katherine E Badior, Joseph R Casey
Lacking protein synthesis machinery and organelles necessary for autophagy or apoptosis, aged red blood cells (RBCs) are marked by circulating auto-antibodies for macrophage-mediated clearance. The antigen recognized by these auto-antibodies is the major protein of the RBC membrane, Band 3. To ensure regulation and specificity in clearance, the molecular "clock" must mark senescent cells in a way that differentiates them from younger cells, to prevent premature clearance. Predominant models of Band 3 senescence signaling are reviewed, and merits are discussed in light of the recently published crystal structure of the Band 3 membrane domain...
December 14, 2017: IUBMB Life
https://www.readbyqxmd.com/read/29240252/ganoderma-microsporum-immunomodulatory-protein-induces-apoptosis-and-potentiates-mitomycin-c-induced-apoptosis-in-urinary-bladder-urothelial-carcinoma-cells
#6
Sheng-Yuan Huang, Chih-Cheng Chien, Ruey-Shyang Hseu, Victoria Ying Jen Huang, Shang Ying Chiang, Chi-Jung Huang, Shao-Kuan Chen, Ru-Yin Tsai, Hsi-Ting Lin, Yu-Che Cheng
Current chemotherapy and immunotherapy treatments followed by transurethral resection for urinary bladder urothelial carcinoma (UC) usually suffers from poor prognosis and high recurrence rate. Design and modification of current formulation with the novel adjuvants is needed. A recombinant protein derived from Ganoderma microsporum named as Ganoderma microsporum immunomodulatory protein (GMIP) were used to treat UC cells. We found GMIP elicits a dose-dependent and time-dependent anti-UC cell proliferation effect, with a half-maximal inhibition concentration (IC50 ) comparable to mitomycin C (MMC), a commonly used chemotherapy agent...
December 14, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29240246/hyperthermia-enhances-radiosensitivity-of-colorectal-cancer-cells-through-ros-inducing-autophagic-cell-death
#7
Ming-Chen Ba, Hui Long, Shuai Wang, Yin-Bing Wu, Bo-Huo Zhang, Zhao-Fei Yan, Fei-Hong Yu, Shu-Zhong Cui
BACKGROUND: Hyperthermia (HT) enhances the anti-cancer effects of radiotherapy (RT), but the precise biochemical mechanisms involved are unclear. This study was aim to investigate if mild HT sensitizes colorectal cancer cells to RT through reactive oxygen species (ROS)-inducing autophagic cell death in a mice model of HCT116 human colorectal cancer. METHODS: HCT116 mice model were randomly divided into five groups: mock group, hyperthermia group (HT), radiotherapy group (RT), HT + RT group, and HT + RT +N-acetyl L-cysteine (NAC) group (HT + CT + NAC)...
December 14, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29240051/influence-of-autophagy-on-the-genesis-and-development-of-atherosclerosis-and-its-risk-factors
#8
M A Sazonova, V V Sinev, V P Karagodin, A I Ryzhkova, E V Galitsyna, V A Barinova, R I Zelinyĭ, N A Nikitina, A N Orekhov
Autophagy is a highly conservative process of degeneration during which intracellular components including soluble macromolecules (e. g., nucleic acids, proteins, carbohydrates and lipids) and dysfunctional organelles (e. g., mitochondria, peroxisomes, and the endoplasmatic reticulum) are degraded by a lysosome. Autophagy serves as a dynamic system of recycling proving cells with energy and building components. Because of it in cells of an organism new proteins and membranes can form contributing to survival of the individual under starvation conditions...
2017: Angiologii︠a︡ i Sosudistai︠a︡ Khirurgii︠a︡, Angiology and Vascular Surgery
https://www.readbyqxmd.com/read/29239661/enhancement-of-the-antimycobacterial-activity-of-macrophages-by-ajoene
#9
Ji-Ae Choi, Soo-Na Cho, Yun-Ji Lim, Junghwan Lee, Dam Go, Seon-Hwa Kim, Chang-Hwa Song
Ajoene, a garlic-derived sulfur-containing compound, has broad-spectrum antimicrobial activity. To assess the potential of ajoene for treating tuberculosis (TB), we determined whether it induces the stress response of the endoplasmic reticulum (ER), which plays an important role in TB. We showed that ajoene stimulation induced the production of ER stress sensor molecules and reactive oxygen species (ROS) levels. Ajoene-induced ROS production was dependent on c-Jun N-terminal kinase (JNK) activation. Interestingly, the inhibition of JNK activity and suppression of ROS production reduced ajoene-induced CHOP production in macrophages...
