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Chuanyong Zhang, Hongbing Shen, Yunjie Lu, Ji Gao, Shaopeng Zhang, Jian Gu, Hao Lu, Yongxiang Xia, Qin Zhu, Xiaofeng Qian, Feng Zhang, Keli L Hippen, Bruce R Blazar, Ling Lu, Xuehao Wang
Thymic-derived regulatory T cell (tTreg) clinical trials show therapeutic promise in the prevention of acute graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation patients. However, strategies are needed to improve tTreg proliferative ability and survival as a means to improve tTreg therapy and reduce the requirement for producing large numbers of Treg cells for adoptive tTreg transfer. Autophagy is a self-degradative process for cytosolic components, which is involved in cells death, differentiation, lymphocyte homeostasis, and tTreg function...
February 19, 2018: Cell Death & Disease
Wenjian Xu, Xi Chen, Songcai Cai, Jin Chen, Zhen Xu, Hongpeng Jia, Jing Chen
A new strategy has been introduced to successfully fabricate the hydrophobic barriers of PADs by using organofluorine-modified superhydrophobic TiO2 NPs. Superhydrophobic TiO2-140 NPs with high-photoactivity can be converted to hydrophilicity by self-degradation of surface organic moieties under full spectrum light irradiation. Superhydrophobic TiO2-RT NPs with low-photoactivity exhibits good hydrophobic stability under light irradiation. Thus, combining these features, the PADs have been designed and constructed by photo-induced fabrication of hydrophobic barriers on the surface of the paper...
May 1, 2018: Talanta
Stephen L Wechman, Anjan K Pradhan, Rob DeSalle, Swadesh K Das, Luni Emdad, Devanand Sarkar, Paul B Fisher
Autophagy is a functionally conserved self-degradation process that facilitates the survival of eukaryotic life via the management of cellular bioenergetics and maintenance of the fidelity of genomic DNA. The first known autophagy inducer was Beclin-1. Beclin-1 is expressed in multicellular eukaryotes ranging throughout plants to animals, comprising a nonmonophyllic group, as shown in this report via aggressive BLAST searches. In humans, Beclin-1 is a haploinsuffient tumor suppressor as biallelic deletions have not been observed in patient tumors clinically...
2018: Advances in Cancer Research
Erin E Mowers, Marina N Sharifi, Kay F MacLeod
Macro-autophagy is an ancient and highly-conserved self-degradative process that plays a homeostatic role in normal cells by eliminating organelles, pathogens and protein aggregates. Autophagy, as it is routinely referred to, also allows cells to maintain metabolic sufficiency and survive under conditions of nutrient stress by recycling the by-products of autophagic degradation, such as fatty acids, amino acids and nucleotides. Tumor cells are more reliant than normal cells on autophagy for survival in part due to their rapid growth rate, altered metabolism and nutrient deprived growth environment...
January 21, 2018: FEBS Journal
ChihFeng Tien, Liangqun Huang, Susan M Watanabe, Jordan T Speidel, Carol A Carter, Chaoping Chen
HIV-1 protease autoprocessing is responsible for liberation of free mature protease (PR) from the Gag-Pol polyprotein precursor. A cell-based model system was previously developed to examine the autoprocessing mechanism of fusion precursors carrying the p6*-PR miniprecursor sandwiched between various proteins or epitopes. We here report that precursor autoprocessing is context-dependent as its activity and outcomes can be modulated by sequences upstream of p6*-PR. This was exemplified by the 26aa maltose binding protein (MBP) signal peptide (SigP) when placed at the N-terminus of a fusion precursor...
2018: PloS One
Daniel Bello-Gil, Beatriz Maestro, Jennifer Fonseca, Nina Dinjaski, M Auxiliadora Prieto, Jesús M Sanz
Polyhydroxyalkanoates (PHAs) are biodegradable polyesters that accumulate in the cytoplasm of certain bacteria. One promising biotechnological application utilizes these biopolymers as supports for protein immobilization. Here, the PHA-binding domain of the Pseudomonas putida KT2440 PhaF phasin (BioF polypeptide) was investigated as an affinity tag for the in vitro functionalization of poly-3-hydroxybutyrate (PHB) particles with recombinant proteins, namely, full-length PhaF and two fusion proteins tagged to BioF (BioF-C-LytA and BioF-β-galactosidase, containing the choline-binding module C-LytA and the β-galactosidase enzyme, respectively)...
February 15, 2018: Applied and Environmental Microbiology
Ekaterina D Sormacheva, Peter S Sherin, Yuri P Tsentalovich
Photoinduced generation of radicals in the eye lens may play an important role in the modification of proteins leading to their coloration, aggregation, and insolubilization. The radicals can be formed via the reactions of photoexcited endogenous chromophores of the human lens with lens proteins, in particular with tryptophan residues. In the present work we studied the reactions induced by UV-A (315-400nm) light between kynurenic acid (KNA), an effective photosensitizer present in the human lens, and N-acetyl-L-tryptophan (NTrpH) under aerobic and anaerobic conditions...
