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molecular chaperone and endoplasmic reticulum

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https://www.readbyqxmd.com/read/28811106/questiomycin-a-stimulates-sorafenib-induced-cell-death-via-suppression-of-glucose-regulated-protein-78
#1
Kayo Machihara, Hidenori Tanaka, Yoshihiro Hayashi, Ichiro Murakami, Takushi Namba
Hepatocellular carcinoma (HCC) is one of the most difficult cancers to treat owing to the lack of effective chemotherapeutic methods. Sorafenib, the first-line and only available treatment for HCC, extends patient overall survival by several months, with a response rate below 10%. Thus, the identification of an agent that enhances the anticancer effect of sorafenib is critical for the development of therapeutic options for HCC. Endoplasmic reticulum (ER) stress response is one of the methods of sorafenib-induced cell death...
August 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28802884/astrocytes-and-endoplasmic-reticulum-stress-a-bridge-between-obesity-and-neurodegenerative-diseases
#2
REVIEW
Cynthia A Martin-Jiménez, Ángela García-Vega, Ricardo Cabezas, Gjumrakch Aliev, Valentina Echeverria, Janneth González, George E Barreto
Endoplasmic reticulum (ER) is a subcellular organelle involved in protein folding and processing. ER stress constitutes a cellular process characterized by accumulation of misfolded proteins, impaired lipid metabolism and induction of inflammatory responses. ER stress has been suggested to be involved in several human pathologies, including neurodegenerative diseases and obesity. Different studies have shown that both neurodegenerative diseases and obesity trigger similar cellular responses to ER stress. Moreover, both diseases are assessed in astrocytes as evidences suggest these cells as key regulators of brain homeostasis...
August 9, 2017: Progress in Neurobiology
https://www.readbyqxmd.com/read/28801701/the-overexpression-of-hsp90b1-is-associated-with-tumorigenesis-of-canine-mammary-glands
#3
B V Sunil Kumar, Rabia Bhardwaj, Kanika Mahajan, Neeraj Kashyap, Ashwani Kumar, Ramneek Verma
Heat shock proteins (Hsp) are molecular chaperones that are responsible for protein folding and maintenance of cellular homeostasis. Hsp90, an important member of HSP family, has an important role in breast cancer. Glucose-regulated protein 94 (Grp94) is the endoplasmic reticulum paralog of Hsp90 encoded by Hsp90B1 gene. To test if this protein is overexpressed in dogs with mammary tumor, we estimated and compared its serum levels in healthy dogs and that of dogs with mammary tumors. Hsp90B1 mRNA expression was measured in tumorous and healthy mammary tissues (from age- and breed-matched dogs) by real-time PCR...
August 12, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28801645/chronic-intermittent-hypobaric-hypoxia-improves-cardiac-function-through-inhibition-of-endoplasmic-reticulum-stress
#4
Fang Yuan, Li Zhang, Yan-Qing Li, Xu Teng, Si-Yu Tian, Xiao-Ran Wang, Yi Zhang
We investigated the role of endoplasmic reticulum stress (ERS) in chronic intermittent hypobaric hypoxia (CIHH)-induced cardiac protection. Adult male Sprague-Dawley rats were exposed to CIHH treatment simulating 5000 m altitude for 28 days, 6 hours per day. The heart was isolated and perfused with Langendorff apparatus and subjected to 30-min ischemia followed by 60-min reperfusion. Cardiac function, infarct size, and lactate dehydrogenase (LDH) activity were assessed. Expression of ERS molecular chaperones (GRP78, CHOP and caspase-12) was assayed by western blot analysis...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28794819/upregulation-of-autophagy-genes-and-the-unfolded-protein-response-in-human-heart-failure
#5
Brian C Jensen, Scott J Bultman, Darcy Holley, Wei Tang, Gustaaf de Ridder, Salvatore Pizzo, Dawn Bowles, Monte S Willis
The cellular environment of the mammalian heart constantly is challenged with environmental and intrinsic pathological insults, which affect the proper folding of proteins in heart failure. The effects of damaged or misfolded proteins on the cell can be profound and result in a process termed "proteotoxicity". While proteotoxicity is best known for its role in mediating the pathogenesis of neurodegenerative diseases such as Alzheimer's disease, its role in human heart failure also has been recognized. The UPR involves three branches, including PERK, ATF6, and IRE1...
