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https://www.readbyqxmd.com/read/29352987/the-interaction-between-xbp1-and-enos-contributes-to-endothelial-cell-migration
#1
Junyao Yang, Jing Xu, Martin Danniel, Xiaocong Wang, Wen Wang, Lingfang Zeng, Lisong Shen
The X-box binding protein 1 (XBP1) is a pivotal transcription factor in the endoplasmic reticulum stress response. Our previous studies have proven that XBP1 is involved in vascular endothelial growth factor (VEGF)-mediated endothelial cell (EC) proliferation and angiogenesis. In this study, we used EC monolayer wound healing, tube formation and transwell migration models to explorethe role of XBP1splicing in EC migration. We found that scratching on EC monolayer triggered XBP1splicing, which was attenuated by the presence of SU5416and LY294002, suggesting that VEGF signalling pathways may be involved...
January 15, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29351849/the-dfm1-derlin-is-required-for-erad-retrotranslocation-of-integral-membrane-proteins
#2
Sonya Neal, Philipp A Jaeger, Sascha H Duttke, Christopher K Benner, Christopher Glass, Trey Ideker, Randolph Hampton
Endoplasmic reticulum (ER)-associated degradation (ERAD) removes misfolded proteins from the ER membrane and lumen by the ubiquitin-proteasome pathway. Retrotranslocation of ubiquitinated substrates to the cytosol is a universal feature of ERAD that requires the Cdc48 AAA-ATPase. Despite intense efforts, the mechanism of ER exit, particularly for integral membrane (ERAD-M) substrates, has remained unclear. Using a self-ubiquitinating substrate (SUS), which undergoes normal retrotranslocation independently of known ERAD factors, and the new SPOCK (single plate orf compendium kit) micro-library to query all yeast genes, we found the rhomboid derlin Dfm1 was required for retrotranslocation of both HRD and DOA ERAD pathway integral membrane substrates...
January 18, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29351844/interactome-screening-identifies-the-er-luminal-chaperone-hsp47-as-a-regulator-of-the-unfolded-protein-response-transducer-ire1%C3%AE
#3
Denisse Sepulveda, Diego Rojas-Rivera, Diego A Rodríguez, Jody Groenendyk, Andres Köhler, Cynthia Lebeaupin, Shinya Ito, Hery Urra, Amado Carreras-Sureda, Younis Hazari, Mireille Vasseur-Cognet, Maruf M U Ali, Eric Chevet, Gisela Campos, Patricio Godoy, Tomas Vaisar, Béatrice Bailly-Maitre, Kazuhiro Nagata, Marek Michalak, Jimena Sierralta, Claudio Hetz
Maintenance of endoplasmic reticulum (ER) proteostasis is controlled by a dynamic signaling network known as the unfolded protein response (UPR). IRE1α is a major UPR transducer, determining cell fate under ER stress. We used an interactome screening to unveil several regulators of the UPR, highlighting the ER chaperone Hsp47 as the major hit. Cellular and biochemical analysis indicated that Hsp47 instigates IRE1α signaling through a physical interaction. Hsp47 directly binds to the ER luminal domain of IRE1α with high affinity, displacing the negative regulator BiP from the complex to facilitate IRE1α oligomerization...
January 18, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29351515/understanding-key-mechanisms-of-exercise-induced-cardiac-protection-to-mitigate-disease-current-knowledge-and-emerging-concepts
#4
Bianca C Bernardo, Jenny Y Y Ooi, Kate L Weeks, Natalie L Patterson, Julie R McMullen
The benefits of exercise on the heart are well recognized, and clinical studies have demonstrated that exercise is an intervention that can improve cardiac function in heart failure patients. This has led to significant research into understanding the key mechanisms responsible for exercise-induced cardiac protection. Here, we summarize molecular mechanisms that regulate exercise-induced cardiac myocyte growth and proliferation. We discuss in detail the effects of exercise on other cardiac cells, organelles, and systems that have received less or little attention and require further investigation...
January 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29351168/co-regulation-of-er-stress-and-oxidative-stress-in-neuropathic-pain-and-disinhibition-of-the-spinal-nociceptive-circuitry
#5
Yanhu Ge, Yingfu Jiao, Peiying Li, Zhenghua Xiang, Zhi Li, Long Wang, Wenqian Li, Hao Gao, Jiayun Shao, Daxiang Wen, Weifeng Yu
The accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) lumen leads to ER stress, which is related to cellular reactive oxygen species (ROS) production. Neuropathic pain may result from spinal dorsal horn (SDH) ER stress. In this study, we examined the cause-effect relationship between ER stress and neuropathic pain using the spinal nerve ligation(SNL) rat model. We showed that ER stress was mutually promotive with oxidative stress during the process. We also tested the hypothesis that spinal sensitization arose from reduced activities of GABA-ergic interneurons and that spinal sensitization was mediated by SDH ER stress...
