| Texto completo | |
| Autor(es): |
Leite, J. A.
;
Isaksen, T. J.
;
Heuck, A.
;
Scavone, C.
;
Lykke-Hartmann, K.
Número total de Autores: 5
|
| Tipo de documento: | Artigo Científico |
| Fonte: | SCIENTIFIC REPORTS; v. 10, n. 1, p. 21-pg., 2020-08-25. |
| Resumo | |
Na+/K+-ATPase is a transmembrane ion pump that is essential for the maintenance of ion gradients and regulation of multiple cellular functions. Na+/K+-ATPase has been associated with nuclear factor kappa B (NF kappa B) signalling, a signal associated with lipopolysaccharides (LPSs)-induced immune response in connection with activated Toll-like receptor 4 (TLR4) signalling. However, the contribution of Na+/K+-ATPase to regulating inflammatory responses remains elusive. We report that mice haploinsufficient for the astrocyte-enriched alpha Na-2(+)/K+-ATPase isoform (alpha(+/G301R)(2) mice) have a reduced proinflammatory response to LPS, accompanied by a reduced hypothermic reaction compared to wild type litter mates. Following intraperitoneal injection of LPS, gene expressions of Tnf-alpha, Il-1 beta, and Il-6 was reduced in the hypothalamus and hippocampus from alpha(+/G301R)(2) mice compared to alpha(+/+)(2) littermates. The alpha(+/G301R)(2) mice experienced increased expression of the gene encoding an antioxidant enzyme, NRF2, in hippocampal astrocytes. Our findings indicate that alpha Na-2(+)/K+-ATPase haploinsufficiency negatively modulates LPS-induced immune responses, highlighting a rational pharmacological target for reducing LPS-induced inflammation. (AU) | |
| Processo FAPESP: | 16/07427-8 - Envelhecimento e neuroproteção: ações da proteína Klotho no metabolismo energético, sinalização da Na,K-ATPase e respostas adaptativas no sistema nervoso central |
| Beneficiário: | Cristoforo Scavone |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 14/10171-0 - Avaliação do papel modulador da ouabaína no eixo hipotalâmico-pituitário-adrenal em ratos submetidos ao estresse crônico imprevisível |
| Beneficiário: | Jacqueline Alves Leite |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |
| Processo FAPESP: | 16/21343-1 - Estudo do efeito do LPS no modelo das mutações das isoformas ±2- ou ±3 Na+/K+ -ATPase em camundongos |
| Beneficiário: | Jacqueline Alves Leite |
| Modalidade de apoio: | Bolsas no Exterior - Estágio de Pesquisa - Doutorado |