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molecular chaperone and endoplasmic reticulum

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https://www.readbyqxmd.com/read/28315276/the-sigma-1-receptor-a-therapeutic-target-for-the-treatment-of-als
#1
Timur A Mavlyutov, Erin M Baker, Tasher M Losenegger, Jaimie R Kim, Brian Torres, Miles L Epstein, Arnold E Ruoho
The membrane bound 223 amino acid Sigma-1 Receptor (S1R) serves as a molecular chaperone and functional regulator of many signaling proteins. Spinal cord motor neuron activation occurs, in part, via large ventral horn cholinergic synapses called C-boutons/C-terminals. Chronic excitation of motor neurons and alterations in C-terminals has been associated with Amyotrophic Lateral Sclerosis (ALS ). The S1R has an important role in regulating motor neuron function. High levels of the S1R are localized in postsynaptic endoplasmic reticulum (ER) subsurface cisternae within 10-20 nm of the plasma membrane that contain muscarinic type 2 acetylcholine receptors (M2AChR), calcium activated potassium channels (Kv2...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28315273/stimulation-of-the-sigma-1-receptor-and-the-effects-on-neurogenesis-and-depressive-behaviors-in-mice
#2
Kohji Fukunaga, Shigeki Moriguchi
Sigma-1 receptor (Sig-1R) is molecular chaperone regulating calcium efflux from the neuronal endoplasmic reticulum to mitochondria. Recent studies show that Sig-1R stimulation antagonizes depressive-like behaviors in animal models, but molecular mechanisms underlying this effect remain unclear. Here, we focus on the effects of Sig-1R ligands on hippocampal neurogenesis and depressive-like behaviors. Sig-1R stimulation also enhances CaMKII /CaMKIV and protein kinase B (Akt) activities in hippocampus. Therefore, we discuss the fundamental roles of Sig-1R, CaMKII /CaMKIV and protein kinase B (Akt) signaling in amelioration of depressive-like behaviors following Sig-1R stimulation...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28315269/sigma-1-receptors-and-neurodegenerative-diseases-towards-a-hypothesis-of-sigma-1-receptors-as-amplifiers-of-neurodegeneration-and-neuroprotection
#3
Linda Nguyen, Brandon P Lucke-Wold, Shona Mookerjee, Nidhi Kaushal, Rae R Matsumoto
Sigma-1 receptors are molecular chaperones that may act as pathological mediators and targets for novel therapeutic applications in neurodegenerative diseases. Accumulating evidence indicates that sigma-1 ligands can either directly or indirectly modulate multiple neurodegenerative processes, including excitotoxicity, calcium dysregulation, mitochondrial and endoplasmic reticulum dysfunction, inflammation, and astrogliosis. In addition, sigma-1 ligands may act as disease-modifying agents in the treatment for central nervous system (CNS) diseases by promoting the activity of neurotrophic factors and neural plasticity...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28303141/the-function-of-fk506-binding-protein-13-in-protein-quality-control-protects-plasma-cells-from-endoplasmic-reticulum-stress-associated-apoptosis
#4
Mini Jeong, Eunkyeong Jang, Suk San Choi, Changhoon Ji, Kyungho Lee, Jeehee Youn
Plasma cells (PCs) are exposed to intense endoplasmic reticulum (ER) stress imposed by enormous rates of immunoglobulin (Ig) synthesis and secretion. Therefore, protein homeostasis is crucial for the survival of PCs, but its molecular mechanism remains largely unknown. Here, we found marked overexpression of FK506-binding protein 13 (FKBP13) in long-lived PCs from autoimmune mice and investigated its function using a plasmacytoma cell line secreting IgA. FKBP13 expression was induced largely in the lumen of ER in response to treatment with an ER stressor tunicamycin or overexpression of an adaptive unfolded protein response (UPR) protein X-box binding protein 1 (XBP1)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28286085/hspa5-gene-encoding-hsp70-chaperone-bip-in-the-endoplasmic-reticulum
#5
REVIEW
Jie Wang, Jessica Lee, David Liem, Peipei Ping
The HSPA5 gene (Ensembl ID: ENSG00000044574 (WTSI/EMBL-EBI, 2015)) encodes the binding immunoglobulin protein (BiP), an Hsp70 family chaperone localized in the ER lumen. As a highly conserved molecular chaperone, BiP assists in a wide range of folding processes via its two structural domains, a nucleotide-binding domain (NBD) and substrate-binding domain (SBD). BiP is also an essential component of the translocation machinery for protein import into the ER, a regulator for Ca(2+) homeostasis in the ER, as well as a facilitator of ER-associated protein degradation (ERAD) via retrograde transportation of aberrant proteins across the ER membrane...
