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  • C-peptide increases Na,K-ATPase expression via PKC- and MAP kinase-dependent activation of transcription factor ZEB in human renal tubular cells [Elektronski vir]
    Galuska, Dana ...
    Background: Replacement of proinsulin C-peptide in type 1 diabetes amelioratesnerve and kidney dysfunction, conditions which are associated with a decrease in Na,K-ATPase activity. We determined the ... molecular mechanism by which long term exposure to C-peptide stimulates Na,K-ATPase expression and activity in primary human renal tubular cells (HRTC) in control and hyperglycemic conditions. Methodology/pricipal findings: HRTC were cultured from the outer cortex obtained from patients undergoing elective nephrectomy. Ouabain-sensitive rubidium ((86)Rb(+)) uptake and Na,K-ATPase activity were determined. Abundance of Na,K-ATPase was determined by Western blotting in intact cells or isolated basolateral membranes (BLM). DNA binding activity wasdetermined by electrical mobility shift assay (EMSA). Culturing of HRTCs for 5 days with 1 nM, but not 10 nM of human C-peptide leads to increase in Na,K-ATPase alpha(1)-subunit protein expression, accompanied with increase in (86)Rb(+) uptake, both in normal- and hyperglycemic conditions. Na,K-ATPase alpha(1)-subunit expression and Na,K-ATPase activity were reduced in BLM isolated from cells cultured in presence of high glucose. Exposure to1 nM, butnot 10 nM of C-peptide increased PKCepsilon phosphorylation as well as phosphorylation and abundance of nuclear ERK1/2 regardless of glucose concentration. Exposure to 1 nM of C-peptide increased DNA binding activity of transcription factor ZEB (AREB6), concomitant with Na,K-ATPase alpha(1)-subunit mRNA expression. Effects of 1 nM C-peptide on Na,K-ATPase alpha(1)-subunit expression and/or ZEB DNA binding activity in HRTC were abolished by incubation with PKC or MEK1/2 inhibitors and ZEB siRNA silencing.Conclusions/significance: Despite activation of ERK1/2 and PKC by hyperglycemia, a distinct pool of PKCs and ERK1/2 is involved in regulation ofNa,K-ATPase expression and activity by C-peptide. (Abs. trunc. at 2000 ch.)
    Vir: PloS one [Elektronski vir]. - ISSN 1932-6203 (Vol. 6, issue 12, 2011, str. [1-8] e28294)
    Vrsta gradiva - e-članek
    Leto - 2011
    Jezik - angleški
    COBISS.SI-ID - 29450201

    Povezava(-e):

    http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0028294
    DOI

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