Volume 19 Supplement 1
Is acute kidney injury in the early phase of sepsis a sign of metabolic downregulation in tubular epithelial cells?
© Jin et al.; licensee BioMed Central Ltd. 2015
Published: 16 March 2015
This study tested the hypothesis that the cellular response in the kidney to sepsis is characterized by early activation of AMP activated protein kinase (AMPK), and that such activation is temporally associated with downregulation of the epithelial sodium channel (B-ENaC).
Fifteen C57BL/6 wildtype (WT) mice were subjected to cecal ligation and puncture (CLP), and sacrificed at 2, 6, 18, 24, or 48 hours. In addition, we pretreated three WT and three AMPK Beta 1 knockout mice with the AMPK activator AICAR (100 mg/kg intraperitoneal, 24 hours before CLP), and sacrificed 24 hours after CLP. Blood and tissue samples were collected for all animals. AMPK activation (pThr172), B-ENaC, and mitophagy (LC3 II/I) were examined by western blot of kidney lysates. Plasma creatinine (Scr) was assessed using ELISA.
AMPK was activated early after induction of sepsis, and was associated with a consistent decrease in Beta-ENaC expression in the apical membrane of tubular epithelial cells. In addition, absence of AMPK activation in KO animals was associated with increased expression of Beta-ENaC at 24 hours after CLP. These data support the hypothesis that early activation of AMPK decreases energy consumption through ion channel downregulation.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.