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J. Biol. Chem. 286 (52): 45041-45047

© 2011 by The American Society for Biochemistry and Molecular Biology, Inc.

Background: Albumin interacts with megalin and triggers cellular responses in proximal tubule cells.

Results: Albumin modulates the PI3K/protein kinase B, protein kinase C, and protein kinase A pathways promoting the regulation of the (Na+ + K+)-ATPase expression.

Conclusion: Variation in the albumin concentration in the proximal tubule affects sodium reabsorption.

Significance: These results open new avenues to understanding the role of albumin in proximal tubule cells.

(Na+ + K+)-ATPase Is a Target for Phosphoinositide 3-Kinase/Protein Kinase B and Protein Kinase C Pathways Triggered by Albumin*

Diogo B. Peruchetti{ddagger}, Ana Acacia S. Pinheiro{ddagger}, Sharon S. Landgraf{ddagger}, Mira Wengert{ddagger}, Christina M. Takiya{ddagger}, William B. Guggino§, , and Celso Caruso-Neves{ddagger}1

From the {ddagger}Instituto de Biofísica Carlos Chagas Filho/Universidade Federal Rio de Janeiro, Centro de Ciências da Saúde, Bloco G, 21949-900 Rio de Janeiro, Brazil and
the §Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

ABSTRACT Back to Top

Abstract: In recent decades, evidence has confirmed the crucial role of albumin in the progression of renal disease. However, the possible role of signaling pathways triggered by physiologic concentrations of albumin in the modulation of proximal tubule (PT) sodium reabsorption has not been considered. In the present work, we have shown that a physiologic concentration of albumin increases the expression of the α1 subunit of (Na+ + K+)-ATPase in LLC-PK1 cells leading to an increase in enzyme activity. This process involves the sequential activation of PI3K/protein kinase B and protein kinase C pathways promoting inhibition of protein kinase A. This integrative network is inhibited when albumin concentration is increased, similar to renal disease, leading to a decrease in the α1 subunit of (Na+ + K+)-ATPase expression. Together, the results indicate that variation in albumin concentration in PT cells has an important effect on PT sodium reabsorption and, consequently, on renal sodium excretion.

Key Words: Epithelial Cell • Kidney • Na,K-ATPase • Protein Kinases • Sodium Transport • Albuminuria • Proximal Tubule • Renal Disease • Signaling Pathways • Sodium Pump

Received for publication May 16, 2011. Revision received October 25, 2011.

1 To whom correspondence should be addressed: Avenida Carlos Chagas Filho 373, Cidade Universitária, 21949-900 Rio de Janeiro, Brazil. Tel.: 55-21-2562-6582; Fax: 55-21-2280-8193; E-mail: caruso{at}

2011 Homer Smith Award: To Serve and Protect: Classic and Novel Roles for Na+,K+-Adenosine Triphosphatase.
A. Aperia (2012)
J. Am. Soc. Nephrol. 23, 1283-1290
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