Interference between insulin and estradiol signaling pathways in the regulation of cardiac eNOS and Na(+)/K(+)-ATPase.
Summary of "Interference between insulin and estradiol signaling pathways in the regulation of cardiac eNOS and Na(+)/K(+)-ATPase."
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 40min 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 α2 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 α2. 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 α2 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.
Affiliation
Laboratory for Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia.
Journal Details
This article was published in the following journal.
Name: European journal of pharmacology
ISSN: 1879-0712
Pages: 23-30
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21272573
- DOI: http://dx.doi.org/10.1016/j.ejphar.2011.01.016
Medical and Biotech [MESH] Definitions
Estradiol Congeners
Steroidal compounds related to ESTRADIOL, the major mammalian female sex hormone. Estradiol congeners include important estradiol precursors in the biosynthetic pathways, metabolites, derivatives, and synthetic steroids with estrogenic activities.
Casein Kinase Ialpha
A casein kinase I isoenzyme that plays a role in intracellular signaling pathways including the CELL CYCLE, membrane trafficking, and RNA processing. In DROSOPHILA casein kinase Ialpha has been in regulation of Hedghog and Wingless signaling pathways. Multiple isoforms of casein kinase Ialpha exist and are due ALTERNATIVE SPLICING.
Insulin Receptor Substrate Proteins
A structurally-related group of signaling proteins that are phosphorylated by the INSULIN RECEPTOR PROTEIN-TYROSINE KINASE. The proteins share in common an N-terminal PHOSPHOLIPID-binding domain, a phosphotyrosine-binding domain that interacts with the phosphorylated INSULIN RECEPTOR, and a C-terminal TYROSINE-rich domain. Upon tyrosine phosphorylation insulin receptor substrate proteins interact with specific SH2 DOMAIN-containing proteins that are involved in insulin receptor signaling.
Insulin
A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).
Smad Proteins, Inhibitory
A sub-family of smad proteins that inhibit cell signaling by RECEPTOR-REGULATED SMAD PROTEINS. They form autoinhibitory feedback loops in the TGF-BETA signaling pathway and mediate signaling cross-talk with other signaling pathways
PubMed Articles
The study of the regulatory signaling hierarchies of human heart development is limited by a lack of model systems that can reproduce the precise developmental events that occur during human embryogen...
Insulin/IGF signaling drives cell proliferation in part via Yorkie/YAP.
The insulin/IGF signaling (IIS) pathway is a potent inducer of cell proliferation in normal development and in cancer. The mechanism by which this occurs, however, is not completely understood. The Hi...
Effects of Estradiol and IGF-1 on the Sodium Calcium Exchanger in Rat Cultured Cortical Neurons.
The Na(+)/Ca(2+) exchanger (NCX) is an important bidirectional transporter of calcium in neurons and has been shown to be involved in neuroprotection. Calcium can activate a number of cascades that ca...
Neuroprotective role of estrogens: relationship with insulin/IGF-1 signaling.
Postmenopausal women have an elevated risk of developing a neurodegenerative disease. These clinical observation supported by basic research, suggest that estrogens are neuroprotective. Insulin resist...
The role of endothelial insulin signaling in the regulation of glucose metabolism.
The skeletal muscle is one of the major target organs of insulin and plays an essential role in insulin-induced glucose uptake. Some evidence indicates that insulin delivery to skeletal muscle interst...
Clinical Trials
Panitumumab (Vectibix®) in Cutaneous Squamous Cell Carcinoma (SCC)
Squamous Cell Carcinoma (SCC) is one of the most common malignancies in caucasian population. The effect of the immune system on the development of skin tumors has been demonstrated in tra...
Prevention of Obesity in Women Via Estradiol Regulation
The purpose of this study is to evaluate potential mechanisms by which estradiol deficiency accelerates fat gain and abdominal fat accumulation in women.
The Potential Interference of Magnets From a Surgical Magnetic Drape With Cardiac Pacemakers
Magnetic fields may interfere with the function of cardiac pacemakers. A magnetic drape to hold surgical instruments is widely used in surgery. The use of this drape on pacemaker patients...
Steroid-induced Reduction of Surgical Stress Study
The stress response as induced by myocardial cellular damage during cardiac surgery may lead to myocardial stunning and apoptosis, and could therefore impair postoperative patient recovery...
Proximal Molecular Effects of Concurrent Chemoradiotherapy on Head and Neck Squamous Cell Carcinoma
This pilot study seeks to evaluate the feasibility of measuring the proximal effects of concurrent chemoradiotherapy (CRT) on the expression of potential therapeutic target molecules in He...