2017: International Journal of Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/28769758/the-role-of-bip-retrieval-by-the-kdel-receptor-in-the-early-secretory-pathway-and-its-effect-on-protein-quality-control-and-neurodegeneration
#6
REVIEW
Hisayo Jin, Mari Komita, Tomohiko Aoe
Protein quality control in the early secretory pathway is a ubiquitous eukaryotic mechanism for adaptation to endoplasmic reticulum (ER) stress. An ER molecular chaperone, immunoglobulin heavy chain-binding protein (BiP), is one of the essential components in this process. BiP interacts with nascent proteins to facilitate their folding. BiP also plays an important role in preventing aggregation of misfolded proteins and regulating the ER stress response when cells suffer various injuries. BiP is a member of the 70-kDa heat shock protein (HSP70) family of molecular chaperones that resides in the ER...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28768768/regulation-of-the-epithelial-na-channel-by-paraoxonase-2
#7
Shujie Shi, Teresa M Buck, Carol L Kinlough, Allison L Marciszyn, Rebecca P Hughey, Martin Chalfie, Jeffrey L Brodsky, Thomas R Kleyman
Paraoxonase-2 (PON-2) is a membrane-bound lactonase with unique anti-oxidative and anti-atherosclerotic properties. PON-2 shares key structural elements with MEC-6, an endoplasmic reticulum resident molecular chaperone in Caenorhabditis elegans MEC-6 modulates the expression of a mechano-transductive ion channel comprised of MEC-4 and MEC-10 in touch receptor neurons. Because pon-2 mRNA resides in multiple rat nephron segments, including aldosterone-sensitive distal nephron where the epithelial Na(+) channel (ENaC) is expressed, we hypothesized that PON-2 would similarly regulate ENaC expression...
August 2, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28768697/a-novel-high-throughput-yeast-genetic-screen-for-factors-modifying-protein-levels-of-the-early-onset-torsion-dystonia-associated-variant-torsina%C3%AE-e
#8
Lucía F Zacchi, John C Dittmar, Michael J Mihalevic, Annette M Shewan, Benjamin L Schulz, Jeffrey L Brodsky, Kara A Bernstein
Dystonia is the third most common movement disorder, but its diagnosis and treatment remain challenging. One of the most severe types of Dystonia is Early-Onset Torsion Dystonia (EOTD). The best studied and validated EOTD-associated mutation, torsinAΔE, is a deletion of a C-terminal glutamate residue in the AAA+ ATPase, torsinA. TorsinA appears to be an Endoplasmic Reticulum (ER)/Nuclear Envelope chaperone with multiple roles in the secretory pathway and in determining subcellular architecture. Many functions are disabled in the torsinAΔE variant, and torsinAΔE is also less stable than wild-type torsinA and is a substrate for ER-associated degradation...
August 2, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28736525/pharmaceutical-chaperones-and-proteostasis-regulators-in-the-therapy-of-lysosomal-storage-disorders-current-perspective-and-future-promises
#9
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/28707656/-regulation-of-heat-shock-gene-expression-in-response-to-stress
#10
D G Garbuz
Heat shock (HS) genes, or stress genes, code for a number of proteins that collectively form the most ancient and universal stress defense system. The system determines the cell capability of adaptation to various adverse factors and performs a variety of auxiliary functions in normal physiological conditions. Common stress factors, such as higher temperatures, hypoxia, heavy metals, and others, suppress transcription and translation for the majority of genes, while HS genes are upregulated. Transcription of HS genes is controlled by transcription factors of the HS factor (HSF) family...
