Browse
Submit Data
Databases
API
Help

Dataset Information

5 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Visible Light Mediated Bidirectional Control over Carbonic Anhydrase Activity in Cells and in Vivo Using Azobenzenesulfonamides.

ABSTRACT: Two azobenzenesulfonamide molecules with thermally stable cis configurations resulting from fluorination of positions ortho to the azo group are reported that can differentially regulate the activity of carbonic anhydrase in the trans and cis configurations. These fluorinated probes each use two distinct visible wavelengths (520 and 410 or 460 nm) for isomerization with high photoconversion efficiency. Correspondingly, the cis isomer of these systems is highly stable and persistent (as evidenced by structural studies in solid and solution state), permitting regulation of metalloenzyme activity without continuous irradiation. Herein, we use these probes to demonstrate the visible light mediated bidirectional control over the activity of zinc-dependent carbonic anhydrase in solution as an isolated protein, in intact live cells and in vivo in zebrafish during embryo development.

SUBMITTER: Aggarwal K

PROVIDER: S-EPMC8063266 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Selective inhibition of carbonic anhydrase IX over carbonic anhydrase XII in breast cancer cells using benzene sulfonamides: Disconnect between activity and growth inhibition.

Project description: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. This has identified specific residues within the CA active site, which differ between isoforms that are important for inhibitor binding and isoform specificity. The ability of these sulfonamides to block CA IX activity in breast cancer cells is less effective than their ability to block activity of the recombinant protein (by one to two orders of magnitude depending on the inhibitor). The same is true for CA XII activity but now they are two to three orders of magnitude less effective. Thus, there is significantly greater specificity for CA IX activity over CA XII. While the inhibitors block cell growth, without inducing cell death, this again occurs at two orders of magnitude above the Ki values for inhibition of CA IX and CA XII activity in their respective cell types. Surprisingly, the USBs inhibited cell growth even in cells where CA IX and CA XII expression was ablated. Despite the potential for these sulfonamides as chemotherapeutic agents, these data suggest that we reconsider the role of CA activity on growth potentiation.

| S-EPMC6242694 | biostudies-literature

Targeting carbonic anhydrase IX activity and expression.

Project description:Metastatic tumors are often hypoxic exhibiting a decrease in extracellular pH (~6.5) due to a metabolic transition described by the Warburg Effect. This shift in tumor cell metabolism alters the tumor milieu inducing tumor cell proliferation, angiogenesis, cell motility, invasiveness, and often resistance to common anti-cancer treatments; hence hindering treatment of aggressive cancers. As a result, tumors exhibiting this phenotype are directly associated with poor prognosis and decreased survival rates in cancer patients. A key component to this tumor microenvironment is carbonic anhydrase IX (CA IX). Knockdown of CA IX expression or inhibition of its activity has been shown to reduce primary tumor growth, tumor proliferation, and also decrease tumor resistance to conventional anti-cancer therapies. As such several approaches have been taken to target CA IX in tumors via small-molecule, anti-body, and RNAi delivery systems. Here we will review recent developments that have exploited these approaches and provide our thoughts for future directions of CA IX targeting for the treatment of cancer.

| S-EPMC6272707 | biostudies-literature

Light-Mediated Control over TRPC3-Mediated NFAT Signaling.

Project description:Canonical transient receptor potential (TRPC) channels were identified as key players in maladaptive remodeling, with nuclear factor of activated T-cells (NFAT) transcription factors serving as downstream targets of TRPC-triggered Ca2+ entry in these pathological processes. Strikingly, the reconstitution of TRPC-NFAT signaling by heterologous expression yielded controversial results. Specifically, nuclear translocation of NFAT1 was found barely responsive to recombinant TRPC3, presumably based on the requirement of certain spatiotemporal signaling features. Here, we report efficient control of NFAT1 nuclear translocation in human embryonic kidney 293 (HEK293) cells by light, using a new photochromic TRPC benzimidazole activator (OptoBI-1) and a TRPC3 mutant with modified activator sensitivity. NFAT1 nuclear translocation was measured along with an all-optical protocol to record local and global Ca2+ pattern generated during light-mediated activation/deactivation cycling of TRPC3. Our results unveil the ability of wild-type TRPC3 to produce constitutive NFAT nuclear translocation. Moreover, we demonstrate that TRPC3 mutant that lacks basal activity enables spatiotemporally precise control over NFAT1 activity by photopharmacology. Our results suggest tight linkage between TRPC3 activity and NFAT1 nuclear translocation based on global cellular Ca2+ signals.

| S-EPMC7140526 | biostudies-literature

Carbonic anhydrase enzymes regulate mast cell-mediated inflammation.

Project description:Type 2 cytokine responses are necessary for the development of protective immunity to helminth parasites but also cause the inflammation associated with allergies and asthma. Recent studies have found that peripheral hematopoietic progenitor cells contribute to type 2 cytokine-mediated inflammation through their enhanced ability to develop into mast cells. In this study, we show that carbonic anhydrase (Car) enzymes are up-regulated in type 2-associated progenitor cells and demonstrate that Car enzyme inhibition is sufficient to prevent mouse mast cell responses and inflammation after Trichinella spiralis infection or the induction of food allergy-like disease. Further, we used CRISPR/Cas9 technology and illustrate that genetically editing Car1 is sufficient to selectively reduce mast cell development. Finally, we demonstrate that Car enzymes can be targeted to prevent human mast cell development. Collectively, these experiments identify a previously unrecognized role for Car enzymes in regulating mast cell lineage commitment and suggest that Car enzyme inhibitors may possess therapeutic potential that can be used to treat mast cell-mediated inflammation.

| S-EPMC4995079 | biostudies-literature

Coherent poly propagation materials with 3-dimensional photonic control over visible light.

Project description:The purpose of the present research was to identify and examine materials demonstrating a previously undiscovered property of coherent poly propagation (CPP). The materials were amorphous silicates as natural precious opals. CPP enabled three-dimensional photonic control over mono and polychromatic visible light wavelengths. CPP caused coherent diffraction of incident poly and monochromatic light. Apart from the iconic play-of-color of precious opal, CPP specimens demonstrated diffractive photonic demultiplexing and/or upconversion and/or downconversion of incident light with strong photonic coherence such that the shape of the incident light source was propagated over three dimensions over multiple visible frequencies. CPP events manifested as each specimen was rocked under the incident light. Additionally, the specimens demonstrated atypical control over internally reflected and transmitted light. The specimens applied axial rotational symmetry over the incident light. Amorphous materials would be expected to exert no symmetry control. CPP and rotational properties occurred in isolation from exogenous thermal, photonic and electrical influences. Furthermore, several non-destructive analytical instruments were employed, such as: spectrophotometer, polariscope and refractometer. The analytical methods revealed unusual behaviors of these specimens. The application of materials demonstrating three-dimensional photonic control will have far-reaching implications for many industries, including: photonic wavelength demultiplexing, fiber optics, imaging, microscopy, projections, security, cryptography, computers and communications.

| S-EPMC6797174 | biostudies-literature

Characterization of Carbonic Anhydrase In Vivo Using Magnetic Resonance Spectroscopy.

Project description:Carbonic anhydrase is a ubiquitous metalloenzyme that catalyzes the reversible interconversion of CO2/HCO3-. Equilibrium of these species is maintained by the action of carbonic anhydrase. Recent advances in magnetic resonance spectroscopy have allowed, for the first time, in vivo characterization of carbonic anhydrase in the human brain. In this article, we review the theories and techniques of in vivo 13C magnetization (saturation) transfer magnetic resonance spectroscopy as they are applied to measuring the rate of exchange between CO2 and HCO3- catalyzed by carbonic anhydrase. Inhibitors of carbonic anhydrase have a wide range of therapeutic applications. Role of carbonic anhydrases and their inhibitors in many diseases are also reviewed to illustrate future applications of in vivo carbonic anhydrase assessment by magnetic resonance spectroscopy.

| S-EPMC7178054 | biostudies-literature

Reversible photo-control over transmembrane anion transport using visible-light responsive supramolecular carriers.

Project description:Ion transport across lipid bilayer membranes in biology is controlled by membrane proteins, which in turn are regulated in response to chemical-, physical- and photo-stimuli. The design of synthetic supramolecular ion transporters able to be precisely controlled by external signals, in particular bio-compatible wavelengths of visible light, is key for achieving spatio-temporal control over function. Here we report two-colour responsive molecular photo-switches that act as supramolecular transmembrane anion carriers. Reversible switching of the photo-switch within the lipid bilayer membrane is achieved using biocompatible visible wavelengths of light, such that temporal control over transmembrane anion transport is achieved through alternating irradiation with red and blue light.

| S-EPMC7472928 | biostudies-literature

carbonic anhydrase (1 or 2) simple or double mutants-Comparative transcriptome analysis between carbonic anhydrase mutants and wild type Arabidopsis

Project description:cea05-01_carbonic-anhydrase - carbonic anhydrase (1 or 2) simple or double mutants - Identification of genes differentially expressed in leaves of single CA1 and CA2 T-DNA insertional mutants and in the corresponding double mutant vs wild type - CA1 (At3g01500) and CA2 (At5g14740) T-DNA insertional mutant lines, the double (CA1+CA2) mutant and wild type Arabidopsis seeds were sown in soil in a phytotron. Leaves were harvested 40 days later for RNA extraction

2012-03-25 | GSE36625 | GEO

Bidirectional light-emitting diode as a visible light source driven by alternating current.

Project description:Gallium nitride-based light-emitting diodes have revolutionized the lighting market by becoming the most energy-efficient light sources. However, the power grid, in example electricity delivery system, is built based on alternating current, which raises problems for directly driving light emitting diodes that require direct current to operate effectively. In this paper, we demonstrate a proof-of-concept device that addresses this fundamental issue - a gallium nitride-based bidirectional light-emitting diode. Its structure is symmetrical with respect to the active region, which, depending on the positive or negative bias, allows for the injection of either electrons or holes from each side. It is composed of two tunnel junctions that surround the active region. In this work, the optical and electrical properties of bidirectional light emitting diodes are investigated under direct and alternating current conditions. We find that the light is emitted in both directions of the supplied current, contrary to conventional light emitting diodes; hence, bidirectional light-emitting diodes can be considered a semiconductor light source powered directly with alternating current. In addition, we show that bidirectional light-emitting diodes can be stacked vertically to multiply the optical power achieved from a single device.

| S-EPMC10661849 | biostudies-literature

carbonic anhydrase (1 or 2) simple or double mutants-Comparative transcriptome analysis between carbonic anhydrase mutants and wild type Arabidopsis

2012-03-25 | E-GEOD-36625 | biostudies-arrayexpress