March 7, 2017: Gene
https://www.readbyqxmd.com/read/28285140/analysis-of-the-potency-of-various-low-molecular-weight-chemical-chaperones-to-prevent-protein-aggregation
#6
Chandak Upagupta, Rachel E Carlisle, Jeffrey G Dickhout
Newly translated proteins must undergo proper folding to ensure their function. To enter a low energy state, misfolded proteins form aggregates, which are associated with many degenerative diseases, such as Huntington's disease and chronic kidney disease (CKD). Recent studies have shown the use of low molecular weight chemical chaperones to be an effective method of reducing protein aggregation in various cell types. This study demonstrates a novel non-biased assay to assess the molecular efficacy of these compounds at preventing protein misfolding and/or aggregation...
March 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28257787/red-ox-states-of-human-protein-disulfide-isomerase-regulate-binding-affinity-of-17-beta-estradiol
#7
Razieh Karamzadeh, Mohammad Hossein Karimi-Jafari, Ali Akbar Saboury, Ghasem Hosseini Salekdeh, Ali Akbar Moosavi-Movahedi
Human protein disulfide isomerase (hPDI) is a key redox-regulated thiol-containing protein operating as both oxidoreductase and molecular chaperone in the endoplasmic reticulum of cells. hPDI thiol-disulfide interchange reactions lead to the adoption of two distinct red/ox conformations with different substrate preferences. hPDI also displays high binding capacity for some endogenous steroid hormones including 17 beta-estradiol (E2) and thus contributes to the regulation of their intracellular concentration, storage and actions...
February 28, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28257000/an-unexpected-role-for-the-yeast-nucleotide-exchange-factor-sil1-as-a-reductant-acting-on-the-molecular-chaperone-bip
#8
Kevin D Siegenthaler, Kristeen A Pareja, Jie Wang, Carolyn S Sevier
Unfavorable redox conditions in the endoplasmic reticulum (ER) can decrease the capacity for protein secretion, altering vital cell functions. While systems to manage reductive stress are well-established, how cells cope with an overly oxidizing ER remains largely undefined. In previous work (Wang et al., 2014), we demonstrated that the chaperone BiP is a sensor of overly oxidizing ER conditions. We showed that modification of a conserved BiP cysteine during stress beneficially alters BiP chaperone activity to cope with suboptimal folding conditions...
March 3, 2017: ELife
https://www.readbyqxmd.com/read/28252521/alzheimer-s-disease-pathology-and-the-unfolded-protein-response-prospective-pathways-and-therapeutic-targets
#9
David J Koss, Bettina Platt
Many vital interdependent cellular functions including proteostasis, lipogenesis and Ca homeostasis are executed by the endoplasmic reticulum (ER). Exogenous insults can impair ER performance: this must be rapidly corrected or cell death will ensue. Protective adaptations can boost the functional capacity of the ER and form the basis of the unfolded protein response (UPR). Activated in response to the accumulation of misfolded proteins, the UPR can halt protein translation while increasing protein-handling chaperones and the degradation of erroneous proteins through a conserved three-tier molecular cascade...
April 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28250763/molecular-chaperones-and-hypoxic-ischemic-encephalopathy
#10
REVIEW
Cong Hua, Wei-Na Ju, Hang Jin, Xin Sun, Gang Zhao
Hypoxic-ischemic encephalopathy (HIE) is a disease that occurs when the brain is subjected to hypoxia, resulting in neuronal death and neurological deficits, with a poor prognosis. The mechanisms underlying hypoxic-ischemic brain injury include excitatory amino acid release, cellular proteolysis, reactive oxygen species generation, nitric oxide synthesis, and inflammation. The molecular and cellular changes in HIE include protein misfolding, aggregation, and destruction of organelles. The apoptotic pathways activated by ischemia and hypoxia include the mitochondrial pathway, the extrinsic Fas receptor pathway, and the endoplasmic reticulum stress-induced pathway...
