The role of salt-inducible kinases on the modulation of renal and intestinal Na+,K+-ATPase activity during short- and long-term high-salt intake

Data de publicação: Data Ahead of Print:

Autores da FMUP

  • Sónia Alexandra Teixeira Fraga

    Autor

  • Maria Paula De Valadares Souto Pinto Serrão

    Autor

  • Patrício Manuel Vieira Araújo Soares Da Silva

    Autor

Participantes de fora da FMUP

  • Ant, T
  • Cosme, D
  • Igreja, B
  • Pires, NM

Unidades de investigação

Abstract

Type 1 salt-inducible kinases (SIK1) has been shown to act as a mediator during the cellular adaptation to variations in intracellular sodium in a variety of cell types. Type 2 SIK (SIK2) modulates various biological functions and acts as a signal transmitter in various pathways. To evaluate the role of both SIK isoforms in renal and intestinal Na+,K+-ATPase (NKA) activity, we made use of constitutive sik1(-/-) (SIK1-KO), sik2(-/-) (SIK2-KO), double sik1(-/-)sik2(-/-) (double SIK1*2-KO) knockout and wild-type (WT) mice challenged to a standard (0.3% NaCl) or chronic high-salt (HS, 8% NaCl) diet intake for 48 h or 12 weeks. Long-term HS intake in WT was accompanied by 2-fold increase in jejunal NKA activity and slight (similar to 30% reduction) decreases in NKA in the ileum and cecum; none of these changes was accompanied by changes in the expression of alpha(1)-NKA. The ablation of SIK1 and SIK2 prevented the marked increase in jejunal NKA activity following the long-term HS intake. The ablation of SIK1 and SIK2 in mice on a long-term HS intake impacted differently in the ileum and cecum. The most interesting finding is that in SIK2-KO mice marked reductions in NKA activity were observed in the ileum and cecum when compared to WT mice, both on normal and long-term HS intake. In summary, SIK1 or SIK2 ablation on chronic high-salt intake is accompanied by modulation of NKA along the intestinal tract, which differ from those after an acute high-salt intake, and this may represent an absorptive compensatory mechanism to keep electrolyte homeostasis.

Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.

Dados da publicação

ISSN/ISSNe:
0014-2999, 1879-0712

European Journal of Pharmacology  Elsevier

Tipo:
Article
Páginas:
174153-174153
Link para outro recurso:
www.scopus.com

Citações Recebidas na Scopus: 2

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Keywords

  • Salt-inducible kinase 1 (SIK1); Salt-inducible kinase 2 (SIK2); SIK1 knockout mouse; SIK2 knockout mouse; High-salt intake; Na+/K+-ATPase (NKA) activity; Renal NKA; Intestinal NKA

Financiamento

Proyectos asociados

Inervação simpática e mecanismos adrenérgicos locais na regulação funcional da córnea

Investigador Principal: Patrício Manuel Vieira Araújo Soares da Silva

Estudo Clínico Académico . 2019

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