Renal cortical hexokinase and pentose phosphate pathway activation through the EGFR/Akt signaling pathway in endotoxin-induced acute kidney injury.

Renal cortical hexokinase and pentose phosphate pathway activation through the EGFR/Akt signaling pathway in endotoxin-induced acute kidney injury.
Am J Physiol Renal Physiol. 2014 Jul 2;
Authors: Smith JA, Stallons LJ, Schnellmann RG
Abstract
While disruption of energy production is an important contributor to renal injury, metabolic alterations in sepsis-induced AKI remain understudied. We assessed changes in renal cortical glycolytic metabolism in a mouse model of sepsis-induced AKI. A specific and rapid increase in hexokinase (HK) activity (~2 fold) was observed 3 h after lipopolysaccharide (LPS) exposure and maintained up to 18 h, in association with a decline in renal function as measured by BUN. LPS-induced hexokinase activation occurred independently of hexokinase isoform expression or mitochondrial localization. No other changes in glycolytic enzymes were observed. LPS-mediated hexokinase activation was not sufficient to increase glycolytic flux as indicated by reduced or unchanged pyruvate and lactate levels in the renal cortex. LPS-induced hexokinase activation was associated with increased glucose-6-phosphate dehydrogenase activity but not glycogen production. Mechanistically, LPS-induced HK activation was attenuated by pharmacological inhibitors of EGFR and Akt, indicating that EGFR/PI3K/Akt signaling is responsible. Our findings reveal LPS rapidly increases renal cortical HK activity in an EGFR- and Akt-dependent manner...

Source: Am J Physiol Renal P... - July 2, 2014 Category: Urology & Nephrology Authors: Smith JA, Stallons LJ, Schnellmann RG Tags: Am J Physiol Renal Physiol Source Type: research