January 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28238527/interferon-alpha-impairs-insulin-production-in-human-beta-cells-via-endoplasmic-reticulum-stress
#11
Angela Lombardi, Yaron Tomer
Despite substantial advances in the research exploring the pathogenesis of Type 1 Diabetes (T1D), the pathophysiological mechanisms involved remain unknown. We hypothesized in this study that interferon alpha (IFNα) participates in the early stages of T1D development by triggering endoplasmic reticulum (ER) stress. To verify our hypothesis, human islets and human EndoC-βH1 cells were exposed to IFNα and tested for ER stress markers, glucose stimulated insulin secretion (GSIS) and insulin content. IFNα treatment induced upregulation of ER stress markers including Binding immunoglobulin Protein, phospho-eukaryotic translation initiation factor 2α, spliced- X-box binding protein-1, C/EBP homologous protein and activating transcription factor 4...
February 23, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28228754/proofreading-of-peptide-mhc-complexes-through-dynamic-multivalent-interactions
#12
REVIEW
Christoph Thomas, Robert Tampé
The adaptive immune system is able to detect and destroy cells that are malignantly transformed or infected by intracellular pathogens. Specific immune responses against these cells are elicited by antigenic peptides that are presented on major histocompatibility complex class I (MHC I) molecules and recognized by cytotoxic T lymphocytes at the cell surface. Since these MHC I-presented peptides are generated in the cytosol by proteasomal protein degradation, they can be metaphorically described as a window providing immune cells with insights into the state of the cellular proteome...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28190459/mutations-in-inpp5k-cause-a-form-of-congenital-muscular-dystrophy-overlapping-marinesco-sj%C3%A3-gren-syndrome-and-dystroglycanopathy
#13
Daniel P S Osborn, Heather L Pond, Neda Mazaheri, Jeremy Dejardin, Christopher J Munn, Khaloob Mushref, Edmund S Cauley, Isabella Moroni, Maria Barbara Pasanisi, Elizabeth A Sellars, R Sean Hill, Jennifer N Partlow, Rebecca K Willaert, Jaipreet Bharj, Reza Azizi Malamiri, Hamid Galehdari, Gholamreza Shariati, Reza Maroofian, Marina Mora, Laura E Swan, Thomas Voit, Francesco J Conti, Yalda Jamshidi, M Chiara Manzini
Congenital muscular dystrophies display a wide phenotypic and genetic heterogeneity. The combination of clinical, biochemical, and molecular genetic findings must be considered to obtain the precise diagnosis and provide appropriate genetic counselling. Here we report five individuals from four families presenting with variable clinical features including muscular dystrophy with a reduction in dystroglycan glycosylation, short stature, intellectual disability, and cataracts, overlapping both the dystroglycanopathies and Marinesco-Sjögren syndrome...
March 2, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28167764/hy5-a-positive-regulator-of-light-signaling-negatively-controls-the-unfolded-protein-response-in-arabidopsis
#14
Ganesh M Nawkar, Chang Ho Kang, Punyakishore Maibam, Joung Hun Park, Young Jun Jung, Ho Byoung Chae, Yong Hun Chi, In Jung Jung, Woe Yeon Kim, Dae-Jin Yun, Sang Yeol Lee
Light influences essentially all aspects of plant growth and development. Integration of light signaling with different stress response results in improvement of plant survival rates in ever changing environmental conditions. Diverse environmental stresses affect the protein-folding capacity of the endoplasmic reticulum (ER), thus evoking ER stress in plants. Consequently, the unfolded protein response (UPR), in which a set of molecular chaperones is expressed, is initiated in the ER to alleviate this stress...
February 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28112451/calreticulin-is-a-fine-tuning-molecule-in-epibrassinolide-induced-apoptosis-through-activating-endoplasmic-reticulum-stress-in-colon-cancer-cells
#15
Pinar Obakan-Yerlikaya, Elif Damla Arisan, Ajda Coker-Gurkan, Kaan Adacan, Utku Özbey, Berna Somuncu, Didem Baran, Narçin Palavan-Ünsal
Epibrassinolide (EBR), a member of brassinostreoids plant hormones with cell proliferation promoting role in plants, is a natural polyhydroxysteroid with structural similarity to steroid hormones of vertebrates. EBR has antiproliferative and apoptosis-inducing effect in various cancer cells. Although EBR has been shown to affect survival and mitochondria-mediated apoptosis pathways in a p53-independent manner, the exact molecular targets of EBR are still under investigation. Our recent SILAC (Stable Isotope Labeling by Amino Acids in Cell Culture) data showed that the most significantly altered protein after EBR treatment was calreticulin (CALR)...
January 23, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28079009/emerging-roles-of-calreticulin-in-cancer-implications-for-therapy
#16
Kavya Venkateswaran, Amit Verma, Anant Narayan Bhatt, Anju Shrivastava, Kailash Manda, Hanumantharao G Raj, Ashok Prasad, Christophe Len, Virinder S Parmar, Bilikere Dwarakanath
Calreticulin (CRT), initially identified as a ubiquitous calcium-binding protein in the endoplasmic reticulum, has emerged as a multifunctional protein with roles in calcium homeostasis, molecular chaperoning and cell adhesion. Emerging evidence suggests its involvement in tumorigenesis facilitating proliferation, migration, and adhesion. CRT translocated to the cell surface (ecto-CRT) serves as a phagocytic signal for immunogenic cell death (ICD) mediated through dendritic cells (DCs) and cytotoxic T-cell activation thereby making tumors susceptible to immunotherapy-based anti-cancer strategies...
January 11, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28069662/endoplasmic-reticulum-stress-inhibition-limits-the-progression-of-chronic-kidney-disease-in-the-dahl-salt-sensitive-rat
#17
Victoria Yum, Rachel E Carlisle, Chao Lu, Elise Brimble, Jasmine Chahal, Chandak Upagupta, Kjetil Ask, Jeffrey G Dickhout
Proteinuria is one of the primary risk factors for the progression of chronic kidney disease (CKD) and has been implicated in the induction of endoplasmic reticulum (ER) stress. We hypothesized that the suppression of ER stress with a low molecular weight chemical chaperone, 4-phenylbutyric acid (4-PBA), would reduce the severity of CKD and proteinuria in the Dahl salt-sensitive (SS) hypertensive rat. To induce hypertension and CKD, 12-wk-old male rats were placed on a high-salt (HS) diet for 4 wk with or without 4-PBA treatment...
January 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28032645/arabidopsis-b-cell-lymphoma2-bcl-2-associated-athanogene-7-bag7-mediated-heat-tolerance-requires-translocation-sumoylation-and-binding-to-wrky29
#18
Yurong Li, Brett Williams, Martin Dickman
To cope with stress and increased accumulation of misfolded proteins, plants and animals use a survival pathway known as the unfolded protein response (UPR) that signals between the endoplasmic reticulum (ER) and the nucleus to maintain cell homeostasis via proper folding of proteins. B-cell lymphoma2 (Bcl-2)-associated athanogene (BAG) proteins are an evolutionarily conserved family of co-chaperones that are linked to disease states in mammals and responses to environmental stimuli (biotic and abiotic) in plants...
December 29, 2016: New Phytologist
https://www.readbyqxmd.com/read/28028229/achromatopsia-mutations-target-sequential-steps-of-atf6-activation
#19
Wei-Chieh Chiang, Priscilla Chan, Bernd Wissinger, Ajoy Vincent, Anna Skorczyk-Werner, Maciej R Krawczyński, Randal J Kaufman, Stephen H Tsang, Elise Héon, Susanne Kohl, Jonathan H Lin
Achromatopsia is an autosomal recessive disorder characterized by cone photoreceptor dysfunction. We recently identified activating transcription factor 6 (ATF6) as a genetic cause of achromatopsia. ATF6 is a key regulator of the unfolded protein response. In response to endoplasmic reticulum (ER) stress, ATF6 migrates from the ER to Golgi to undergo regulated intramembrane proteolysis to release a cytosolic domain containing a basic leucine zipper (bZIP) transcriptional activator. The cleaved ATF6 fragment migrates to the nucleus to transcriptionally up-regulate protein-folding enzymes and chaperones...
January 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28028074/chaperone-driven-degradation-of-a-misfolded-proinsulin-mutant-in-parallel-with-restoration-of-wild-type-insulin-secretion
#20
Corey N Cunningham, Kaiyu He, Anoop Arunagiri, Adrienne W Paton, James C Paton, Peter Arvan, Billy Tsai
In heterozygous patients with a diabetic syndrome called mutant INS gene-induced diabetes of youth (MIDY), there is decreased insulin secretion when mutant proinsulin expression prevents wild-type (WT) proinsulin from exiting the endoplasmic reticulum (ER), which is essential for insulin production. Our previous results revealed that mutant Akita proinsulin is triaged by ER-associated degradation (ERAD). We now find that the ER chaperone Grp170 participates in the degradation process by shifting Akita proinsulin from high-molecular weight (MW) complexes toward smaller oligomeric species that are competent to undergo ERAD...
March 2017: Diabetes
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