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https://www.readbyqxmd.com/read/29774506/therapeutic-potential-of-mesenchymal-stem-cell-derived-exosomes-in-the-treatment-of-eye-diseases
#1
C Randall Harrell, Bojana Simovic Markovic, Crissy Fellabaum, Aleksandar Arsenijevic, Valentin Djonov, Nebojsa Arsenijevic, Vladislav Volarevic
Mesenchymal stem cells (MSCs) were, due to their immunomodulatory and pro-angiogenic characteristics, extensively explored as new therapeutic agents in cell-based therapy of uveitis, glaucoma, retinal and ocular surface diseases.Since it was recently revealed that exosomes play an important role in biological functions of MSCs, herewith we summarized current knowledge about the morphology, structure, phenotype and functional characteristics of MSC-derived exosomes emphasizing their therapeutic potential in the treatment of eye diseases...
May 18, 2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29760280/mono-ubiquitination-of-cancer-stem-cell-marker-cd133-at-lysine-848-regulates-its-secretion-and-promotes-cell-migration
#2
Fan Yang, Yang Xing, Yinan Li, Xiaoning Chen, Zhilong Ai, Yuanyan Wei, Jianhai Jiang
CD133, a widely known marker for cancer stem cells, has recently been found in extracellular vesicles. However, the mechanisms underlying CD133 translocation to the extracellular space remain largely unknown. Here, we report that CD133 is mono-ubiquitinated. Ubiquitination occurs primarily on complex glycosylated CD133. Lysine 848 residue at the intracellular carboxyl terminal is one of the sites for CD133 ubiquitination. K848R mutation does not affect CD133 degradation by the lysosomal pathway, but significantly reduces CD133 secretion...
May 14, 2018: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29750193/mammalian-eak-7-activates-alternative-mtor-signaling-to-regulate-cell-proliferation-and-migration
#3
Joe Truong Nguyen, Connor Ray, Alexandra Lucienne Fox, Daniela Baccelli Mendonça, Jin Koo Kim, Paul H Krebsbach
Nematode EAK-7 (enhancer-of- akt -1-7) regulates dauer formation and controls life span; however, the function of the human ortholog mammalian EAK-7 (mEAK-7) is unknown. We report that mEAK-7 activates an alternative mechanistic/mammalian target of rapamycin (mTOR) signaling pathway in human cells, in which mEAK-7 interacts with mTOR at the lysosome to facilitate S6K2 activation and 4E-BP1 repression. Despite interacting with mTOR and mammalian lethal with SEC13 protein 8 (mLST8), mEAK-7 does not interact with other mTOR complex 1 (mTORC1) or mTOR complex 2 (mTORC2) components; however, it is essential for mTOR signaling at the lysosome...
May 2018: Science Advances
https://www.readbyqxmd.com/read/29750121/-in-vivo-confocal-microscopic-observations-of-vortex-keratopathy-in-patients-with-amiodarone-induced-keratopathy-and-fabry-disease
#4
Yasuhito Ikegawa, Atsushi Shiraishi, Yasuhito Hayashi, Akiyoshi Ogimoto, Yuichi Ohashi
Purpose: To compare the morphology of two types of vortex keratopathy: amiodarone-induced keratopathy and the Fabry disease-associated keratopathy. Patients and Methods: Eight patients who were receiving oral amiodarone therapy and 3 patients with Fabry disease, a mother and her 2 daughters, were examined by slit-lamp biomicroscopy and in vivo confocal microscopy (IVCM) regularly. Results: Amiodarone-induced keratopathy developed in 7 of the 8 patients, and it was detected as early as 7 days by IVCM and 14 days by slit-lamp biomicroscopy...
2018: Journal of Ophthalmology
https://www.readbyqxmd.com/read/29749495/lin28a-inhibits-lysosome%C3%A2-associated-membrane-glycoprotein-1-protein-expression-in-embryonic-stem-and-bladder-cancer-cells
#5
Peng Pan, Ting Chen, Yanmin Zhang, Zhengyu Qi, Jie Qin, Guanghui Cui, Xin Guo
Tumor cells and embryonic stem cells (ESCs) have similar transcription mechanisms. LIN28A is an important factor in tumor cells and ESCs, it is an inhibitor of intracellular endoplasmic reticulum (ER)‑related protein translation in ESCs. The present study aimed to examine the effects of LIN28A on an ER‑related protein, lysosome‑associated membrane glycoprotein 1 (LAMP1), in human bladder cancer cells and mouse (m)ESCs, using reverse transcription‑quantitative polymerase chain reaction and western blotting to detect the expression of LAMP1 mRNA and protein, respectively, following LIN28A knockdown...
