Young Talent Award


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The importance of alpha 2 Na+, K+- ATPase in neuroinflammation
P.F.Kinoshita, A.M.M. Orellana,J.A. Leite, D.Z. Andreotti, L. de Sá Lima, E.M.Kawamoto & C. Scavone
Molecular Neuropharmacology Laboratory, Department of Pharmacology,ICB-USP.

Na,K-ATPase (NKA) is a membrane protein essential for life because NKA plays a role in membrane gradient maintenance. So far, 4 isoforms of alpha subunit (alpha 1,2,3 and 4) were identified and there expression is different between tissues and cell types which may have different physiological roles. In central nervous system, the isoforms alpha 1, 2 and 3 are expressed. The isoform alpha 1 is expressed in all the cells, alpha 3 is expressed in neurons and alpha 2 in glial cells. Firstly, we try to observe the role of alpha 2 expression in glial cells culture treated with ouabain and lipopolysaccharide (LPS). Ouabain is a cardiotonic glycoside that binds to NKA and in low concentrations has a protective effect. LPS was used as a inflammatory model. We thought that alpha 2 would implicate mostly in the ouabain effect. However, silencing alpha 2 showed to decrease the LPS response by preventing NF-kB and ERK activation. Alpha 2 also had a role in IL-1 beta and TNF- alpha levels. Thus, we decided to explore if alpha 2 could also be important in TNFR1 KO mice. We observed that the activity of isoforms alpha 2 and 3 are higher in TNFR1 KO than in WT mice. Since we can not separate the two isoforms in the NKA activity assay, we decided to see the expression of the two proteins separately and we did not see any difference in the expression. The change in activity is probably due to alpha 2 because we also observed an increase in GFAP expression in TNFR1 KO which in only expressed in astrocytes and it is a sign of increase in astrocytic activity. NF-kB is also increased in TNFR1 KO showing that the inflammation is somehow regulated by the increase in alpha 2 activity.

Sponsors: Fapesp, CNPq and CAPES.

Paula F. Kinoshita, ICB-USP –