October 9, 2017: Free Radical Biology & Medicine
Chiara Maniaci, Scott J Hughes, Andrea Testa, Wenzhang Chen, Douglas J Lamont, Sonia Rocha, Dario R Alessi, Roberto Romeo, Alessio Ciulli
E3 ubiquitin ligases are key enzymes within the ubiquitin proteasome system which catalyze the ubiquitination of proteins, targeting them for proteasomal degradation. E3 ligases are gaining importance as targets to small molecules, both for direct inhibition and to be hijacked to induce the degradation of non-native neo-substrates using bivalent compounds known as PROTACs (for 'proteolysis-targeting chimeras'). We describe Homo-PROTACs as an approach to dimerize an E3 ligase to trigger its suicide-type chemical knockdown inside cells...
October 10, 2017: Nature Communications
Yunfeng Zhang, Hao Huang, Xinhui Yao, Guocheng Du, Jian Chen, Zhen Kang
Streptomyces griseus trypsin (SGT) possesses enzymatic properties similar to mammalian trypsins and has great potential applications in the leather processing, bioethanol, detergent and pharmaceutical industry. Here, a new strategy was reported for improving its stable, active secretory production through engineering of its propeptide and self-degradation sites. By rationally introducing hydrophobic mutations into the N-terminus of SGT Exmt (R145I), replacing the propeptide with FPVDDDDK and engineering the α-factor signal peptide, trypsin production (amidase activity) was improved to 177...
August 4, 2017: Bioresource Technology
Xiuzhi Zhang, Haiyue Zu, Dewei Zhao, Ke Yang, Simiao Tian, Xiaoming Yu, Faqiang Lu, Baoyi Liu, Xiaobing Yu, Benjie Wang, Wei Wang, Shibo Huang, Yongxuan Wang, Zihua Wang, Zhaodong Zhang
Mg-based alloys, as the potential orthopaedic implant, can self-degrade to avoid second operation for its remove, and enable to promote bone repair; however, the underlying molecular mechanisms remain unclear. In the present study, we examined the effect of Mg ions on osteogenesis, chemotaxis and anti-alkaline stress in hFOB1.19 human osteoblast cells to simulate bone-repairing effect of a biodegradable Mg-based alloy implant in vitro, and explored the regulatory role of the transient receptor potential melastatin 7 (TRPM7)/phosphoinositide 3-kinase (PI3K) signalling pathway in the process of Mg ion-induced bone repair by knockdown of TRPM7 and antagonizing PI3K activity...
November 2017: Acta Biomaterialia
Satoshi Minami, Takeshi Yamamoto, Yoshitsugu Takabatake, Atsushi Takahashi, Tomoko Namba, Jun Matsuda, Tomonori Kimura, Jun-Ya Kaimori, Isao Matsui, Takayuki Hamano, Hiroaki Takeda, Masatomo Takahashi, Yoshihiro Izumi, Takeshi Bamba, Taiji Matsusaka, Fumio Niimura, Yoshitaka Isaka
Macroautophagy/autophagy is a self-degradation process that combats starvation. Lipids are the main energy source in kidney proximal tubular cells (PTCs). During starvation, PTCs increase fatty acid (FA) uptake, form intracellular lipid droplets (LDs), and hydrolyze them for use. The involvement of autophagy in lipid metabolism in the kidney remains largely unknown. Here, we investigated the autophagy-mediated regulation of renal lipid metabolism during prolonged starvation using PTC-specific Atg5-deficient (atg5-TSKO) mice and an in vitro serum starvation model...
October 3, 2017: Autophagy
Andrea Conte, Simona Paladino, Gaia Bianco, Dominga Fasano, Raffaele Gerlini, Mara Tornincasa, Maurizio Renna, Alfredo Fusco, Donatella Tramontano, Giovanna Maria Pierantoni
High Mobility Group A1 (HMGA1) is an architectural chromatin protein whose overexpression is a feature of malignant neoplasias with a causal role in cancer initiation and progression. HMGA1 promotes tumor growth by several mechanisms, including increase of cell proliferation and survival, impairment of DNA repair and induction of chromosome instability. Autophagy is a self-degradative process that, by providing energy sources and removing damaged organelles and misfolded proteins, allows cell survival under stress conditions...
November 2017: Cell Death and Differentiation
Ying-Jie Li, Yu-He Lei, Nan Yao, Chen-Ran Wang, Nan Hu, Wen-Cai Ye, Dong-Mei Zhang, Zhe-Sheng Chen
Multidrug resistance (MDR) occurs frequently after long-term chemotherapy, resulting in refractory cancer and tumor recurrence. Therefore, combatting MDR is an important issue. Autophagy, a self-degradative system, universally arises during the treatment of sensitive and MDR cancer. Autophagy can be a double-edged sword for MDR tumors: it participates in the development of MDR and protects cancer cells from chemotherapeutics but can also kill MDR cancer cells in which apoptosis pathways are inactive. Autophagy induced by anticancer drugs could also activate apoptosis signaling pathways in MDR cells, facilitating MDR reversal...