January 18, 2018: Pain
https://www.readbyqxmd.com/read/29350381/macrophage-migration-inhibitory-factor-knockout-attenuates-endotoxin-induced-cardiac-dysfunction-in-mice
#6
Jie Zhang, Xin Zhang, Yuqi Cui, Lianqun Cui, Peng Zhao
BACKGROUND: The accumulated evidence suggests that macrophage migration inhibitory factor (MIF) plays a key role not only in acute and chronic inflammatory diseases but also in cardiovascular disease. The cardiac dysfunction is related to lipopolysaccharide (LPS) in sepsis. AIM: This study was designed to examine whether MIF mediates LPS-induced cardiac dysfunction and address the mechanisms. METHODS: Echocardiography, immunohistochemical analysis, cell shortening/relengthening and intracellular Ca2+ fluorescence evaluation were performed in whole hearts and isolated cardiomyocytes from C57 and MIF knockout mice treated with or without LPS...
January 19, 2018: Kardiologia Polska
https://www.readbyqxmd.com/read/29350170/atypical-lower-motor-neuron-disease-with-enlargement-of-nissl-substance-report-of-an-autopsy-case
#7
Masayuki Shintaku, Daita Kaneda, Kiyomitsu Oyanagi
The patient was an 81-year-old woman diagnosed with atypical motor neuron disease who died after a long clinical course (7.5 years without mechanical assistance of ventilation) characterized by lower motor neuron signs and symptoms. Upper motor neuron signs and cognitive impairment were not apparent. Autopsy demonstrated severe neuronal loss in the anterior horn of the spinal cord, and some of the remaining neurons showed enlargement of Nissl substance and apparent thickening of the nuclear envelopes. No Bunina bodies, skein-like inclusions, or structures immunoreactive for phosphorylated transactivation response DNA-binding protein 43 were found...
January 19, 2018: Clinical Neuropathology
https://www.readbyqxmd.com/read/29349780/protective-effect-of-bled-exposed-conditioned-media-on-cell-injury
#8
Phil-Sun Oh, Eun-Mi Kim, Minjoo Kim, In Sun Kim, Yeon-Hee Han, SeokTae Lim, Myung-Hee Sohn, Myoung-Hwan Ko, Hwan-Jeong Jeong
Previous studies have reported that 450 nm blue light emitting diode (BLED) induces apoptosis through a mitochondria-mediated pathway in cancer cells and reduces the early stage tumor growth. The present study was performed to determine the effects of BLED-irradiated cell metabolites on cell injury. Our results showed that conditioned medium (CM) from cells irradiated with low-dose BLED (LCM) inhibited apoptosis and increased cell survival. Cell protection-related proteins were identified in cell metabolites of CM and LCM using 2-DE and MALDI-TOF analysis...
January 19, 2018: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/29348620/a-vacuolar-sorting-receptor-independent-sorting-mechanism-for-storage-vacuoles-in-soybean-seeds
#9
Nobuyuki Maruyama, Yuki Matsuoka, Kazunori Yokoyama, Kyoko Takagi, Tetsuya Yamada, Hisakazu Hasegawa, Teruhiko Terakawa, Masao Ishimoto
The seed storage proteins of soybean (Glycine max) are composed mainly of glycinin (11S globulin) and β-conglycinin (7S globulin). The subunits of glycinin (A1aB1b, A1bB2, A2B1a, A3B4, and A5A4B3) are synthesized as a single polypeptide precursor. These precursors are assembled into trimers with a random combination of subunits in the endoplasmic reticulum, and are sorted to the protein storage vacuoles. Proteins destined for transport to protein storage vacuoles possess a vacuolar sorting determinant, and in this regard, the A1aB1b subunit contains a C-terminal peptide that is sufficient for its sorting to protein storage vacuoles...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348619/cytokine-mediated-changes-in-k-channel-activity-promotes-an-adaptive-ca2-response-that-sustains-%C3%AE-cell-insulin-secretion-during-inflammation
#10
Matthew T Dickerson, Avery M Bogart, Molly K Altman, Sarah C Milian, Kelli L Jordan, Prasanna K Dadi, David A Jacobson
Cytokines present during low-grade inflammation contribute to β-cell dysfunction and diabetes. Cytokine signaling disrupts β-cell glucose-stimulated Ca2+ influx (GSCI) and endoplasmic reticulum (ER) Ca2+ ([Ca2+]ER) handling, leading to diminished glucose-stimulated insulin secretion (GSIS). However, cytokine-mediated changes in ion channel activity that alter β-cell Ca2+ handling remain unknown. Here we investigated the role of K+ currents in cytokine-mediated β-cell dysfunction. Kslow currents, which control the termination of intracellular Ca2+ ([Ca2+]i) oscillations, were reduced following cytokine exposure...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348607/evaluation-of-mitochondrial-bioenergetics-dynamics-endoplasmic-reticulum-mitochondria-crosstalk-and-reactive-oxygen-species-in-fibroblasts-from-patients-with-complex-i-deficiency