May 3, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29749374/microrna-125b-reverses-oxaliplatin-resistance-in-hepatocellular-carcinoma-by-negatively-regulating-eva1a-mediated-autophagy
#6
Wei-Wei Ren, Dan-Dan Li, Xiao-Long Li, Ya-Ping He, Le-Hang Guo, Lin-Na Liu, Hui-Xiong Xu, Li-Ping Sun, Xiao-Ping Zhang
EVA1A (also known as transmembrane protein 166) is a transmembrane protein involved in the regulation of autophagy that acts as an adaptor protein to recruit or bind proteins in the lysosome or endoplasmic reticulum. In the present study, we identified EVA1A as a target of microRNA-125b (miR-125b), a member of a highly conserved family of miRNAs that has been proposed as a biomarker for hepatocellular carcinoma (HCC). Analysis of oxaliplatin-sensitive and oxaliplatin-resistant HCC cell lines showed that miR-125b is downregulated in resistant cells and its overexpression in sensitive cells decreased resistance to oxaliplatin by inhibiting cell proliferation, migration and epithelial-mesenchymal transition (EMT)...
May 10, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29707067/pegylated-tio-2-nanoparticles-mediated-inhibition-of-cell-migration-via-integrin-beta-1
#7
Qingqing Sun, Koki Kanehira, Akiyoshi Taniguchi
Nanoparticles (NPs) elicit various physiological responses in cellular environment, and the effect of NPs on cell migration is of high interest. In this work, the effects of NPs on cell migration and their possible mechanisms were studied. Here, we showed that after exposure to pegylated titanium dioxide nanoparticles (TiO2 -PEG NPs, where PEG stands for the polyethylene glycol), NCI-H292 cells exhibited slower migration than control cells. Furthermore, larger NPs inhibited cell migration much stronger than smaller NPs...
2018: Science and Technology of Advanced Materials
https://www.readbyqxmd.com/read/29693408/calpains-diverse-functions-but-enigmatic
#8
REVIEW
Masoumeh Hosseini, Hossein Najmabadi, Kimia Kahrizi
Calpains are a group of non-lysosomal Ca2+ -dependent cysteine proteases with numerous substrates. Calpains have been identified in almost all eukaryotes and bacteria but not in archaebacteria. In the human genome, this group of enzymes has 15 isoforms and is present ubiquitously and demonstrates tissue-specific patterns of expression. Calpains are involved in different physiological and pathological processes such as cell proliferation, migration, invasion, apoptosis and signal transduction and their roles in various disorders have been reported...
April 1, 2018: Archives of Iranian Medicine
https://www.readbyqxmd.com/read/29668344/phenotypic-plasticity-of-mesenchymal-stem-cells-is-crucial-for-mesangial-repair-in-a-model-of-immunoglobulin-light-chain-associated-mesangial-damage
#9
Guillermo A Herrera, Jiamin Teng, Chun Zeng, Hongzhi Xu, Man Liang, J Steven Alexander, Bing Liu, Chris Boyer, Elba A Turbat-Herrera
Mesangiopathies produced by glomerulopathic monoclonal immunoglobulin light chains (GLCs) acting on the glomerular mesangium produce two characteristic lesions: AL-amyloidosis (AL-Am) and light chain deposition disease (LCDD). In both cases, the pathology is centered in the mesangium, where initial and progressive damage occurs. In AL-Am the mesangial matrix is destroyed and replaced by amyloid fibrils and in LCDD, the mesangial matrix is increased and remodeled. The collagen IV rich matrix is replaced by tenascin...
April 18, 2018: Ultrastructural Pathology
https://www.readbyqxmd.com/read/29659741/formin-2-regulates-lysosomal-degradation-of-wnt-associated-%C3%AE-catenin-in-neural-progenitors
#10
Gewei Lian, Anjen Chenn, Victor Ekuta, Sneha Kanaujia, Volney Sheen
Although neural progenitor proliferation along the ventricular zone is regulated by β-catenin through Wnt signaling, the cytoskeletal mechanisms that regulate expression and localization of these proteins are not well understood. Our prior studies have shown that loss of the actin-binding Filamin A (FlnA) and actin-nucleating protein Formin 2 (Fmn2) impairs endocytosis of low-density-lipoprotein-receptor-related protein 6 (Lrp6), thereby disrupting β-catenin activation, resulting in decreased brain size. Here, we report that activated RhoA-GTPase disengages Fmn2 N- to C-terminal binding to promote Fmn2 activation and redistribution into lysosomal vesicles...
