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

by Islam Khan 1,* and Khalid Khan 2
1
Department of Biochemistry, Faculty of Medicine, Kuwait University, Jabriya 24923, Kuwait
2
Department of Anatomy, Faculty of Medicine, Kuwait University, Jabriya 24923, Kuwait
*
Author to whom correspondence should be addressed.
Biomolecules 2019, 9(11), 700; https://doi.org/10.3390/biom9110700
Received: 20 October 2019 / Revised: 2 November 2019 / Accepted: 4 November 2019 / Published: 5 November 2019
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. View Full-Text
Keywords: carbonic anhydrase; Na–H exchanger-1; myeloperoxidase; IBD; colitis carbonic anhydrase; Na–H exchanger-1; myeloperoxidase; IBD; colitis
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Khan, I.; Khan, K. Uncoupling of Carbonic Anhydrase from Na-H exchanger-1 in Experimental Colitis: A Possible Mechanistic Link with Na-H Exchanger. Biomolecules 2019, 9, 700.

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