scholarly journals Carbonic anhydrases enhance activity of endogenous Na‐H exchangers and not the electrogenic Na/HCO 3 cotransporter NBCe1‐A, expressed in Xenopus oocytes

2020 ◽  
Vol 598 (24) ◽  
pp. 5821-5856 ◽  
Author(s):  
Fraser J. Moss ◽  
Walter F. Boron

2013 ◽  
Vol 289 (5) ◽  
pp. 2765-2775 ◽  
Author(s):  
Michael Klier ◽  
Fabian T. Andes ◽  
Joachim W. Deitmer ◽  
Holger M. Becker


2015 ◽  
Author(s):  
Cun Wang ◽  
Honghong Hu ◽  
Xue Qin ◽  
Brian Zeise ◽  
Danyun Xu ◽  
...  

Daily dark periods cause an increase in the leaf CO2 concentration (Ci) and the continuing atmospheric [CO2] rise also increases Ci. Elevated Ci causes closing of stomatal pores thus regulating gas exchange of plants. The molecular signaling mechanisms leading to CO2-induced stomatal closure are only partially understood. Here we demonstrate that high intracellular CO2/HCO3- enhances currents mediated by the guard cell S-type anion channel SLAC1 when co-expressing either of the protein kinases OST1, CPK6 or CPK23 in Xenopus oocytes. Split-ubiquitin screening identified the PIP2;1 aquaporin as an interactor of the βCA4 carbonic anhydrase, which was confirmed in split luciferase, bimolecular fluorescence complementation and co-immunoprecipitation experiments. PIP2;1 exhibited CO2 permeability. Co-expression of βCA4 and PIP2;1 with OST1-SLAC1 or CPK6/23-SLAC1 enabled extracellular CO2 enhancement of SLAC1 anion channel activity. An inactive PIP2;1 point mutation was identified which abrogated water and CO2 permeability and extracellular CO2 regulation of SLAC1 activity in Xenopus oocytes. These findings identify the CO2-permeable PIP2;1 aquaporin as key interactor of carbonic anhydrases, show functional reconstitution of extracellular CO2 signaling to ion channel regulation and implicate SLAC1 as a bicarbonate-responsive protein in CO2 regulation of S-type anion channels.



2019 ◽  
Vol 2 (4) ◽  
pp. 83-98 ◽  
Author(s):  
André De Lima Mota ◽  
Bruna Vitorasso Jardim-Perassi ◽  
Tialfi Bergamin De Castro ◽  
Jucimara Colombo ◽  
Nathália Martins Sonehara ◽  
...  

Breast cancer is the most common cancer among women and has a high mortality rate. Adverse conditions in the tumor microenvironment, such as hypoxia and acidosis, may exert selective pressure on the tumor, selecting subpopulations of tumor cells with advantages for survival in this environment. In this context, therapeutic agents that can modify these conditions, and consequently the intratumoral heterogeneity need to be explored. Melatonin, in addition to its physiological effects, exhibits important anti-tumor actions which may associate with modification of hypoxia and Warburg effect. In this study, we have evaluated the action of melatonin on tumor growth and tumor metabolism by different markers of hypoxia and glucose metabolism (HIF-1α, glucose transporters GLUT1 and GLUT3 and carbonic anhydrases CA-IX and CA-XII) in triple negative breast cancer model. In an in vitro study, gene and protein expressions of these markers were evaluated by quantitative real-time PCR and immunocytochemistry, respectively. The effects of melatonin were also tested in a MDA-MB-231 xenograft animal model. Results showed that melatonin treatment reduced the viability of MDA-MB-231 cells and tumor growth in Balb/c nude mice (p <0.05). The treatment significantly decreased HIF-1α gene and protein expression concomitantly with the expression of GLUT1, GLUT3, CA-IX and CA-XII (p <0.05). These results strongly suggest that melatonin down-regulates HIF-1α expression and regulates glucose metabolism in breast tumor cells, therefore, controlling hypoxia and tumor progression. 



Analgesia ◽  
1995 ◽  
Vol 1 (4) ◽  
pp. 797-800
Author(s):  
Hiroshi Ueda ◽  
Takeaki Miyamae ◽  
Chifumi Hayashi ◽  
Shigeru Watanabe ◽  
Nobuyuki Fukushima ◽  
...  


2019 ◽  
Vol 25 (39) ◽  
pp. 5266-5278 ◽  
Author(s):  
Katia D'Ambrosio ◽  
Claudiu T. Supuran ◽  
Giuseppina De Simone

Protozoans belonging to Plasmodium, Leishmania and Trypanosoma genera provoke widespread parasitic diseases with few treatment options and many of the clinically used drugs experiencing an extensive drug resistance phenomenon. In the last several years, the metalloenzyme Carbonic Anhydrase (CA, EC 4.2.1.1) was cloned and characterized in the genome of these protozoa, with the aim to search for a new drug target for fighting malaria, leishmaniasis and Chagas disease. P. falciparum encodes for a CA (PfCA) belonging to a novel genetic family, the η-CA class, L. donovani chagasi for a β-CA (LdcCA), whereas T. cruzi genome contains an α-CA (TcCA). These three enzymes were characterized in detail and a number of in vitro potent and selective inhibitors belonging to the sulfonamide, thiol, dithiocarbamate and hydroxamate classes were discovered. Some of these inhibitors were also effective in cell cultures and animal models of protozoan infections, making them of considerable interest for the development of new antiprotozoan drugs with a novel mechanism of action.



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