Interference between insulin and estradiol signaling pathways in the regulation of cardiac eNOS and Na+/K+-ATPase

Autor: Zorica Zakula, Tijana Milosavljevic, Esma R. Isenovic, Mojca Stojiljkovic, Goran Koricanac, Snezana Tepavcevic
Rok vydání: 2011
Předmět:
Blood Glucose
medicine.medical_specialty
Nitric Oxide Synthase Type III
medicine.drug_class
medicine.medical_treatment
030204 cardiovascular system & hematology
Biology
Fatty Acids
Nonesterified
03 medical and health sciences
0302 clinical medicine
Protein kinase B
Enos
Internal medicine
medicine
Animals
Insulin
Drug Interactions
Na+/K+-ATPase
Phosphorylation
Rats
Wistar
030304 developmental biology
Pharmacology
Mitogen-Activated Protein Kinase 1
0303 health sciences
Mitogen-Activated Protein Kinase 3
Estradiol
Kinase
Myocardium
Sodium
biology.organism_classification
Receptor
Insulin
Rats
Potassium ATPase
Endocrinology
Receptors
Estrogen
Estrogen
Nitric oxide synthase type III
Female
Sodium-Potassium-Exchanging ATPase
Extracellular signal-regulated MAP kinase
Proto-Oncogene Proteins c-akt
Hormone
Signal Transduction
Zdroj: European Journal of Pharmacology
Popis: Insulin and estradiol share some of signaling pathways and regulate same target molecules exerting mostly beneficial cardiac effects. in order to study their cardiac interaction, ovariectomized female rats were treated with hormones, separately or simultaneously (20,30 or 40 min before analysis), and the phosphorylations of protein kinase B (Akt), extracellular signal-regulated kinases 1 and 2 (ERK 1/2), endothelial nitric oxide synthase (eNOS) were analyzed, as well as the plasma membrane content of alpha 2 subunit of Na+/K+-ATPase. Insulin, particularly, and estradiol stimulate Ser(473) Akt phosphorylation. The combined treatment was stimulatory, but less than insulin alone was. The general increase of Thr(308) Akt phosphorylation by insulin was stronger than at Ser(473) and reduced in the presence of estradiol, which also stimulated this phosphorylation given alone. The estradiol induction of ERK 1/2 phosphorylation was inverted to the decrease by the combined treatment, while insulin had no effect. Only insulin increased the plasma membrane content of alpha 2. Estradiol did increase the phosphorylation of eNOS, whereas the insulin effect was controversial. The effect of the combined treatment on target molecules was generally opposite to single hormone treatment. In summary, both hormones exerted an effect on Akt phosphorylation, but only estradiol stimulated ERK 1/2 phosphorylation. The alpha 2 plasma membrane content was increased only by insulin, while estradiol increased eNOS phosphorylation more consistently. Finally, if these hormones were administered together, it seems that they disturb each other in having a full effect on cardiac Akt, ERK 1/2, and downstream effectors, eNOS and Na+/K+-ATPase. (c) 2011 Elsevier B.V. All rights reserved.
Databáze: OpenAIRE
Externí odkaz: