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carbonic anhydrase

Claudiu T Supuran
Although the role of carbonic anhydrases (CAs, EC in metabolism is well-established, pharmacological applications of this phenomenon started to be considered only recently. In organisms all over the phylogenetic tree, the seven CA genetic families known to date are involved in biosynthetic processes and pH modulation, which may influence metabolism in multiple ways, with both processes being amenable to pharmacologic intervention. CA inhibitors possess antiobesity action directly by inhibiting lipogenesis, whereas the hypoxic tumor metabolism is highly controlled by the transmembrane isoforms CA IX and XII, which contribute to the acidic extracellular environment of tumors and supply bicarbonate for their high proliferation rates...
March 21, 2018: Metabolites
Zhijuan Chen, Lingbao Ai, Mam Y Mboge, Robert McKenna, Christopher J Frost, Coy D Heldermon, Susan C Frost
Human cell lines are an important resource for research, and are often used as in vitro models of human diseases. In response to the mandate that all cells should be authenticated, we discovered that the MDA-MB-231 cells that were in use in our lab, did not validate based on the alleles of 9 different markers (STR Profile). We had been using this line as a model of triple negative breast cancer (TNBC) that has the ability to form tumors in immuno-compromised mice. Based on marker analysis, these cells most closely resembled the MCF10A line, which are a near diploid and normal mammary epithelial line...
March 21, 2018: Cancer Biology & Therapy
Jennifer D Jeffrey, Kelly D Hannan, Caleb T Hasler, Cory D Suski
Multiple environmental stressors may interact in complex ways to exceed or diminish the impacts of individual stressors. In the present study, the interactive effects of two ecologically-relevant stressors (increased temperature and partial pressure of carbon dioxide, pCO2 ) were assessed for freshwater mussels - a group of organisms that are among the most sensitive and rapidly declining worldwide. The individual and combined effects of elevated temperature (22-34˚C) and pCO2 (~230, 58,000 µatm) on juvenile Lampsilis siliquoidea were quantified over a 5- or 14-day period, where physiological and whole-animal responses were measured...
March 21, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Santanu Mandal, Prabuddha Mukhopadhyay, Chiranjit Ghosh, Mithun Pal, Gourab Dutta Banik, Tanmoy Chatterjee, Shibendu Ghosh, Manik Pradhan
The underlying mechanisms towards the progression of end-stage renal disease (ESRD) in chronic kidney disease (CKD) are poorly understood and it still remains a major clinical stumbling block for early detection of CKD. Most patients with CKD pass through ESRD with the necessity of frequent hemodialysis (HD) treatment. At present, plasma urea and creatinine levels are examined in most of the CKD patients to monitor the patients' health status after dialysis. But it is really impossible to get immediate feedback of the patients' health as the conventional tests are involved with the collection of blood samples, laboratory processing for prolong time and finally analysis of those samples...
March 21, 2018: Journal of Breath Research
Andrea Fabianova, Monika Barathova, Lucia Csaderova, Veronika Simko, Miriam Zatovicova, Martina Labudova, Jaromir Pastorek
Renal cell carcinoma is one of the most frequent cancer diseases with high resistance to radio- and chemotherapy. Mutation of VHL gene is frequent in these tumors leading to simulation of hypoxic conditions. Lymphocytic choriomeningitis virus, belonging to RNA viruses, is a neglected human pathogen and teratogen. We have found that infection of renal cell carcinoma cells by lymphocytic choriomeningitis virus strain MX causes a decrease of carbonic anhydrase IX protein and RNA level. Lower expression of carbonic anhydrase IX on the cell surface provides less target for carbonic anhydrase IX-targeted immunotherapy...
February 27, 2018: Oncotarget
Elizabeth S Silagi, Philip Batista, Irving M Shapiro, Makarand V Risbud
The integrity of the avascular nucleus pulposus (NP) phenotype plays a crucial role in the maintenance of intervertebral disc health. While advances have been made to define the molecular phenotype of healthy NP cells, the functional relevance of several of these markers remains unknown. In this study, we test the hypothesis that expression of Carbonic Anhydrase III (CAIII), a marker of the notochordal NP, is hypoxia-responsive and functions as a potent antioxidant without a significant contribution to pH homeostasis...
March 20, 2018: Scientific Reports
Francielle Tatiana Mathias, Douglas Henrique Fockink, Geonildo Rodrigo Disner, Viviane Prodocimo, João Luiz Coelho Ribas, Luiz Pereira Ramos, Marta Margarete Cestari, Helena Cristina Silva de Assis
Ibuprofen is a pharmaceutical drug widely used by the global population and it has been found in aquatic ecosystems in several countries. This study evaluated the effects of ibuprofen in environmental concentrations (0, 0.1, 1 and 10 μg/L) on the freshwaterspecies Rhamdia quelen exposed for 14 days. In the posterior kidney, ibuprofen increased glutathione-S-transferase activity in all groups exposed. Furthermore, increased glutathione peroxidase activity and the levels of reduced glutathione in the group exposed to 10 μg/L...
March 11, 2018: Environmental Toxicology and Pharmacology
Yizhou Li, Roberto De Luca, Samuele Cazzamalli, Francesca Pretto, Davor Bajic, Jörg Scheuermann, Dario Neri
In nature, specific antibodies can be generated as a result of an adaptive selection and expansion of lymphocytes with suitable protein binding properties. We attempted to mimic antibody-antigen recognition by displaying multiple chemical diversity elements on a defined macrocyclic scaffold. Encoding of the displayed combinations was achieved using distinctive DNA tags, resulting in a library size of 35,393,112. Specific binders could be isolated against a variety of proteins, including carbonic anhydrase IX, horseradish peroxidase, tankyrase 1, human serum albumin, alpha-1 acid glycoprotein, calmodulin, prostate-specific antigen and tumour necrosis factor...
March 19, 2018: Nature Chemistry
Fadi M Awadallah, Silvia Bua, Walaa R Mahmoud, Hossam H Nada, Alessio Nocentini, Claudiu T Supuran
Being the primary sulfonamide among the most efficient zinc binding group (ZBG) to design inhibitors for the metallo-enzymes carbonic anhydrases (CA, EC, herein, we propose an investigation on four physiologically important human (h) CAs (hCA I, II, IV, and IX) with N1 -substituted secondary sulfonamides incorporating thiazolinone or imidazolone-indole tails. The effect of the functionalisation of the sulfonamide group with five different substitution patterns, namely acetyl, pyridine, thiazole, pyrimidine, and carbamimidoyl, was evaluated in relation to the inhibition profile of the corresponding primary sulfonamide analogues...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
Marta Menicatti, Marco Pallecchi, Silvia Bua, Daniela Vullo, Lorenzo Di Cesare Mannelli, Carla Ghelardini, Fabrizio Carta, Claudiu T Supuran, Gianluca Bartolucci
Rheumatoid arthritis (RA) is a chronic inflammatory disease caused by a faulty autoimmune response. Recently, it was reported that some human carbonic anhydrases (CAs) isoforms are overexpressed in inflamed synovium of RA patients. New CA inhibitors (CAIs) incorporating CA-binding moiety and the cyclooxygenase inhibitor tail (nonsteroidal anti-inflammatory drug [NSAID] type) were studied. The aim of this work is the evaluation of the chemical stability of NSAID - CAI hybrids towards spontaneous or enzymatic hydrolysis by LC-MS/MS...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
Srinivas Angapelly, P V Sri Ramya, Rohini Sodhi, Andrea Angeli, Krishnan Rangan, Narayana Nagesh, Claudiu T Supuran, Mohammed Arifuddin
A practical and transition metal-free one-pot domino synthesis of diversified (1,3,4-oxadiazol-2-yl)anilines has been developed employing isatins and hydrazides as the starting materials, in the presence of molecular iodine. The prominent feature of this domino process involves consecutive condensation, hydrolytic ring cleavage, and an intramolecular decarboxylation, in a one-pot process that leads to the oxidative formation of a C-O bond. Fluorescence properties of some of the representative molecules obtained in this way were studied...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
Andrea Angeli, Fatmah A S Alasmary, Sonia Del Prete, Sameh M Osman, Zeid AlOthman, William A Donald, Clemente Capasso, Claudiu T Supuran
The activation of the δ-class carbonic anhydrase (CAs, EC from the diatom Thalassiosira weissflogii (TweCAδ) was investigated using a panel of natural and non-natural amino acids and amines. The most effective activator of TweCAδ was d-Tyr (KA of 51 nM), whereas several other amino acids and amines, such as L-His, L-Trp, d-Trp, dopamine and serotonin were submicromolar activators (KA s from 0.51 to 0.93 µM). The most ineffective activator of TweCAδ was 4-amino-l-Phe (18.9 µM), whereas d-His, l-/d-Phe, l-/d-DOPA, l-Tyr, histamine, some pyridyl-alkylamines, l-adrenaline and aminoethyl-piperazine/morpholine were moderately potent activators (KA s from 1...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
Kanij Rukshana Sumi, Soo Cheol Kim, Jewel Howlader, Won Kyo Lee, Kap Seong Choi, Hoy-Taek Kim, Jong-In Park, Ill-Sup Nou, Kang Hee Kho
In this study, an 1888-bp carbonic anhydrase XII (CA XII) sequence was cloned from the brain of the pufferfish, Takifugu rubripes . The cloned sequence contained a coding region of 1470-bp, which was predicted to translate into a protein of 490 amino acid residues. The predicted protein showed between 68-56% identity with the large yellow croaker ( Larimichthys crocea ), tilapia ( Oreochromis niloticus ), and Asian arowana ( Scleropages formosus ) CA XII proteins. It also exhibited 36% and 53% identity with human CA II and CA XII, respectively...
March 13, 2018: International Journal of Molecular Sciences
Ashok Aspatwar, Susanna Haapanen, Seppo Parkkila
Carbonic anhydrases (CAs) are metalloenzymes that are omnipresent in nature. CAs catalyze the basic reaction of the reversible hydration of CO₂ to HCO₃- and H⁺ in all living organisms. Photosynthetic organisms contain six evolutionarily different classes of CAs, which are namely: α-CAs, β-CAs, γ-CAs, δ-CAs, ζ-CAs, and θ-CAs. Many of the photosynthetic organisms contain multiple isoforms of each CA family. The model alga Chlamydomonas reinhardtii contains 15 CAs belonging to three different CA gene families...
March 13, 2018: Metabolites
Katyayani Tatiparti, Samaresh Sau, Kaustubh A Gawde, Arun K Iyer
Triple negative breast cancer (TNBC) is a difficult to treat disease due to the absence of the three unique receptors estrogen, progesterone and herceptin-2 (HER-2). To improve the current therapy and overcome the resistance of TNBC, there is unmet need to develop an effective targeted therapy. In this regard, one of the logical and economical approaches is to develop a tumor hypoxia-targeting drug formulation platform for selective delivery of payload to the drug-resistant and invasive cell population of TNBC tumors...
March 13, 2018: International Journal of Molecular Sciences
Caoileann H Murphy, Mahalakshmi Shankaran, Tyler A Churchward-Venne, Cameron J Mitchell, Nathan M Kolar, Louise M Burke, John A Hawley, Amira Kassis, Leonidas G Karagounis, Kelvin Li, Chelsea King, Marc Hellerstein, Stuart M Phillips
We determined how the pattern of protein intake and resistance training (RT) influenced longer-term (2-wk) integrated myofibrillar protein synthesis (MyoPS) during energy restriction (ER). MyoPS and proteome kinetics were measured during 2-wk of ER alone and 2-wk of ER plus RT (ER + RT) in overweight/obese older men. Participants were randomized to consume dietary protein in a balanced (BAL: 25% daily protein/meal x 4 meals) or skewed (SKEW: 7:17:72:4% daily protein/meal) pattern (n = 10/group). Participants ingested D2 O during the consecutive 2-wk periods, and skeletal muscle biopsies and serum were obtained at the beginning and conclusion of ER and ER + RT...
March 12, 2018: Journal of Physiology
Hiroki Takagi, Yuji Seta, Shinji Kataoka, Mitsushiro Nakatomi, Takashi Toyono, Tatsuo Kawamoto
The gustatory cells in taste buds have been identified as paraneuronal; they possess characteristics of both neuronal and epithelial cells. Like neurons, they form synapses, store and release transmitters, and are capable of generating an action potential. Like epithelial cells, taste cells have a limited life span and are regularly replaced throughout life. However, little is known about the molecular mechanisms that regulate taste cell genesis and differentiation. In the present study, to begin to understand these mechanisms, we investigated the role of Mash1-positive cells in regulating adult taste bud cell differentiation through the loss of Mash1-positive cells using the Cre-loxP system...
March 10, 2018: Anatomical Science International
Murat Bozdag, Fabrizio Carta, Andrea Angeli, Sameh M Osman, Fatmah A S Alasmary, Zeid AlOthman, Claudiu T Supuran
A series of N'-phenyl-N-hydroxyureas has been prepared by reacting hydroxylamine with aromatic isocyanates. These compounds were investigated as inhibitors of human carbonic anhydrases (hCAs, EC, considering four physiologically relevant isoforms, the cytosolic isoforms hCA I and II, and tumor associated, transmembrane isoforms hCA IX and XII. The new compounds reported here did not inhibit the widespread cytosolic isoforms hCA I and II, but they inhibited the tumor associated isoforms with interesting potencies...
March 1, 2018: Bioorganic Chemistry
K Koruza, B Lafumat, Á Végvári, W Knecht, S Z Fisher
Deuterated proteins and other bio-derived molecules are important for NMR spectroscopy, neutron reflectometry, small angle neutron scattering, and neutron protein crystallography. In the current study we optimized expression media and cell culture conditions to produce high levels of 3 different deuterated human carbonic anhydrases (hCAs). The labeled hCAs were then characterized and tested for deuterium incorporation by mass spectrometry (MS), temperature stability, and propensity to crystallize. The results show that is possible to get very good yields (>10 mg of pure protein per liter of cell culture under deuterated conditions) and that protein solubility is unaffected at the crystallization concentrations tested...
March 7, 2018: Archives of Biochemistry and Biophysics
Yasin Tülüce, Bewar Ali Ahmed, İsmail Koyuncu, Mustafa Durgun
Colorectal cancer (CRC) is the third most common tumor, malignant and has developed one of the main reasons of cancer mortality. According to studies conducted recently; carbonic anhydrase 9 (CAIX) is an especially attractive target for cancer therapy, in part since it is limited way expressed in normal tissues on the other hand in a wide variety of solid neoplasia are overexpressed. The aim of this study was to appreciate the effects of CAIX inhibitor, namely novel synthesized sulfonamide derivative (H-4i) with high affinity for CAIX, in CAIX-positive human colorectal cancer cell (HT-29) and CAIX-negative human normal embryonic kidney cell line (HEK-293)...
March 9, 2018: Journal of Bioenergetics and Biomembranes
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