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Redox regulation of the K ATP channel complex in colonic inflammation
Author(s) -
Kang Minho,
Gade Aravind R,
Akbarali Hamid I
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1093.32
Subject(s) - chemistry , nitration , cysteine , nitric oxide , biochemistry , s nitrosylation , tyrosine , enzyme , organic chemistry
Hydrogen sulfide (H 2 S), like nitric oxide (NO) is an endogenous gaseous mediator. Sulfhydration of cysteine residues and tyrosine nitration are post‐translational modifications that alter cellular function. The objective of this study was to define the interaction of tyrosine nitration and cysteine sulfhydration within the K ATP channel in experimental colitis. A modified biotin switch assay was performed to determine sulfhydration of the K ATP channel subunits in CHO transfected cells and in native mouse colonic tissues. NaHS (a donor of H 2 S) significantly enhanced sulfhydration of SUR2B but not Kir6.1 subunit. Treatment with dithiothreitol reversed both the basal and the NaHS‐induced sulfhydration. The basal sulfhydration of SUR2B was significantly enhanced in the mouse colon following inflammation. SIN‐1 (a donor of peroxinitrite) induced nitration of Kir6.1 subunit but not SUR2B. NaHS reduced the nitration of Kir6.1 by SIN‐1. Two specific mutations within SUR2B, C24S and C1455S, prevented sulfhydration by NaHS and failed to decrease tyrosine nitration. The studies described herein suggest that sulfhydration of SUR2B prevents the nitration of Kir6.1. These data suggest that the increase of H2S production observed in colonic inflammation might be a protective mechanism triggered by the protection of nitration of Kir6.1 by sulfhydration of SUR2B.