January 1, 2017: Innate Immunity
https://www.readbyqxmd.com/read/29239350/suppression-of-eef-2k-mediated-autophagy-enhances-the-cytotoxicity-of-raddeanin-a-against-human-breast-cancer-cells-in-vitro
#10
Yi-di Guan, Shi-Long Jiang, Pian Yu, Mei Wen, Yi Zhang, Song-Shu Xiao, Xiao-Jun Xu, Yan Cheng
Recent evidence shows that raddeanin A (RA), an oleanane-type triterpenoid saponin extracted from Anemone raddeana Regel, exerts remarkable cytotoxicity against cancer cells in vitro and in vivo. In addition, RA has also been found to activate autophagy in human gastric cancer cells. In this study, we investigated the molecular mechanisms underlying RA-induced autophagy as well as the relationship between RA-induced autophagy and its cytotoxicity in human breast cancer cells in vitro. Treatment with RA (2-8 μmol/L) dose-dependently enhanced autophagy, as evidenced by increased LC3 levels in breast cancer cell lines T47D, MCF-7 and MDA-MB-231...
December 14, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29239314/taking-out-the-garbage-cathepsin-d-and-calcineurin-in-neurodegeneration
#11
REVIEW
Andreas Aufschnaiter, Verena Kohler, Sabrina Büttner
Cellular homeostasis requires a tightly controlled balance between protein synthesis, folding and degradation. Especially long-lived, post-mitotic cells such as neurons depend on an efficient proteostasis system to maintain cellular health over decades. Thus, a functional decline of processes contributing to protein degradation such as autophagy and general lysosomal proteolytic capacity is connected to several age-associated neurodegenerative disorders, including Parkinson's, Alzheimer's and Huntington's diseases...
November 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29238973/demethylzeylasteral-zst93-inhibits-cell-growth-and-enhances-cell-chemosensitivity-to-gemcitabine-in-human-pancreatic-cancer-cells-via-apoptotic-and-autophagic-pathways
#12
Feng Wang, Xiaodong Tian, Zhengkui Zhang, Yongsu Ma, Xuehai Xie, Jian Liang, Chunxin Yang, Yinmo Yang
The overall 5-year survival rate of patients with human pancreatic cancer remains less than 8% because of its aggressive growth, early metastasis, and resistance to conventional chemoradiotherapy. It is essential to develop innovative and effective therapeutic agents to improve its prognosis. Demethylzeylasteral (ZST93) is a novel triterpenoid monomer extracted from the xylem of Tripterygium roots. This study aimed to assess the effects of ZST93 on cell proliferation and its role in the chemosensitivity to gemcitabine in human pancreatic cancer cells...
December 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29238892/recombinant-human-erythropoietin-protects-against-hippocampal-damage-in-developing-rats-with-seizures-by-modulating-autophagy-via-the-s6-protein-in-a-time-dependent-manner
#13
Qinrui Li, Ying Han, Junbao Du, Hongfang Jin, Jing Zhang, Manman Niu, Jiong Qin
Epilepsy is among the most common neurological disorders. Recurrent seizures result in neuronal death, cognitive deficits and intellectual disabilities in children. Currently, recombinant human erythropoietin (rhEPO) is considered to play a neuroprotective role in nervous system disorders. However, the precise mechanisms through which rhEPO modulates epilepsy remain unknown. Based on results from numerous studies, we hypothesized that rhEPO protects against hippocampal damage in developing rats with seizures probably by modulating autophagy via the ribosomal protein S6 (S6) in a time-dependent manner...
December 13, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/29238517/exogenous-h2s-restores-ischemic-post-conditioning-induced-cardioprotection-through-inhibiting-endoplasmic-reticulum-stress-in-the-aged-cardiomyocytes
#14
Weiming Sun, Jinxia Yang, Yuanzhou Zhang, Yuxin Xi, Xin Wen, Di Yuan, Yuehong Wang, Can Wei, Rui Wang, Lingyun Wu, Hongzhu Li, Changqing Xu
Background: A gasotransmitter hydrogen sulfide (H2S) plays an important physiological and pathological role in cardiovascular system. Ischemic post-conditioning (PC) provides cardioprotection in the young hearts but not in the aged hearts. Exogenous H2S restores PC-induced cardioprotection by inhibition of mitochondrial permeability transition pore opening and oxidative stress and increase of autophagy in the aged hearts. However, whether H2S contributes to the recovery of PC-induced cardioprotection via down-regulation of endoplasmic reticulum stress (ERS) in the aged hearts is unclear...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/29238039/helicobacter-pylori-vaca-induces-autophagic-cell-death-in-gastric-epithelial-cells-via-the-endoplasmic-reticulum-stress-pathway
#15
Pan Zhu, Jun Xue, Zhu-Jun Zhang, Yin-Ping Jia, Ya-Nan Tong, Dan Han, Qian Li, Yang Xiang, Xu-Hu Mao, Bin Tang
The Helicobacter pylori vacuolating cytotoxin (VacA) can promote progressive vacuolation and gastric injury and may be associated with human gastric cancer. Increasing evidence indicates that autophagy is involved in the cell death induced by VacA, but the specific mechanisms need to be further elucidated. We show here that VacA could induce autophagy and increase cell death in human gastric cancer cell lines. Further investigations revealed that inhibition of autophagy could decrease the VacA-induced cell death in AGS cells...
