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Phosphoproteomic Analysis of Signaling Responses to Angiotensin II in Proximal Tubules of NHE3‐deficient Mice
Author(s) -
Li Xiao C,
MiguelQin Elisa,
Shull Gary E,
Zhuo Jia L
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.1165.19
Subject(s) - sodium–hydrogen antiporter , endocrinology , medicine , angiotensin ii , chemistry , protein kinase c , creb , kidney , renin–angiotensin system , western blot , kinase , biology , sodium , biochemistry , blood pressure , transcription factor , organic chemistry , gene
Mice with the Na + /H + exchanger 3 deficiency ( Nhe3−/− ) develop hypotension, suggesting an important role of NHE3 in the proximal tubule of the kidney. Using control ( Nhe3+/+ ) and Nhe3−/− mice, we determined blood pressure (SBP) and signaling responses to angiotensin II (ANG II) for 2 weeks (40 ng/min, i.p., via osmotic minipump). Na + ‐K + ‐ATPase α1, Na + /HCO 3 − , phosphorylated PKCα (p‐PKCα), glycogen synthase kinase 3α/β (p‐GSK3α/β), MAP kinases ERK1/2 (p‐ERK1/2), CREB (p‐ CREB), and aquaporin 1 (AQP‐1) proteins in the proximal tubule of the kidney were measured by western blot analysis. Under basal conditions, Nhe3−/− mice had lower SBP ( p <0.01) and 24 h urinary water, Na + and K + excretion ( p <0.01). Plasma ANG II and aldosterone were significantly elevated ( p <0.01), but kidney ANG II was unaltered in Nhe3−/− mice. Na + ‐K + ‐ATPase α1, Na + /HCO 3 − , p‐PKCα, p‐GSK3α/β, p‐ERK1/2, and AQP‐1 proteins were significantly increased in Nhe3−/− mice compared with Nhe3+/+ mice ( p <0.01). ANG II increased SBP and 24 h urinary Na + and K + excretion to greater extents in Nhe3+/+ than in Nhe3−/− mice. Although ANG II increased Na + ‐K + ‐ATPase α1, Na + /HCO 3 − , p‐ PKCα, p‐ERK1/2, and AQP‐1 signaling responses in Nhe3+/+ mice, it had no effects on these signaling proteins in Nhe3−/− mice. We concluded that global deletion of the NHE3 gene induces significant compensatory transporter and signaling responses in the proximal tubule of the kidney.