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Cytosolic AND pH

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https://www.readbyqxmd.com/read/30540949/ip-3-receptors-preferentially-associate-with-er-lysosome-contact-sites-and-selectively-deliver-ca-2-to-lysosomes
#1
Peace Atakpa, Nagendra Babu Thillaiappan, Stefania Mataragka, David L Prole, Colin W Taylor
Inositol 1,4,5-trisphosphate (IP3 ) receptors (IP3 Rs) allow extracellular stimuli to redistribute Ca2+ from the ER to cytosol or other organelles. We show, using small interfering RNA (siRNA) and vacuolar H+ -ATPase (V-ATPase) inhibitors, that lysosomes sequester Ca2+ released by all IP3 R subtypes, but not Ca2+ entering cells through store-operated Ca2+ entry (SOCE). A low-affinity Ca2+ sensor targeted to lysosomal membranes reports large, local increases in cytosolic [Ca2+ ] during IP3 -evoked Ca2+ release, but not during SOCE...
December 11, 2018: Cell Reports
https://www.readbyqxmd.com/read/30510138/the-flip-side-of-the-arabidopsis-type-i-proton-pumping-pyrophosphatase-avp1-using-a-trans-membrane-h-gradient-to-synthesize-pyrophosphate
#2
Joachim Scholz-Starke, Cecilia Primo Planta, Jian Yang, Raju Kandel, Roberto A Gaxiola, Kendal D Hirschi
Energy partitioning and plant growth are mediated in part by a type I H+ -pumping pyrophosphatase (H+ -PPase). A canonical role for this transporter has been demonstrated at the tonoplast where it serves a job-sharing role with V-ATPase in vacuolar acidification. Here, we investigated whether the plant H+ -PPase from Arabidopsis also functions in "reverse mode", to synthesize PPi using the trans-membrane H+ gradient. Using patch-clamp recordings on Arabidopsis vacuoles, we observed inward currents upon Pi application on the cytosolic side...
December 3, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30500180/human-cytosolic-and-mitochondrial-serine-hydroxymethyltransferase-isoforms-in-comparison-full-kinetic-characterization-and-substrate-inhibition-properties
#3
Angela Tramonti, Caterina Nardella, Martino Luigi di Salvo, Anna Barile, Francesca Cutruzzolà, Roberto Contestabile
Serine hydroxymethyltransferase (SHMT) catalyses the reversible conversion of L-serine and tetrahydrofolate into glycine and 5,10-methylenetetrahydrofolate. This enzyme, which plays a pivotal role in one-carbon metabolism, is involved in cancer metabolic reprogramming and is a recognised target of chemotherapy intervention. In humans, two isoforms of the enzyme exist, which are commonly referred to as cytosolic SHMT1 and mitochondrial SHMT2. Considerable attention has been directed on the structural, mechanistic and metabolic features of these isozymes...
November 30, 2018: Biochemistry
https://www.readbyqxmd.com/read/30476561/cellular-stress-is-a-prerequisite-for-glucose-induced-mitochondrial-matrix-alkalinization-in-pancreatic-%C3%AE-cells
#4
Isabelle Chareyron, Christopher Wall, Jonathan Thevenet, Jaime Santo-Domingo, Andreas Wiederkehr
Changes in mitochondrial and cytosolic pH alter the chemical gradient across the inner mitochondrial membrane. The proton chemical gradient contributes to mitochondrial ATP synthesis as well as the uptake and release of metabolites and ions from the organelle. Here mitochondrial pH and ΔpH were studied for the first time in human pancreatic β-cells. Adenoviruses were used for rat insulin promoter dependent expression of the pH sensor SypHer targeted to either the mitochondrial matrix or the cytosol. The matrix pH in resting human β-cells is low (pH = 7...
November 23, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/30468943/photocytotoxic-copper-ii-complexes-of-n-salicylyl-l-tryptophan-and-phenanthroline-bases
#5
Atrayee Banaspati, Dhananjay Das, Chandan J Choudhury, Arnab Bhattacharyya, Tridib K Goswami
Four ternary copper(II) complexes of N-salicylyl-l-Tryptophan (Sal-TrpH) and phenanthroline bases of general formula [Cu(Sal-Trp)(L)], where L is 1,10-phenanthroline (phen, 1), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq, 2), dipyrido[3,2-a:2',3'-c]phenazine (dppz, 3) and 2-(anthracen-1-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (aip, 4), were synthesized and fully characterized. The complexes were evaluated for their affinity for biomolecules and photocytotoxic activities. Single crystal X-ray diffraction studies of complex 1 revealed that it has a square pyramidal CuN3 O2 core with the phenolate oxygen of salicylaldehyde occupying the axial coordination site in the solid state...
November 9, 2018: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/30457515/srca-is-a-chaperone-for-the-salmonella-spi-2-type-three-secretion-system-effector-sted
#6
Camilla Godlee, Ondrej Cerny, Charlotte H Durkin, David W Holden
Effector proteins of type three secretion systems (T3SS) often require cytosolic chaperones for their stabilization, to interact with the secretion machinery and to enable effector delivery into host cells. We found that deletion of srcA, previously shown to encode a chaperone for the Salmonella pathogenicity island 2 (SPI-2) T3SS effectors SseL and PipB2, prevented the reduction of mature Major Histocompatibility Complex class II (mMHCII) from the surface of antigen-presenting cells during Salmonella infection...
November 20, 2018: Microbiology
https://www.readbyqxmd.com/read/30452451/selective-inhibition-of-carbonic-anhydrase-ix-over-carbonic-anhydrase-xii-in-breast-cancer-cells-using-benzene-sulfonamides-disconnect-between-activity-and-growth-inhibition
#7
Mam Y Mboge, Zhijuan Chen, Alyssa Wolff, John V Mathias, Chingkuang Tu, Kevin D Brown, Murat Bozdag, Fabrizio Carta, Claudiu T Supuran, Robert McKenna, Susan C Frost
Carbonic anhydrases (CAs) have been linked to tumor progression, particularly membrane-bound CA isoform IX (CA IX). The role of CA IX in the context of breast cancer is to regulate the pH of the tumor microenvironment. In contrast to CA IX, expression of CA XII, specifically in breast cancer, is associated with better outcome despite performing the same catalytic function. In this study, we have structurally modeled the orientation of bound ureido-substituted benzene sulfonamides (USBs) within the active site of CA XII, in comparison to CA IX and cytosolic off-target CA II, to understand isoform specific inhibition...
2018: PloS One
https://www.readbyqxmd.com/read/30447687/a-sglt2-inhibitor-dapagliflozin-suppresses-prolonged-ventricular-repolarization-through-augmentation-of-mitochondrial-function-in-insulin-resistant-metabolic-syndrome-rats
#8
Aysegul Durak, Yusuf Olgar, Sinan Degirmenci, Erman Akkus, Erkan Tuncay, Belma Turan
BACKGROUND: Metabolic syndrome (MetS) is a prevalent risk factor for cardiac dysfunction. Although SGLT2-inhibitors have important cardioprotective effects in hyperglycemia, their underlying mechanisms are complex and not completely understood. Therefore, we examined mechanisms of a SGLT2-inhibitor dapagliflozin (DAPA)-related cardioprotection in overweight insulin-resistant MetS-rats comparison with insulin (INSU), behind its glucose-lowering effect. METHODS: A 28-week high-carbohydrate diet-induced MetS-rats received DAPA (5 mg/kg), INSU (0...
November 17, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/30411322/metabolic-flux-balance-analysis-during-lactate-and-glucose-concomitant-consumption-in-hek293-cell-cultures
#9
I Martínez-Monge, J Albiol, M Lecina, L Liste-Calleja, J Miret, C Solà, J J Cairó
At early stages of the exponential growth phase in HEK293 cell cultures, tricarboxylic acid cycle is unable to process all the amount of NADH generated in the glycolysis pathway, being lactate the main by-product. However, HEK293 cells are also able to metabolize lactate depending on the environmental conditions. It has recently been observed that one of the most important modes of lactate metabolization is the co-metabolism of lactate and glucose, observed even during the exponential growth phase. Extracellular lactate concentration and pH appear to be the key factors triggering the metabolic shift from glucose consumption and lactate production to lactate and glucose concomitant consumption...
November 8, 2018: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/30404903/potassium-fertilization-arrests-malate-accumulation-and-alters-soluble-sugar-metabolism-in-apple-fruit
#10
Wen Zhang, Xian Zhang, Yufei Wang, Nishang Zhang, Yanping Guo, Xiaolin Ren, Zhengyang Zhao
Effects of different potassium (K) levels, which were K0 (no fertilizer), K1 (71.5g KCl Plant-1 yr-1 ), K2 (286.7g KCl Plant-1 yr-1 ), and K3 (434g KCl Plant-1 yr-1 ), were evaluated based on sugar and organic acid metabolism levels from 70 to 126 days after bloom (DAB) in the developing fruit of potted five-year old apple ( Malus domestica, Borkh.) trees. The results indicate that K fertilization promoted greater fruit mass, higher Ca2+ and soluble solid content, and lower titratable acid content, as well as increased pH values at harvest...
November 7, 2018: Biology Open
https://www.readbyqxmd.com/read/30403147/metabolism-and-redox-in-pulmonary-vascular-physiology-and-pathophysiology
#11
Norah Alruwaili, Sharath Kandhi, Dong Sun, Michael S Wolin
This review considers how some systems controlling pulmonary vascular function are potentially regulated by redox processes to examine how and why conditions such as prolonged hypoxia, pathological mediators and other factors promoting vascular remodeling contribute to the development of pulmonary hypertension (PH). Aspects of vascular remodeling induction mechanisms are described associated with shifts in glucose metabolism through the pentose phosphate pathway and increased cytosolic NADPH generation by glucose-6-phosphate dehydrogenase, increased glycolysis generation of cytosolic NADH and lactate, mitochondrial dysfunction associated with superoxide dismutase-2 depletion, changes in reactive oxygen species and iron metabolism, and redox signaling...
November 7, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/30391286/cytotoxic-action-of-acetate-on-tumor-cells-of-thymic-origin-role-of-mct-1-ph-homeostasis-and-altered-cell-survival-regulation
#12
Shrish Kumar Pandey, Saveg Yadav, Yugal Goel, Sukh Mahendra Singh
Neoplastic cells display altered biosynthetic and bioenergetic machinery to support cell survival. Therefore, cancer cells optimally utilize all available fuel resources to pump their highly upregulated metabolic pathways. While glucose is the main carbon source, transformed cells also utilize other molecules, which can be utilized in metabolic pathways, designated as alternative fuels. Acetate is one of such alternative metabolic fuels, which is mainly consumed in carbohydrate and lipid metabolism. However, studies demonstrate the contradictory effects of acetate on tumor cell survival...
November 1, 2018: Biochimie
https://www.readbyqxmd.com/read/30386244/intracellular-delivery-of-rapamycin-from-fkbp-elastin-like-polypeptides-is-consistent-with-macropinocytosis
#13
Santosh Peddi, Xiaoli Pan, John Andrew MacKay
Rapamycin (Rapa) is a highly potent drug; however, its clinical potential is limited by poor solubility, bioavailability, and cytotoxicity. To improve Rapa delivery, our team has fused the cognate protein receptor for Rapa, FKBP12, to high molecular weight elastin-like polypeptides (ELPs). One construct, FAF, includes an FKBP domain at each termini of an ELP. In a recent report, FAF/Rapa outperformed a family of related carriers with higher tumor accumulation and efficacy. Despite apparent efficacy, an explanation for how FAF carries Rapa into cells has not been elucidated...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/30360105/cascade-cytosol-delivery-of-dual-sensitive-micelle-tailored-vaccine-for-enhancing-cancer-immunotherapy
#14
Dandan Jiang, Weiwei Mu, Xiuping Pang, Yongjun Liu, Na Zhang, Yunmei Song, Sanjay Garg
Enhancing cytosol delivery of exogenous antigens in antigen presenting cells can improve cross-presentation and CD8+ T cell-mediated immune response. The antigen cytosol delivery speed, which has great importance on the rate of MHC class I molecules (MHC I) antigen presentation pathway and cytotoxic T lymphocytes (CTLs) induction, has not been well studied. We hypothesized that micelle-tailored vaccine with multiple cascaded lysosomal responsive capabilities could accelerate lysosomal escape and enhance cancer immunotherapy...
October 15, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/30358990/in-situ-photoregulation-of-carbonic-anhydrase-activity-using-azobenzenesulfonamides
#15
Kanchan Aggarwal, Mandira Banik, Brenda Medellin, Emily L Que
We report two small molecule azobenzenesulfonamide probes, CAP1 and CAP2, capable of photomodulating the activity of carbonic anhydrase (CA) on demand. In the trans form, CAP azobenzene probes adopt a linear shape, making them suitable for occupying the CA active site and interacting with Zn2+ , thereby inhibiting enzyme activity. Following irradiation with either 365 or 410 nm light, the CAP probes isomerize to their cis form. Because of the change in steric profile, the probe exits the active site, and the activity of the enzyme is restored...
November 1, 2018: Biochemistry
https://www.readbyqxmd.com/read/30358436/divergent-changes-of-p53-in-pulmonary-arterial-endothelial-and-smooth-muscle-cells-involved-in-the-development-of-pulmonary-hypertension
#16
Ziyi Wang, Kai Yang, Qiuyu Zheng, Chenting Zhang, Haiyang Tang, Aleksandra Babicheva, Qian Jiang, Meichan Li, Yuqin Chen, Shane G Carr, Kang Wu, Qian Zhang, Angela Balistrieri, Christina Wang, Shanshan Song, Ramon J Ayon, Ankit A Desai, Stephen M Black, Joe G N Garcia, Ayako Makino, Jason X-J Yuan, Wenju Lu, Jian Wang
The tumor-suppressive role of p53, a transcription factor that regulates the expression of many genes, has been linked to cell cycle arrest, apoptosis, andsenescence. The non-canonical function or the pathogenic role of p53 has more recently been implicatedin pulmonary vascular disease.We previously reported that rapid nuclear accumulation of hypoxia-inducible factor (HIF)-1α in pulmonary arterial smooth muscle cells (PASMCs) upregulates TRPC channels and enhances Ca2+ entry to increase cytosolic Ca2+ concentration ([Ca2+ ]cyt )...
October 25, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/30351034/magnesium-stable-isotope-fractionation-on-a-cellular-level-explored-by-cyanobacteria-and-black-fungi-with-implications-for-higher-plants
#17
Rasesh Pokharel, Ruben Gerrits, Jan A Schuessler, Patrick J Frings, Roman Sobotka, Anna A Gorbushina, Friedhelm von Blanckenburg
In a controlled growth experiment we found that the cyanobacterium Nostoc punctiforme has a bulk cell 26 Mg/24 Mg ratio (expressed as δ26 Mg) that is -0.27‰ lower than the growth solution at a pH of ca. 5.9. This contrasts with a recently published δ26 Mg value that was 0.65‰ higher than growth solution for the black fungus Knufia petricola at similar laboratory conditions, interpreted to reflect loss of 24 Mg during cell growth. By a mass balance model constrained by δ26 Mg in chlorophyll extract we inferred the δ26 Mg value of the main Mg compartments in a cyanobacteria cell: free cytosolic Mg (-2...
October 26, 2018: Environmental Science & Technology
https://www.readbyqxmd.com/read/30347449/the-fluorescent-protein-sensor-rogfp2-orp1-monitors-in-vivo-h-2-o-2-and-thiol-redox-integration-and-elucidates-intracellular-h-2-o-2-dynamics-during-elicitor-induced-oxidative-burst-in-arabidopsis
#18
Thomas Nietzel, Marlene Elsässer, Cristina Ruberti, Janina Steinbeck, José Manuel Ugalde, Philippe Fuchs, Stephan Wagner, Lara Ostermann, Anna Moseler, Philipp Lemke, Mark D Fricker, Stefanie J Müller-Schüssele, Bruno M Moerschbacher, Alex Costa, Andreas J Meyer, Markus Schwarzländer
Hydrogen peroxide (H2 O2 ) is ubiquitous in cells and at the centre of developmental programmes and environmental responses. Its chemistry in cells makes H2 O2 notoriously hard to detect dynamically, specifically and at high resolution. Genetically encoded sensors overcome persistent shortcomings, but pH sensitivity, silencing of expression and a limited concept of sensor behaviour in vivo have hampered any meaningful H2 O2 sensing in living plants. We established H2 O2 monitoring in the cytosol and the mitochondria of Arabidopsis with the fusion protein roGFP2-Orp1 using confocal microscopy and multiwell fluorimetry...
October 22, 2018: New Phytologist
https://www.readbyqxmd.com/read/30346842/a-w-o-emulsion-mediated-film-dispersion-method-for-curcumin-encapsulated-ph-sensitive-liposomes-in-the-colon-tumor-treatment
#19
Yi Chen, Qianming Du, Qianqian Guo, Jing Huang, Lina Liu, Xiangchun Shen, Jianqing Peng
The CaCO3 encapsulated liposome with pH sensitivity is an efficient carrier for the delivery of chemotherapeutic drugs. Herein, we provided an innovative method that take advantage of a W/O emulsion to prepare CaCO3 encapsulated liposomes for the delivery of curcumin. The liposomes with both CaCO3 and curcumin encapsulated (LCC) showed highly sensitivity to reduced pH (the environment of lysosomes). Due to the inherent pH sensitivity of CaCO3 , LCC swelled and released the encapsulated curcumin rapidly in acidic medium...
October 22, 2018: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/30338689/probing-translocation-in-mutants-of-the-anthrax-channel-atomically-detailed-simulations-with-milestoning
#20
Piao Ma, Alfredo E Cardenas, Mangesh I Chaudhari, Ron Elber, Susan B Rempe
Anthrax toxin consists of a cation channel and two protein factors. Translocation of the anthrax protein factors from endosomal to the cytosolic compartment is a complex process which utilizes the cation channel. An atomically detailed understanding of the function of the anthrax translocation machinery is incomplete. We report atomically detailed simulations of the lethal factor and channel mutants. Kinetic and thermodynamic properties of early events in the translocation process are computed within the Milestoning theory and algorithm...
November 5, 2018: Journal of Physical Chemistry. B
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