December 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29237845/human-cytomegalovirus-replication-is-inhibited-by-the-autophagy-inducing-compounds-trehalose-and-smer28-through-distinctively-different-mechanisms
#16
Alex E Clark, Maite Sabalza, Philip L S M Gordts, Deborah H Spector
Human Cytomegalovirus (HCMV) is the top viral cause of birth defects worldwide, and current therapies have high toxicity. We previously published that the mTOR-independent autophagy-inducing disaccharide trehalose inhibits HCMV replication in multiple cell types. Here, we examine the mechanism of inhibition and introduce the autophagy inducer SMER28 as an additional inhibitor of HCMV acting through a different mechanism. We find that trehalose induces vacuolation and acidification of vacuoles, and that debris, including debris consistent in appearance with abnormal virions, is present in multivesicular bodies...
December 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29237820/vacuole-mediated-selective-regulation-of-torc1-sch9-signaling-following-oxidative-stress
#17
Eigo Takeda, Natsuko Jin, Eisuke Itakura, Shintaro Kira, Yoshiaki Kamada, Lois S Weisman, Takeshi Noda, Akira Matsuura
Target of rapamycin complex 1 (TORC1) is a central cellular signaling coordinator that allows eukaryotic cells to adapt to the environment. In the budding yeast, Saccharomyces cerevisiae, TORC1 senses nitrogen and various stressors, and modulates proteosynthesis, nitrogen uptake and metabolism, stress responses, and autophagy. There is some indication that TORC1 may regulate these downstream pathways individually. However, the potential mechanisms for such differential regulation are unknown. Here we show that the serine/threonine protein kinase Sch9 branch of TORC1 signaling depends specifically on the integrity of the vacuolar membrane, and this dependency originates in changes in Sch9 localization reflected by phosphatidylinositol 3,5-bisphosphate...
December 13, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29237720/beyond-self-eating-the-control-of-nonautophagic-functions-and-signaling-pathways-by-autophagy-related-proteins
#18
REVIEW
Ken Cadwell, Jayanta Debnath
The identification of conserved autophagy-related proteins (ATGs) that mediate bulk degradation of cytosolic material laid the foundation for breakthroughs linking autophagy to a litany of physiological processes and disease conditions. Recent discoveries are revealing that these same ATGs orchestrate processes that are related to, and yet clearly distinct from, classic autophagy. Autophagy-related functions include secretion, trafficking of phagocytosed material, replication and egress of viral particles, and regulation of inflammatory and immune signaling cascades...
December 13, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29237558/atg7-activates-an-autophagy-essential-ubiquitin-like-protein-atg8-through-multi-step-recognition
#19
Masaya Yamaguchi, Kenji Satoo, Hironori Suzuki, Yuko Fujioka, Yoshinori Ohsumi, Fuyuhiko Inagaki, Nobuo N Noda
Atg8 is a unique ubiquitin-like protein that is covalently conjugated with a phosphatidylethanolamine through reactions similar to ubiquitination and plays essential roles in autophagy. Atg7 is the E1 enzyme for Atg8, and it activates the C-terminal Gly116 of Atg8 using ATP. Here, we report the crystal structure of Atg8 bound to the C-terminal domain of Atg7 in an unprecedented mode. Atg8 neither contacts with the central β-sheet nor binds to the catalytic site of Atg7, both of which were observed in previously reported Atg7-Atg8 structures...
December 10, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29237347/pregnancy-history-influences-the-level-of-autophagy-in-peripheral-blood-mononuclear-cells-from-pregnant-women
#20
Aswathi Jayaram, Tomi Kanninen, Giovanni Sisti, Steven R Inglis, Nurah Morgan, Steven S Witkin
OBJECTIVE: Maternal immune responses are altered during pregnancy and differ between nulliparous and multiparous women. The influence of a prior gestation on autophagy in peripheral blood mononuclear cells (PBMCs) from pregnant women has not been determined and is the subject of this investigation. METHODS: Peripheral blood mononuclear cells were isolated from 212 pregnant women and immediately lysed in the presence of protease inhibitors, and the extent of autophagy was determined by quantitation of the concentration of p62 (sequestosome-1) in the lysates by enzyme-linked immunosorbent assay (ELISA)...
January 1, 2017: Reproductive Sciences
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