April 5, 2018: Cerebral Cortex
https://www.readbyqxmd.com/read/29623762/degraded-melanocores-are-incompetent-to-protect-epidermal-keratinocytes-against-uv-damage
#11
Wen-Juan Yi, Meng-Yun Su, Ying Shi, Shan Jiang, Shi-Zheng Xu, Tie-Chi Lei
Melanosomes are membrane-bound intracellular organelles that are uniquely generated by melanocytes (MCs) in the basal layer of human epidermis. Highly pigmented mature melanosomes are transferred from melanocytes (MCs) to keratinocytes (KCs), and then positioned in the supra-nuclear region to ensure protection against ultraviolet radiation (UVR). However, the molecular mechanism underlying melanosome (or melanin pigment) transfer remains enigmatic. Emerging evidence shows that exo-/endo-cytosis of the melanosome core (termed melanocore) has been considered as the main transfer manner between MCs and KCs...
April 6, 2018: Cell Cycle
https://www.readbyqxmd.com/read/29622794/rab34-regulates-adhesion-migration-and-invasion-of-breast-cancer-cells
#12
Lixiang Sun, Xiaohui Xu, Yongjun Chen, Yuxia Zhou, Ran Tan, Hantian Qiu, Liting Jin, Wenyi Zhang, Rong Fan, Wanjin Hong, Tuanlao Wang
The small GTPase Rab34 regulates spatial distribution of the lysosomes, secretion, and macropinocytosis. In this study, we found that Rab34 is over-expressed in aggressive breast cancer cells, implying a potential role of Rab34 in breast cancer. Silencing Rab34 by shRNA inhibits cell migration, invasion, and adhesion of breast cancer cells. Rab34 specifically binds to the cytoplasmic tail of integrin β3, and depletion of Rab34 promotes the degradation of integrin β3. Interestingly, EGF induces the translocation of Rab34 to the membrane ruffle, which is greatly enhanced by the expression of Src kinase...
April 6, 2018: Oncogene
https://www.readbyqxmd.com/read/29573490/extracellular-matrix-internalization-links-nutrient-signalling-to-invasive-migration
#13
REVIEW
Elena Rainero
Integrins are the key mediators of cell-extracellular matrix (ECM) interaction, linking the ECM to the actin cytoskeleton. Besides localizing at the cell surface, they can be internalized and transported back to the plasma membrane (recycled) or delivered to the late endosomes/lysosomes for degradation. We and others have shown that integrin can be endocytosed together with their ECM ligands. In this short review, I will highlight how extracellular protein (including ECM) endocytosis impinges on the activation of the mechanistic target of rapamycin (mTOR) pathway, a master regulator of cell metabolism and growth...
March 24, 2018: International Journal of Experimental Pathology
https://www.readbyqxmd.com/read/29547664/overlapping-expression-patterns-and-functions-of-three-paralogous-p5b-atpases-in-caenorhabditis-elegans
#14
Jeffrey Zielich, Elena Tzima, Eva Ayla Schröder, Faten Jemel, Barbara Conradt, Eric J Lambie
P5B ATPases are present in the genomes of diverse unicellular and multicellular eukaryotes, indicating that they have an ancient origin, and that they are important for cellular fitness. Inactivation of ATP13A2, one of the four human P5B ATPases, leads to early-onset Parkinson's disease (Kufor-Rakeb Syndrome). The presence of an invariant PPALP motif within the putative substrate interaction pocket of transmembrane segment M4 suggests that all P5B ATPases might have similar transport specificity; however, the identity of the transport substrate(s) remains unknown...
2018: PloS One
https://www.readbyqxmd.com/read/29538296/sinomenine-hydrochloride-inhibits-the-metastasis-of-human-glioblastoma-cells-by-suppressing-the-expression-of-matrix-metalloproteinase-2-9-and-reversing-the-endogenous-and-exogenous-epithelial-mesenchymal-transition
#15
Yumao Jiang, Yue Jiao, Yang Liu, Meiyu Zhang, Zhiguo Wang, Yujuan Li, Tao Li, Xiaoliang Zhao, Danqiao Wang
As shown in our previous study, sinomenine hydrochloride (SH), the major bioactive alkaloid isolated from Sinomenium acutum Rehd. et Wils. (Fam. Menispermaceae ), initiates the autophagy-mediated death of human glioblastoma cells by generating reactive oxygen species and activating the autophagy-lysosome pathway. However, its effects on the migration and invasion of human glioblastoma cells have not yet been elucidated. Therefore, human glioblastoma U87 and SF767 cells were treated with SH (0.125 and 0.25 mM) for 24 h, and cell migration and invasion were assessed using scratch wound healing, migration and invasion assays...
