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

Abstract:

: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.

journal_name

Peptides

journal_title

Peptides

authors

Bełtowski J,Wójcicka G,Trzeciak J,Marciniak A

doi

10.1016/j.peptides.2006.08.010

subject

Has Abstract

pub_date

2006-12-01 00:00:00

pages

3234-44

issue

12

eissn

0196-9781

issn

1873-5169

pii

S0196-9781(06)00379-2

journal_volume

27

pub_type

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