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

Autores da FMUP
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
- Tipo:
- Article
- Páginas:
- 174153-174153
- Link para outro recurso:
- www.scopus.com
European Journal of Pharmacology Elsevier
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
Citar a publicação
Ant T,Cosme D,Igreja B,Fraga S,Serra MP,Pires NM,Soares da Silva P. The role of salt-inducible kinases on the modulation of renal and intestinal Na<SUP>+</SUP>,K<SUP>+</SUP>-ATPase activity during short- and long-term high-salt intake. Eur. J. Pharmacol. 2021. 904. p. 174153-174153. IF:5,195. (2).