Uncoupling of Carbonic Anhydrase from Na-H exchanger-1 in Experimental Colitis: A Possible Mechanistic Link with Na-H Exchanger

Abstract

In this study, we investigated a mechanistic link between Na–H exchanger-1 (NHE-1) and carbonic anhydrase (CA) in experimental colitis induced in the rats by intrarectal administration of trinitrobenzenesulphonic acid (TNBS). Western blot analysis showed CA-I and CA-II as the major isoforms and CA-IV as a minor one in the colon, and they all are expressed as minor isoforms in the ileum. Co-immunoprecipitation and confocal immunofluorescence microscopy showed colocalization of NHE-1 with CA-I and CA-II, but not with CA-IV. TNBS significantly reduced the levels of NHE-1 and CA protein isoforms in the colon, but not in the uninflamed ileum. A similar reduction profile of the expression of CA isozymes was also obtained in ex vivo treatment of normal colon strips with TNF-α. The level of uncoupling as detected by co-immunoprecipitation was significantly more pronounced. A peptide (83 aa) from the NHE-1 C-terminus demonstrated binding of CA-II only, but not of the CA-I or CA-IV isoform. Furthermore, the profile of inflammatory test markers confirmed inflammation in the tissue used. These findings taken together suggest an inflammation-induced uncoupling of CA and NHE-1, which might be a putative mechanism for reducing the activity of NHE-1 in experimental colitis. This uncoupling might lead to an intracellular accumulation of H+, resulting in acidosis and necrosis in the inflamed colon.

Socializing Models During Lactation Alter Colonic Mucosal Gene Expression and Fecal Microbiota of Growing Piglets

“…Carbonic anhydrase 2 ( CA2 ) and carbonic anhydrase 4 ( CA4 ) are involved in nitrogen metabolism and mainly participate in body acid-base balance and ion exchange. The overexpression or underexpression of carbonic anhydrase (CA) can easily disrupt the CA cycle, which induces an increase in the levels of NA + , Cl − , and water in the lumen, leading to diarrhea (Endeward et al, 2003 ; Khan and Khan, 2019 ). In our study, compared with the CON group, CA4 was significantly upregulated, but CA2 was significantly downregulated in the CSC group, which may cause CA cycle disorder and affect the health of piglets.…”

Carbonic Anhydrase IV Selective Inhibitors Counteract the Development of Colitis-Associated Visceral Pain in Rats

“…Goblet cells are mucin-secreting intestinal cells that form the mucus layer that protects the mucosal surface. Of note, an increase in H + has been observed in different inflammatory diseases, such as pulmonary hypertension and rheumatoid arthritis [36,37] where acetazolamide showed protective anti-inflammatory effects by a dual mechanism of macrophage carbonic anhydrase inhibition and systemic metabolic acidosis [38]. Recent findings highlighted inflammation-induced uncoupling of CA and sodium-hydrogen antiporter 1 (NHE-1) in experimental colitis, which might lead to an intracellular accumulation of H +, resulting in acidosis and necrosis in the inflamed colon [37].…”

“…Of note, an increase in H + has been observed in different inflammatory diseases, such as pulmonary hypertension and rheumatoid arthritis [36,37] where acetazolamide showed protective anti-inflammatory effects by a dual mechanism of macrophage carbonic anhydrase inhibition and systemic metabolic acidosis [38]. Recent findings highlighted inflammation-induced uncoupling of CA and sodium-hydrogen antiporter 1 (NHE-1) in experimental colitis, which might lead to an intracellular accumulation of H +, resulting in acidosis and necrosis in the inflamed colon [37]. The colon surface, flattened during active colitis, presents colonic crypt elongation and, eventually, goblet cells hyperplasia during the recovery phase of acute colitis.…”

Syngas from What? Comparative Life-Cycle Assessment for Syngas Production from Biomass, CO2, and Steel Mill Off-Gases

“…Current studies mainly evaluate alternative syngas pathways for power generation. ,, Although a large proportion of syngas is used chemically, only a few studies have been published. These studies do not assess bio-based and CO 2 -based syngas directly but its material use in methanol, dimethyl ether, or Fischer–Tropsch processes. ,− Most of these studies compare the environmental benefits of products from alternative syngas to their fossil benchmark and quantify potential savings in GHG emissions. ,− In addition, some studies compare the environmental benefits of either bio-based or CO 2 -based production pathways. ,, Thus, the latter studies identify the most promising syngas pathways for one alternative feedstock.…”