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Nuclear Factor‐kB Mediates Zinc Deficiency‐Induced Sodium Chloride Cotransporter Upregulation in Mouse Distal Convoluted Tubular Cells
Author(s) -
Naraine Meagan K,
Li Mirandy S,
Williams Jasmine,
Mistry Monisha,
Hoover Robert S,
Williams Clintoria R
Publication year - 2017
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.31.1_supplement.857.31
Subject(s) - downregulation and upregulation , cotransporter , chemistry , western blot , endocrinology , medicine , homeostasis , microbiology and biotechnology , sodium , biology , biochemistry , gene , organic chemistry
Zn 2+ deficiency ( ZnD ), a common disorder in chronic kidney disease, contributes to hypertension. However, the mechanism is unknown. The Sodium Chloride Cotransporter ( NCC ) plays a critical role in blood pressure homeostasis. Recently, our lab found that ZnD leads to hyperactivation of NCC that was reversed with Zn 2+ supplementation, suggesting a novel mechanism by which ZnD contributes to hypertension. Other studies have shown that Nuclear Factor‐kB ( NFkB ) is activated in ZnD. The purpose of this study was to determine the role NFkB plays in ZnD‐induced NCC upregulation. We hypothesize that ZnD activates NFkB, which leads to an upregulation of NCC. To investigate this mechanism, mouse distal convoluted tubular ( mDCT‐15 ) cells were treated with the pharmacological agent Caffeic acid phenethyl ester ( CAPE ), a NFkB inhibitor, for 24 hours prior to inducing ZnD with the Zn 2+ chelator TPEN for an additional 24 hours. NCC expression (via Western blot, qRT‐PCR, and immunofluorescence) and localization (via biotinylation) were examined. Compared to vehicle, TPEN increases NCC mRNA and protein expression. Additionally, NCC surface localization was enhanced. However, NFkB inhibition with CAPE prevents TPEN‐induced NCC upregulation. Based on these results, it is apparent that NFkB plays a role in ZnD‐induced NCC upregulation in mDCT‐15 cells. Understanding the mechanisms by which ZnD contributes to hypertension may have an important impact on the treatment of blood pressure dysregulation. Support or Funding Information Funding: NIH‐T32 (CRW); NIH‐ROI (RSH); VA‐MERIT (RSH); SUPERR (MKN)