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

• Type: Article in International Scientific Journal
• Date: 2021

Authors

Ant, T (Author) Other; Cosme, D (Author) Other; Igreja, B (Author) Other; Sonia Fraga (Author) FMUP; Maria Paula Serrão (Author) FMUP; Pires, NM (Author) Other; soares-da-silva, p (Author) FMUP

Journal

Title: European Journal of Pharmacology

Vol. 904

ISSN: 0014-2999

Publisher: Elsevier

Indexing

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Other information

Authenticus ID: P-00T-WW1

DOI: 10.1016/j.ejphar.2021.174153

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9