May 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28706332/role-of-elsholtzia-communis-in-counteracting-stress-by-modulating-expression-of-hspa14-c-ebp-homologous-protein-nuclear-factor-erythroid-derived-2-like-2-factor-caspase-3-and-brain-derived-neurotrophic-factor-in-rat-hippocampus
#11
Chandana Choudhury Barua, Pompy Patowary, Arundhati Purkayastha, Prakash Haloi, Manab Jyoti Bordoloi
OBJECTIVE: Elsholtzia communis (Collett and Hemsl.) Diels has been widely distributed and is reported for many therapeutic effects. The present study aims to investigate the antistress activity of the leaf extract and its possible molecular mechanism. MATERIALS AND METHODS: Hydroethanolic extract of leaves of E. communis (100 and 200 mg/kg, p.o.) were administered for 7 days to stress-induced male Wistar rats. The experimental animals were divided into five groups (n = 6)...
March 2017: Indian Journal of Pharmacology
https://www.readbyqxmd.com/read/28706146/ros-independent-nrf2-activation-in-prostate-cancer
#12
Ilaria Bellezza, Paolo Scarpelli, Salvatore V Pizzo, Silvia Grottelli, Egidia Costanzi, Alba Minelli
In prostate cancer, oxidative stress and the subsequent Nrf2 activation promote the survival of cancer cells and acquired chemoresistance. Nrf2 links prostate cancer to endoplasmic reticulum stress, an event that triggers the unfolded protein response, aiming to restore cellular homeostasis as well as an adaptive survival mechanism. Glucose-regulated protein of 78 kD /immunoglobulin heavy chain binding protein (GRP78/BiP) is a key molecular chaperone in the endoplasmic reticulum that, when expressed at the cell surface, acts as a receptor for several signaling pathways enhancing antiapoptotic and proliferative signals...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28667477/allosteric-modulation-of-opioid-g-protein-coupled-receptors-by-sigma1-receptors
#13
Gavril W Pasternak
Since their proposal in 1976, the concept of sigma1 receptors has been continually evolving. Initially thought to be a member of the opioid receptor family, molecular studies have now identified its genes and established its structure crystallographically. Much effort has now revealed its importance as a chaperone in the endoplasmic reticulum, but its functions extend beyond this. Sigma1 receptors have been associated with a host of signaling systems. Evidence over the past 20 years has established the modulatory effects of sigma1 ligands on opioid systems...
July 1, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28646128/%C3%AE-copi-mediates-the-retention-of-kae1-g701d-protein-in-golgi-apparatus-a-mechanistic-explanation-of-distal-renal-tubular-acidosis-associated-with-the-g701d-mutation
#14
Natapol Duangtum, Mutita Junking, Suratchanee Phadngam, Nunghathai Sawasdee, Andrea Castiglioni, Komgrid Charngkaew, Thawornchai Limjindaporn, Ciro Isidoro, Pa-Thai Yenchitsomanus
Mutations of the solute carrier family 4 member 1 (SLC4A1) gene encoding kidney anion (chloride/bicarbonate ion) exchanger 1 (kAE1) can cause genetic distal renal tubular acidosis (dRTA). Different SLC4A1 mutations give rise to mutant kAE1 proteins with distinct defects in protein trafficking. The mutant kAE1 protein may be retained in endoplasmic reticulum (ER) or Golgi apparatus, or mis-targeted to the apical membrane, failing to display its function at the baso-lateral membrane. The ER-retained mutant kAE1 interacts with calnexin chaperone protein; disruption of this interaction permits the mutant kAE1 to reach the cell surface and display anion exchange activity...
July 17, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28642246/modulation-of-endoplasmic-reticulum-stress-controls-cd4-t-cell-activation-and-antitumor-function
#15
Jessica E Thaxton, Caroline Wallace, Brian Riesenberg, Yongliang Zhang, Chrystal M Paulos, Craig C Beeson, Bei Liu, Zihai Li
The endoplasmic reticulum (ER) is an energy-sensing organelle with intimate ties to programming cell activation and metabolic fate. T-cell receptor (TCR) activation represents a form of acute cell stress and induces mobilization of ER Ca(2+) stores. The role of the ER in programming T-cell activation and metabolic fate remains largely undefined. Gp96 is an ER protein with functions as a molecular chaperone and Ca(2+) buffering protein. We hypothesized that the ER stress response may be important for CD4(+) T-cell activation and that gp96 may be integral to this process...
