Biomedical subjects

Constanza Contreras-Jurado

Publications and source records attributed to Constanza Contreras-Jurado.

4 recordsLinked to original sources

PubMed2025

Thyroid Hormones and Co-workers: An Overview.

The hypothalamus secretes the thyroid-releasing hormone (TRH) that induces the pituitary gland to release the thyroid-stimulating hormone (TSH) which stimulates thyroid follicular cells to release the thyroid hormones (THs), thyroxine (T4), and triiodothyronine (T3). The process of synthesizing T3 and T4 hormones involves various enzymatic steps, starting with the iodination of L-tyrosine residues present in the protein thyroglobulin. Thyroid hormones are released into the bloodstream, where they bind to thyroid hormone distributor proteins (THDPs) which transport them in the circulation. The conversion of T4 to T3 (the more biologically active hormone) in target tissues is facilitated by selenoprotein enzymes known as deiodinases. THs can bind to different molecules located on the plasma membrane, such as integrin αvβ3, through which they exercise regulatory non-genomic control. Nevertheless, most of thyroid hormone's actions are mediated intracellularly by binding to thyroid hormone receptors (TRs). Thyroid hormone receptors act as ligand-dependent transcription factors, Thyroid hormone receptors activate thyroid hormone response elements on gene promoters through canonical signaling. Thyroid hormones mediate several critical physiological processes including organ development, cell differentiation, metabolism, and cell growth and maintenance.

Humans↗

PubMed2006

Different relevance of inactivation and F468 residue in the mechanisms of hEag1 channel blockage by astemizole, imipramine and dofetilide.

The relevance of a point mutation at the C-terminal end of the S6 helix (F468) and the introduction of C-type inactivation in the blockage of hEag1 channels by astemizole, imipramine and dofetilide was tested. C-type inactivation decreased block by astemizole and dofetilide but not imipramine, suggesting different binding sites in the channel. F468C mutation increased IC(50) for astemizole and imipramine but in contrast to HERG channels, only slightly for dofetilide. Together with measurements on recovery of blocking, our observations indicate that the mechanism of hEag1 blockage by each of these drugs is different, and suggest relevant structural differences between hEag1 and HERG channels.

Astemizole↗

PubMed2005

Evidence for simultaneous 1Na+:1Mg2+ and ping pong 2Na+:1Mg2+ exchangers in rat thymocyte.

Rat thymocytes showed two Na+/Mg2+ exchangers with high- and low- affinities for external Na+ (Na+o) at physiological internal Mg2+content. The total internal Mg2+ content (Mg2+it) was enhanced by loading with MgCl2 and the ionophore A-23187. Under these conditions, Na+/Mg2+ exchangers were dramatically stimulated by the Mg2+it increase. Na+-induced Mg2+ effluxes were independent of Cl-o or H+. The Na+/Mg2+ exchangers, which we named HANao (high affinity for Na+o) and LANao (low affinity for Na+o), were dissected in Mg2+-loaded thymocytes according to their kinetics and stoichiometries. HANao, which showed an apparent dissociation constant for Na+o (KNa H) = 9.2 +/- 1.6 mmol l(-1) Na+o and a maximal Na+ influx rate (VNa(Na H)max) = 30.5 +/- 6.1 mmol (l cells)(-1) h(-1), was a 1Na+:1Mg2+ simultaneous antiporter insensitive to external magnesium (Mg2+o) whereas that LANao, with KNa L = 65.1 +/- 8.6 mmol l(-1) Na+ and a VNa(Na L)max = 79.5 +/- 14.3 mmol (l cells)(-1) Na+ h(-1), was a 2Na+:1Mg2+ "ping-pong" antiporter which was strongly inhibited by Mg2+o. At physiological concentration of Mg2+o (1 mM), the Na+/Mg2+ exchange through the LANao was inhibited by approximately 50%. Amiloride (10(-4) M) inhibited at similar extent both Na+ and Mg2+ fluxes at high and at low Na+o.

Amiloride↗

PubMed2004

Fluorometric evidence for different stoichiometries for the Na+/Mg2+ exchange in Mg-loaded rat thymocytes.

The regulation of the cytosolic free magnesium concentration ([Mg2+]i) is a fundamental cellular process that requires magnesium extruding mechanisms. Here, we present evidence indicating that rat thymocytes are endowed with different Na/Mg exchange systems. Fluxes of magnesium were measured using the fluorescent magnesium indicator magfura-2. Cells were loaded with magnesium using the calcium ionophore A-23187 to 0.6-8.0 mM [Mg2+]i (resting [Mg2+]i = 0.38 +/- 0.06 mM, n = 5). The presence of extracellular sodium was required for magnesium exit. The initial rate of [Mg2+]i was stimulated by extracellular sodium with Michaelis-Menten kinetics. The Vmax of the sodium-dependent magnesium exit was markedly increased by [Mg2+]i. Holding the membrane potential at either -84 mV or at -10 mV had different effects on the sodium-stimulated magnesium efflux, depending on the extracellular sodium concentration ([Na+]o). At 10-30 mM [Na+]o, the magnesium efflux was faster at -10 mV than at -84 mV. Conversely, at 50-200 mM [Na+]o, the efflux of magnesium was faster at -84 mV that at -10 mV. At 75 mM [Na+]o, the activities where nearly the same at both membrane potential values. These observations suggest that the stochiometry of the Na+/Mg2+ exchange changes with [Na+]o.

Animals↗