Skip to Content
Merck
  • Early targets of lithium in rat kidney inner medullary collecting duct include p38 and ERK1/2.

Early targets of lithium in rat kidney inner medullary collecting duct include p38 and ERK1/2.

Kidney international (2014-05-03)
Francesco Trepiccione, Trairak Pisitkun, Jason D Hoffert, Søren B Poulsen, Giovambattista Capasso, Søren Nielsen, Mark A Knepper, Robert A Fenton, Birgitte M Christensen
ABSTRACT

Almost half of patients receiving lithium salts have nephrogenic diabetes insipidus. Chronic lithium exposure induces AQP2 downregulation and changes in the cellular composition of the collecting duct. In order to understand these pathophysiological events, we determined the earliest lithium targets in rat inner medullary collecting duct (IMCD) by examining changes in the IMCD phosphoproteome after acute lithium administration. IMCDs were isolated 9 h after lithium exposure, a time when urinary concentrating impairment was evident. We found 1093 unique phosphopeptides corresponding to 492 phosphoproteins identified and quantified by mass spectrometry. Label-free quantification identified 152 upregulated and 56 downregulated phosphopeptides in response to lithium. Bioinformatic analysis highlighted several signaling proteins including MAP kinases and cell-junction proteins. The majority of the upregulated phosphopeptides contained a proline-directed motif, a known target of MAPK. Four hours after lithium exposure, phosphorylation sites in the activation loops of ERK1/2 and p38 were upregulated. Increased expression of phospho-Ser261-AQP2 (proline-directed motif) was concomitant with the increase in urine output. Pretreatment with MAPK inhibitors reversed the increased Ser261-AQP2 phosphorylation. Thus, in IMCD, ERK1/2 and p38 are early targets of lithium and may play a role in the onset of lithium-induced polyuria.

MATERIALS
Product Number
Brand
Product Description

Trolamine, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Triethanolamine, JIS special grade, ≥98.0%
Sigma-Aldrich
Sucrose, JIS special grade
Supelco
Sucrose, Pharmaceutical Secondary Standard; Certified Reference Material
USP
Sucrose, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Triethanolamine, reagent grade, 98%
Sigma-Aldrich
Triethanolamine, BioUltra, ≥99.5% (GC)
Sigma-Aldrich
Triethanolamine, ≥99.0% (GC)
Sigma-Aldrich
Triethanolamine, puriss. p.a., ≥99% (GC)
Sigma-Aldrich
Sucrose, BioUltra, for molecular biology, ≥99.5% (HPLC)
Millipore
Sucrose, suitable for microbiology, ACS reagent, ≥99.0%
Supelco
Sucrose, analytical standard, for enzymatic assay kit SCA20
Sigma-Aldrich
Sucrose, for molecular biology, ≥99.5% (GC)
Sigma-Aldrich
Sucrose, ≥99.5% (GC), BioXtra
Sigma-Aldrich
Sucrose, Grade I, ≥99% (GC), suitable for plant cell culture
Sigma-Aldrich
Sucrose, meets USP testing specifications
Sigma-Aldrich
Sucrose, ≥99.5% (GC), BioReagent, suitable for cell culture, suitable for insect cell culture
Sigma-Aldrich
Sucrose, ≥99.5% (GC), Grade II, suitable for plant cell culture
Sigma-Aldrich
Sucrose, ACS reagent
Sigma-Aldrich
Sucrose, ≥99.5% (GC)
Sigma-Aldrich
Iodoacetamide, Single use vial of 56 mg
Sigma-Aldrich
Iodoacetamide, BioUltra
Sigma-Aldrich
Sucrose, SAJ first grade
SAFC
Iodoacetamide
Sucrose, European Pharmacopoeia (EP) Reference Standard
Supelco
Triethanolamine, analytical standard
Sigma-Aldrich
Sucrose, puriss., meets analytical specification of Ph. Eur., BP, NF
Sigma-Aldrich
Iodoacetamide, ≥99% (NMR), crystalline
Sigma-Aldrich
Sucrose, ≥99.5% (GC)