August 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28622300/the-als-linked-e102q-mutation-in-sigma-receptor-1-leads-to-er-stress-mediated-defects-in-protein-homeostasis-and-dysregulation-of-rna-binding-proteins
#16
Alice Dreser, Jan Tilmann Vollrath, Antonio Sechi, Sonja Johann, Andreas Roos, Alfred Yamoah, Istvan Katona, Saeed Bohlega, Dominik Wiemuth, Yuemin Tian, Axel Schmidt, Jörg Vervoorts, Marc Dohmen, Cordian Beyer, Jasper Anink, Eleonora Aronica, Dirk Troost, Joachim Weis, Anand Goswami
Amyotrophic lateral sclerosis (ALS) is characterized by the selective degeneration of motor neurons (MNs) and their target muscles. Misfolded proteins which often form intracellular aggregates are a pathological hallmark of ALS. Disruption of the functional interplay between protein degradation (ubiquitin proteasome system and autophagy) and RNA-binding protein homeostasis has recently been suggested as an integrated model that merges several ALS-associated proteins into a common pathophysiological pathway...
June 16, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28622297/p53-mediated-suppression-of-bip-triggers-bik-induced-apoptosis-during-prolonged-endoplasmic-reticulum-stress
#17
Ignacio López, Anne-Sophie Tournillon, Rodrigo Prado Martins, Konstantinos Karakostis, Laurence Malbert-Colas, Karin Nylander, Robin Fåhraeus
Physiological and pathological conditions that affect the folding capacity of the endoplasmic reticulum (ER) provoke ER stress and trigger the unfolded protein response (UPR). The UPR aims to either restore the balance between newly synthesized and misfolded proteins or if the damage is severe, to trigger cell death. However, the molecular events underlying the switch between repair and cell death are not well understood. The ER-resident chaperone BiP governs the UPR by sensing misfolded proteins and thereby releasing and activating the three mediators of the UPR: PERK, IRE1 and ATF6...
June 16, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28603497/sigma-1-receptor-plays-a-negative-modulation-on-n-type-calcium-channel
#18
Kang Zhang, Zhe Zhao, Liting Lan, Xiaoli Wei, Liyun Wang, Xiaoyan Liu, Haitao Yan, Jianquan Zheng
The sigma-1 receptor is a 223 amino acids molecular chaperone with a single transmembrane domain. It is resident to eukaryotic mitochondrial-associated endoplasmic reticulum and plasma membranes. By chaperone-mediated interactions with ion channels, G-protein coupled receptors and cell-signaling molecules, the sigma-1 receptor performs broad physiological and pharmacological functions. Despite sigma-1 receptors have been confirmed to regulate various types of ion channels, the relationship between the sigma-1 receptor and N-type Ca(2+) channel is still unclear...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28598856/glucocerebrosidase-mutations-in-parkinson-disease
#19
Grace O'Regan, Ruth-Mary deSouza, Roberta Balestrino, Anthony H Schapira
Following the discovery of a higher than expected incidence of Parkinson Disease (PD) in Gaucher disease, a lysosomal storage disorder, mutations in the glucocerebrocidase (GBA) gene, which encodes a lysosomal enzyme involved in sphingolipid degradation were explored in the context of idiopathic PD. GBA mutations are now known to be the single largest risk factor for development of idiopathic PD. Clinically, on imaging and pharmacologically, GBA PD is almost identical to idiopathic PD, other than certain features that can be identified in the specialist research setting but not in routine clinical practice...
2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28586043/grp78-silencing-enhances-hyperoxia-induced-alveolar-epithelial-cell-apoptosis-via-chop-pathway
#20
Hong-Yan Lu, Xiao-Qing Chen, Wei Tang, Qiu-Xia Wang, Jie Zhang
Hyperoxia is one of the primary causes of bronchopulmonary dysplasia, which may occur in premature infants following supplemental oxygen therapy. Glucose regulated protein 78 (GRP78), which is a molecular chaperone located in the lumen of the endoplasmic reticulum (ER), has been reported to regulate hyperoxia‑associated ER stress. The role of GRP78 in lung epithelial cells during hyperoxia remains to be elucidated. In the present study, the A549 cultured human lung epithelial cell line was exposed to hyperoxic conditions, and then transfected with short interfering (si)RNA targeted to GRP78...
August 2017: Molecular Medicine Reports
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