H2O2 and Src-dependent transactivation of the EGF receptor mediates the stimulatory effect of leptin on renal ERK and Na+, K+-ATPase

We examined the mechanism through which leptin increases Na(+), K(+)-ATPase activity in the rat kidney. Leptin was infused under anaesthesia into the abdominal aorta proximally to the renal arteries and then Na(+), K(+)-ATPase activity was measured in the renal cortex and medulla. Leptin (1mug/kgmin...

Full description

Saved in:
Bibliographic Details
Published in:Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2006-12, Vol.27 (12), p.3234-3244
Main Authors: BEŁTOWSKI, Jerzy, WOJCICKA, Grazyna, TRZECIAK, Jadwiga, MARCINIAK, Andrzej
Format: Article
Language:English
Subjects:
Animals
Arterial hypertension. Arterial hypotension
Biological and medical sciences
Blood and lymphatic vessels
Cardiology. Vascular system
Experimental diseases
Extracellular Signal-Regulated MAP Kinases - metabolism
Fundamental and applied biological sciences. Psychology
Hydrogen Peroxide - metabolism
Kidney - enzymology
Leptin - physiology
Medical sciences
Metabolic diseases
Obesity
Rats
Rats, Wistar
Receptor, Epidermal Growth Factor - metabolism
Sodium-Potassium-Exchanging ATPase - metabolism
src-Family Kinases - physiology
Vertebrates: endocrinology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:We examined the mechanism through which leptin increases Na(+), K(+)-ATPase activity in the rat kidney. Leptin was infused under anaesthesia into the abdominal aorta proximally to the renal arteries and then Na(+), K(+)-ATPase activity was measured in the renal cortex and medulla. Leptin (1mug/kgmin) increased Na(+), K(+)-ATPase activity after 3h of infusion, which was accompanied by the increase in urinary H(2)O(2) excretion and phosphorylation level of extracellular signal regulated kinase (ERK). The effect of leptin on ERK and Na(+), K(+)-ATPase was abolished by catalase, specific inhibitors of epidermal growth factor (EGF) receptor, AG1478 and PD158780, as well as by ERK inhibitor, PD98059, and was mimicked by both exogenous H(2)O(2) and EGF. The effect of leptin was also prevented by the inhibitor of Src tyrosine kinase, PP2. Leptin and H(2)O(2) increased Src phosphorylation at Tyr(418). We conclude that leptin-induced stimulation of renal Na(+), K(+)-ATPase involves H(2)O(2) generation, Src kinase, transactivation of the EGF receptor, and stimulation of ERK.
ISSN:0196-9781
1873-5169
DOI:10.1016/j.peptides.2006.08.010