H2O2 and Src-dependent transactivation of the EGF receptor mediates the stimulatory effect of leptin on renal ERK and Na+, K+-ATPase
| Autor: | Grażyna Wójcicka, Andrzej Marciniak, Jerzy Bełtowski, Jadwiga Trzeciak |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
MAPK/ERK pathway
Leptin medicine.medical_specialty Physiology Renal cortex Biology Kidney Biochemistry Cellular and Molecular Neuroscience Transactivation Endocrinology Epidermal growth factor Internal medicine medicine Animals Na+/K+-ATPase Rats Wistar Extracellular Signal-Regulated MAP Kinases digestive oral and skin physiology Hydrogen Peroxide Rats ErbB Receptors medicine.anatomical_structure src-Family Kinases Sodium-Potassium-Exchanging ATPase Tyrosine kinase hormones hormone substitutes and hormone antagonists Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Peptides. 27(12) |
| ISSN: | 0196-9781 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect