1,721,089 research outputs found
Is there evidence that H2S (like CO and NO) may be a neuromodulator? If it is, what is the mechanism of its action?
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Structure-function relationship of estrogen receptor α and β: impact on human health
No full text17b-Estradiol (E2) controls many aspects of human physiology, including development,
reproduction and homeostasis, through regulation of the transcriptional activity of its cognate
receptors (ERs). The crystal structures of ERs with agonists and antagonists and the use of
transgenic animals have revealed much about how hormone binding influences ER conformation(
s) and how this conformation(s), in turn, influences the interaction of ERs with co-activators
or co-repressors and hence determines ER binding to DNA and cellular outcomes. This
information has helped to shed light on the connection between E2 and the development or
progression of numerous diseases. Current therapeutic strategy in the treatment of E2-related
pathologies relies on the modulation of ER trancriptional activity by anti-estrogens; however,
data accumulated during the last five years reveal that ER activities are not only restricted to
the nucleus. ERs are very mobile proteins continuously shuttling between protein targets
located within various cellular compartments (e.g., membrane, nucleus). This allows E2 to
generate different and synergic signal transduction pathways (i.e., non-genomic and genomic)
which provide plasticity for cell response to E2. Understanding the structural basis and the
molecular mechanisms by which ER transduce E2 signals in target cells will allow to create
new pharmacologic therapies aimed at the treatment of a variety of human diseases affecting the cardiovascular system, the reproductive system, the skeletal system, the nervous system,
the mammary gland, and many others
Structure-function relationship of estrogen receptor alpha and beta: impact on human health
No full textCatalytic properties of cysteine proteinases from Trypanosoma cruzi and Leishmania infantum: a pre-steady-state and steady-state study
No full textThiol disulfide exchange reactions in human serum albumin: the apparent paradox of the redox transitions of Cys34
Full text linkHuman serum albumin (HSA) is characterized by 17 disulfides and by only one unpaired cysteine (Cys(34)), which can be free in the reduced albumin or linked as a mixed disulfide with cysteine, or in minor amount with other natural thiols, in the oxidized albumin. In healthy subjects, the level of the oxidized form is about 35%, but it rises up to 70% after oxidative insults or in patients with kidney diseases. Oxidized albumin is therefore considered a short-term biomarker of oxidative stress as its level may increase or decrease under appropriate redox inputs in discrete temporal spans. This paper defines, for the first time, the kinetic properties of reduced and oxidized Cys(34) of HSA in their reactions with natural disulfides and thiols. Kinetic constants support the evidence that the Cys(34) redox oscillations observed in vivo are mainly due to the interaction with cysteine and cystine without the involvement of any enzymatic support. This study gives also a plausible explanation for the absence of involvement of the 17 disulfides naturally present in HSA in these redox transitions. This inert behavior toward cysteine is marginally due to solvent accessibility or flexibility factors of these bonds but mainly to their strong thermodynamic stability, which is caused essentially by a proximity effect. A similar mechanism is likely at play in the many proteins that maintain disulfide bridges in a reducing medium like the cytosol
Nitrosylation of rabbit ferrous heme-hemopexin
No full textHemopexin (HPX) serves as a trap for toxic plasma heme, ensuring its complete clearance by transportation to the liver. Moreover, HPX-heme has been postulated to play a key role in the homeostasis of nitric oxide (NO). Here, the thermodynamics for NO binding to rabbit ferrous HPX-heme as well as the EPR and optical absorption spectroscopic properties of rabbit ferrous nitrosylated HPX-heme (HPX-heme-NO) are reported. The value of the dissociation equilibrium constant for NO binding to rabbit ferrous HPX-heme (i.e., H) is (1.4±0.2)×10–7 M, at pH 7.0 and 10.0 °C; the value of H is unaffected by sodium chloride. At pH 7.0, rabbit ferrous HPX-heme-NO is a six-coordinate heme-iron species, characterized by an X-band EPR spectrum with an axial geometry and by =146 mM–1 cm–1 at 419 nm. At pH 4.0, rabbit ferrous HPX-heme-NO is a five-coordinate heme-iron species, characterized by an X-band EPR spectrum with three-line splitting centered at 334 mT and by =74 mM–1 cm–1 at 387 nm. The pKa value of the reversible pH-induced six- to five-coordinate spectroscopic transition is 4.8±0.1 in the absence of sodium chloride and 4.3±0.1 in the presence of 1.5×10–1 M sodium chloride. This result is in agreement with the effect of sodium chloride on rabbit HPX-heme stability. The present data have been analyzed in parallel with those of a related heme model compound and heme-protein systems
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