March 14, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29467198/endothelial-tfeb-transcription-factor-eb-positively-regulates-postischemic-angiogenesis
#16
Yanbo Fan, Haocheng Lu, Wenying Liang, Minerva T Garcia-Barrio, Yanhong Guo, Ji Zhang, Tianqing Zhu, Yibai Hao, Jifeng Zhang, Y Eugene Chen
RATIONALE: Postischemic angiogenesis is critical to limit the ischemic tissue damage and improve the blood flow recovery. The regulation and the underlying molecular mechanisms of postischemic angiogenesis are not fully unraveled. TFEB (transcription factor EB) is emerging as a master gene for autophagy and lysosome biogenesis. However, the role of TFEB in vascular disease is less understood. OBJECTIVE: We aimed to determine the role of endothelial TFEB in postischemic angiogenesis and its underlying molecular mechanism...
March 30, 2018: Circulation Research
https://www.readbyqxmd.com/read/29464085/intravesicular-epidermal-growth-factor-receptor-subject-to-retrograde-trafficking-drives-epidermal-growth-factor-dependent-migration
#17
Sabrina Maisel, Derrick Broka, Joyce Schroeder
The Epidermal Growth Factor Receptor (EGFR) is frequently mutated and overexpressed in metastatic cancer. Although EGFR is a transmembrane tyrosine kinase localized to the basolateral membrane in normal epithelium, it is frequently found intracellularly localized in transformed cells. We have previously demonstrated the epithelial adaptor protein mucin 1 (MUC1) alters trafficking of EGFR, inhibiting its degradation and promoting its translocation to the nucleus, where it can directly modulate gene transcription...
January 19, 2018: Oncotarget
https://www.readbyqxmd.com/read/29455656/the-e3-ubiquitin-ligase-nedd4-mediates-cell-migration-signaling-of-egfr-in-lung-cancer-cells
#18
Genbao Shao, Ranran Wang, Aiqin Sun, Jing Wei, Ke Peng, Qian Dai, Wannian Yang, Qiong Lin
BACKGROUND: EGFR-dependent cell migration plays an important role in lung cancer progression. Our previous study observed that the HECT E3 ubiquitin ligase NEDD4 is significantly correlated with tumor metastasis and required for migration and invasion signaling of EGFR in gastric cancer cells. However, how NEDD4 promotes the EGFR-dependent lung cancer cell migration is unknown. This study is to elucidate the mechanism by which NEDD4 mediates the EGFR lung cancer migration signaling. METHODS: Lentiviral vector-loaded NEDD4 shRNA was used to deplete endogenous NEDD4 in lung cancer cell lines...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29444517/acetyl-coa-synthetase-2-promotes-cell-migration-and-invasion-of-renal-cell-carcinoma-by-upregulating-lysosomal-associated-membrane-protein-1-expression
#19
Lv Yao, Xiaoqiang Guo, Yaoting Gui
BACKGROUND/AIMS: Reprogramming energy metabolism is an emerging hallmark of many cancers, and this alteration is especially evident in renal cell carcinomas (RCCs). However, few studies have been conducted on lipid metabolism. This study investigated the function and mechanism of lipid metabolism-related acetyl-CoA synthetase 2 (ACSS2) in RCC development, cell migration and invasion. METHODS: Quantitative real-time PCR (qRT-PCR) was used to determine the expression of ACSS2 in cancer tissue and adjacent tissue...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29413706/photodynamic-effect-and-mechanism-study-of-selenium-enriched-phycocyanin-from-spirulina-platensis-against-liver-tumours
#20
Zijian Liu, Xiang Fu, Wei Huang, Chunxia Li, Xinyan Wang, Bei Huang
Selenium-containing phycocyanin (Se-PC) has been proved to have many biological effects, including anti-inflammatory and antioxidant. In this study, we investigated the photodynamic therapy (PDT) effects of Se-PC against liver tumour in vitro and in vivo experiment. Our results demonstrated that the half lethal dose of Se-PC PDT on HepG2 cells was 100μg/ml PC containing 20% selenium. Se-PC location migration from lysosomes to mitochondria was time dependent. In in vivo experiments, the tumour inhibition rate was 75...
March 2018: Journal of Photochemistry and Photobiology. B, Biology
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