#11
Guilhian Leipnitz, Al-Walid Mohsen, Anuradha Karunanidhi, Bianca Seminotti, Vera Y Roginskaya, Desiree M Markantone, Mateus Grings, Stephanie J Mihalik, Peter Wipf, Bennett Van Houten, Jerry Vockley
Mitochondrial complex I (CI) deficiency is the most frequent cause of oxidative phosphorylation (OXPHOS) disorders in humans. In order to benchmark the effects of CI deficiency on mitochondrial bioenergetics and dynamics, respiratory chain (RC) and endoplasmic reticulum (ER)-mitochondria communication, and superoxide production, fibroblasts from patients with mutations in the ND6, NDUFV1 or ACAD9 genes were analyzed. Fatty acid metabolism, basal and maximal respiration, mitochondrial membrane potential, and ATP levels were decreased...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348368/defining-the-physiological-role-of-srp-in-protein-targeting-efficiency-and-specificity
#12
Elizabeth A Costa, Kelly Subramanian, Jodi Nunnari, Jonathan S Weissman
The signal recognition particle (SRP) enables cotranslational delivery of proteins for translocation into the endoplasmic reticulum (ER), but its full in vivo role remains incompletely explored. We combined rapid auxin-induced SRP degradation with proximity-specific ribosome profiling to define SRP's in vivo function in yeast. Despite the classic view that SRP recognizes N-terminal signal sequences, we show that SRP was generally essential for targeting transmembrane domains regardless of their position relative to the N terminus...
January 18, 2018: Science
https://www.readbyqxmd.com/read/29348267/toll-like-receptor-9-dependent-ampk%C3%AE-activation-occurs-via-tak1-and-contributes-to-rhoa-rock-signaling-and-actin-polymerization-in-vascular-smooth-muscle-cells
#13
Cameron G McCarthy, Camilla Ferreira Wenceslau, Safia Ogbi, Theodora Szasz, R Clinton Webb
Traditionally, Toll-like receptor (TLR)9 signals through a MyD88-dependent cascade that results in pro-inflammatory gene transcription. Recently it was reported that TLR9 also participates in a stress tolerance signaling cascade in non-immune cells. In this non-canonical pathway, TLR9 binds to and inhibits sarco/endoplasmic reticulum Ca2+-ATPase 2 (SERCA2), modulating intracellular calcium handling, and subsequently resulting in the activation of 5'-AMP-activated protein kinase (AMPK)α. We have previously reported TLR9 causes increased contraction in isolated arteries; however, the mechanisms underlying this vascular dysfunction need to be further clarified...
January 18, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29346549/transcriptome-and-functional-analysis-in-a-drosophila-model-of-ngly1-deficiency-provides-insight-into-therapeutic-approaches
#14
Katie G Owings, Joshua B Lowry, Yiling Bi, Matthew Might, Clement Y Chow
Autosomal recessive loss-of-function mutations in N-Glycanase 1 (NGLY1) cause NGLY1 deficiency, the only known human disease of deglycosylation. Patients present with developmental delay, movement disorder, seizures, liver dysfunction, and alacrima. NGLY1 is a conserved cytoplasmic component of the Endoplasmic Reticulum Associated Degradation (ERAD) pathway. ERAD clears misfolded proteins from the ER lumen. However, it is unclear how loss of NGLY1 function impacts ERAD and other cellular processes and results in the constellation of problems associated with NGLY1 deficiency...
January 15, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29346445/transcriptome-analysis-of-skin-fibroblasts-with-dominant-negative-col3a1-mutations-provides-molecular-insights-into-the-etiopathology-of-vascular-ehlers-danlos-syndrome
#15
Nicola Chiarelli, Giulia Carini, Nicoletta Zoppi, Marco Ritelli, Marina Colombi
Vascular Ehlers-Danlos syndrome (vEDS) is a dominantly inherited connective tissue disorder caused by mutations in the COL3A1 gene that encodes type III collagen (COLLIII), which is the major expressed collagen in blood vessels and hollow organs. The majority of disease-causing variants in COL3A1 are glycine substitutions and in-frame splice mutations in the triple helix domain that through a dominant negative effect are associated with the severe clinical spectrum potentially lethal of vEDS, characterized by fragility of soft connective tissues with arterial and organ ruptures...