June 24, 2017: Chinese Journal of Cancer
Abdalhaq Rami, Julia Fekadu, Oliver Rawashdeh
BACKGROUND: Autophagy is an intracellular bulk self-degrading process in which cytoplasmic contents of abnormal proteins and excess or damaged organelles are sequestered into autophagosomes, and degraded upon fusion with lysosomes. Although autophagy is generally considered to be pro-survival, it also functions in cell death processes. We recently reported on the hippocampal, higher vulnerability to cerebral ischemia in mice lacking the circadian clock protein PERIOD1 (PER1), a phenomenon we found to be linked to a PER1-dependent modulation of the expression patterns of apoptotic/autophagic markers...
2017: Current Neurovascular Research
S Salcher, M Hermann, U Kiechl-Kohlendorfer, M J Ausserlechner, P Obexer
BACKGROUND: Neuroblastoma is the most common solid tumor in childhood and develops from undifferentiated progenitor cells of the sympathetic nervous system. In neuronal tumor cells DNA-damaging chemotherapeutic agents activate the transcription factor FOXO3 which regulates the formation of reactive oxygen species (ROS) and cell death as well as a longevity program associated with therapy resistance. We demonstrated before that C10ORF10/DEPP, a transcriptional target of FOXO3, localizes to peroxisomes and mitochondria and impairs cellular ROS detoxification...
May 25, 2017: Molecular Cancer
Søs Grønbæk Mathiassen, Daniela De Zio, Francesco Cecconi
Autophagy is a self-degradation pathway, in which cytoplasmic material is sequestered in double-membrane vesicles and delivered to the lysosome for degradation. Under basal conditions, autophagy plays a homeostatic function. However, in response to various stresses, the pathway can be further induced to mediate cytoprotection. Defective autophagy has been linked to a number of human pathologies, including neoplastic transformation, even though autophagy can also sustain the growth of tumor cells in certain contexts...
2017: Frontiers in Oncology
Yuanjian Fang, Sheng Chen, Cesar Reis, Jianmin Zhang
Autophagy is an extensive self-degradation process for the disposition of cytosolic aggregated or misfolded proteins and defective organelles. Due to different cytosolic components, autophagy pathway executes the functions of pro-survival and pro-death to maintain cellular homeostasis. The pathway plays essential roles in several neurological disorders. Subarachnoid Hemorrhage (SAH) is a devastating subtype of hemorrhagic stroke with high risk of neurological deficit and high mortality. Early brain injury (EBI) plays a role in the poor clinical course and outcome after SAH...
April 6, 2017: Current Neuropharmacology
Pierre-Michaël Coly, Pierrick Gandolfo, Hélène Castel, Fabrice Morin
Autophagy is a highly conserved self-degradative process that plays a key role in diverse cellular processes such as stress response or differentiation. A growing body of work highlights the direct involvement of autophagy in cell migration and cancer metastasis. Specifically, autophagy has been shown to be involved in modulating cell adhesion dynamics as well as epithelial-to-mesenchymal transition. After providing a general overview of the mechanisms controlling autophagosome biogenesis and cell migration, we discuss how chemotactic G protein-coupled receptors, through the repression of autophagy, may orchestrate membrane trafficking and compartmentation of specific proteins at the cell front in order to support the critical steps of directional migration...
2017: Frontiers in Neuroscience
M E Papandreou, N Tavernarakis
Autophagy, from the Greek auto (self) and phagy (eating), is a self-degradative process critical for eukaryotic cell homeostasis. Its rapidly responsive, highly dynamic nature renders this process essential for adapting to and offsetting acute/harsh conditions such as starvation, organelle dysfunction, and deoxyribonucleic acid (DNA) damage. Autophagy involves an intricate network of interacting factors with multiple levels of control. Importantly, dysregulation of autophagy has been linked to numerous debilitating pathologies, including cancer and neurodegenerative conditions in humans...
2017: Methods in Enzymology
Zhong-Hao Zhang, Qiu-Yan Wu, Rui Zheng, Chen Chen, Yao Chen, Qiong Liu, Peter R Hoffmann, Jia-Zuan Ni, Guo-Li Song
Tau pathology was recently identified as a key driver of disease progression and an attractive therapeutic target in Alzheimer's disease (AD). Selenomethionine (Se-Met), a major bioactive form of selenium (Se) in organisms with significant antioxidant capacity, reduced the levels of total tau and hyperphosphorylated tau and ameliorated cognitive deficits in younger triple transgenic AD (3xTg-AD) mice. Whether Se-Met has a similar effect on tau pathology and the specific mechanism of action in older 3xTg-AD mice remains unknown...
March 1, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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