2018: PloS One
https://www.readbyqxmd.com/read/29345572/breaking-the-dna-damage-response-via-serine-threonine-kinase-inhibitors-to-improve-cancer-treatment
#16
Wioletta Rozpedek, Dariusz Pytel, Alicja Nowak-Zdunczyk, Dawid Lewko, Radoslaw Wojtczak, John Alan Diehl, Ireneusz Majsterek
Multiple, both endogenous and exogenous, sources may induce DNA damage and DNA replication stress. Cells have developed DNA damage response (DDR) signaling pathways to maintain genomic stability and effectively detect and repair DNA lesions. Serine/threonine kinases such as Ataxia-telangiectasia mutated (ATM) and Ataxia-telangiectasia and Rad3-Related (ATR) are the major regulators of DDR, since after sensing stalled DNA replication forks, DNA double- or single-strand breaks, may directly phosphorylate and activate their downstream targets, that play a key role in DNA repair, cell cycle arrest and apoptotic cell death...
January 16, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29345463/-%C3%A2-sativamides-a-and-b-two-pairs-of-racemic-nor-lignanamide-enantiomers-from-the-fruits-of-cannabis-sativa-hemp-seed
#17
Guo-Yuan Zhu, Ji Yang, Xiao-Jun Yao, Xing Yang, Jing Fu, Xin Liu, Li-Ping Bai, Liang Liu, Zhi-Hong Jiang
(±)-Sativamides A (1) and B (2), two pairs of nor-lignanamide enantiomers featuring a unique benzo-angular triquinane skeleton, were isolated from the fruits of Cannabis sativa (hemp seed). Their structures were elucidated by detailed spectroscopic analysis and ECD calculations. The resolution of (+)- and (-)-sativamides A and B were achieved by chiral HPLC. Pretreatment of neuroblastoma cells with 1 and 2 significantly reduced the endoplasmic reticulum (ER) stress-induced cytotoxicity.
January 18, 2018: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29344723/structural-associations-between-organelle-membranes-in-nectary-parenchyma-cells
#18
Silvia Rodrigues Machado, Elisa A Gregório, Tatiane M Rodrigues
The close association between membranes and organelles, and the intense chloroplast remodeling in parenchyma cells of extrafloral nectaries occurred only at the secretion time and suggest a relationship with the nectar secretion. Associations between membranes and organelles have been well documented in different tissues and cells of plants, but poorly explored in secretory cells. Here, we described the close physical juxtaposition between membranes and organelles, mainly with chloroplasts, in parenchyma cells of Citharexylum myrianthum (Verbenaeceae) extrafloral nectaries under transmission electron microscopy, using conventional and microwave fixation...
January 17, 2018: Planta
https://www.readbyqxmd.com/read/29344665/overexpression-of-septin-7-inhibits-melatonin-induced-cell-apoptosis-in-human-fetal-osteoblastic-cells-via-suppression-of-endoplasmic-reticulum-stress
#19
Xiaotong Meng, Yue Zhu, Lin Tao, Sichao Zhao, Shui Qiu
Our previous study demonstrated that melatonin could induce apoptosis in the human fetal osteoblastic (hFOB) 1.19 cell line via induction of endoplasmic reticulum stress (ERS), and recent studies have demonstrated that the expression of septin‑7 (SEPT7) exhibits a positive correlation with the concentration of melatonin. Western blotting demonstrated the expression level of SEPT7 was significantly upregulated in a dose‑dependent manner following treatment with differing concentrations of melatonin compared with the control groups, which did not receive any treatment...
January 17, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29344638/garcinone-c-exerts-antitumor-activity-by-modulating-the-expression-of-atr-stat3-4e%C3%A2-bp1-in-nasopharyngeal-carcinoma-cells
#20
Yudui Xia, Xia Liu, Chunlin Zou, Shixiu Feng, Hongwei Guo, Yeguo Yang, Yong Lei, Jian Zhang, Yi Lu
Nasopharyngeal carcinoma (NPC) is one of the most common head and neck malignancies and is typically treated with radiotherapy and chemotherapy. Garcinone C, a natural compound isolated from Garcinia oblongifolia Champ., is a xanthone derivative with potential cytotoxic effects on certain cancers. However, there are limited studies regarding its effects on NPC cells, and its mechanism of action in NPC remains unknown. In the present study, we found that garcinone C significantly inhibited cell viability of the human NPC cell lines CNE1, CNE2, HK1 and HONE1...
January 16, 2018: Oncology Reports
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