RESUMEN
Testosterone is a nuclear androgen receptor ligand that controls multiple pathways in brain. In addition to the active biosynthesis of steroids in classic steroidogenic organs such as gonads, adrenals and placenta, testosterone also produced in astrocyte cells of brain. Testosterone and its level must be regulated in brain; because, it directly and indirectly affects memory and several key behavioral characteristics. The significance of sound waves on key enzymes that regulate levels of testosterone in brain has not been investigated. The aim of our study was to examine physical stress of such as sound on induction behavioral changes in animal models. According to the current study, sound waves with 528 Hz frequency in 100 dB intensity induce testosterone production in brain by enhancing StAR and SF-1 and reducing P450 aromatase gene expression. Frequency of 528 Hz also reduces total concentration of reactive oxidative species in brain tissue. Prolonged exposure to this sound wave showed reduction of anxiety related behaviors in rats. The results reveal that reduced anxiety is related to increased concentration of testosterone in brain. This study may lead to ascertain a possible therapy in which sounds may be utilized to reduce anxiety in individual.
Asunto(s)
Encéfalo/efectos de la radiación , Testosterona/metabolismo , Ondas Ultrasónicas , Animales , Aromatasa/genética , Aromatasa/metabolismo , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Encéfalo/citología , Encéfalo/metabolismo , Células Cultivadas , Masculino , Aprendizaje por Laberinto , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Factores de Empalme de ARN/genética , Factores de Empalme de ARN/metabolismo , Ratas , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Transfusional iron overload is a major cause of morbidity and mortality in thalassemia, sickle-cell disease and other chronic anemias. To overcome these problems, orally bio available iron chelators, deferiprone and deferasirox, were used for the treatment of patients suffering from thalassemia. The interactions between deferiprone and deferasirox with the carrier protein, beta-thalassemia hemoglobin (Hb), were investigated using fluorescence, circular dichroism (CD) and UV-visible measurements at physiological condition. Strong fluorescence quenching on interactions of the above drugs with beta-thalassemia Hb were observed. Fluorescence quenching data of thalassemia Hb in the presence of deferasirox have shown greater affinity of binding. The number of binding sites to Hb for deferasirox was found to be more relative to those of the deferiprone. The effects of these drugs on the oxygen affinity of the thalassemia Hb were studied by spectroscopic methods using sodium dithionite. Results indicated that deferiprone reduces oxygen affinity (increases oxygen releasing ability) of Hb, while in the presence of deferasirox, oxygen affinity of Hb has significantly increased by dose-dependent manner. As such, deferasirox exhibited opposite effect relative to deferiprone on the function of thalassemia Hb. In clinical dose of deferiprone, CD results showed that, the alpha-helical content of thalassemia Hb significantly increased. By use of the clinical dose of deferasirox, however, a decrease in alpha-helical content of protein was observed, which resulted in decreasing stability of thalassemia Hb. Our study showed that reduction in stability of thalassemia Hb in the presence of deferasirox induced higher conformational changes in protein.
Asunto(s)
Benzoatos/química , Hemoglobinas/química , Hemoglobinas/metabolismo , Quelantes del Hierro/química , Piridonas/química , Triazoles/química , Talasemia beta/metabolismo , Benzoatos/metabolismo , Dicroismo Circular , Deferasirox , Deferiprona , Humanos , Quelantes del Hierro/metabolismo , Piridonas/metabolismo , Espectrometría de Fluorescencia , Relación Estructura-Actividad , Triazoles/metabolismoRESUMEN
Chromatography of microtubule protein through 8% agarose at 4 and 31 degrees C demonstrated that tubulin oligomer was not dissociated to tubulin dimer and microtubule associated proteins by assembly temperatures. During chromatography, formation of microtubules was prevented by using 10 microM podophyllotoxin and/or 25 microM GTP. In the presence of 25 microM GTP, tubulin oligomer at 31 degrees C and microtubule protein retained the ability to polymerize. Evidence against dimer formation from tubulin oligomer was also obtained via a turbidity study of the initial events (the first 90 s) of microtubule assembly.
Asunto(s)
Microtúbulos/metabolismo , Tubulina (Proteína)/metabolismo , Animales , Bovinos , Cromatografía en Agarosa , Guanosina Trifosfato/farmacología , Técnicas In Vitro , Microtúbulos/efectos de los fármacos , Podofilotoxina/farmacología , Conformación Proteica , Temperatura , Tubulina (Proteína)/aislamiento & purificaciónRESUMEN
For microtubule assembly, the data reported here support an initial nucleation phase followed by a growth or elongation phase. The nucleation phase was not detected kinetically. Evidence for this step was given by the existence of the critical concentration and the dependence of the number of microtubules on oligomer concentration. Kinetic evidence indicated the existence of two consecutive steps in the growth phase of microtubules. The fast process increased and the slow one decreased with the concentration of microtubule protein. Similar kinetics were found upon recombination of tubulin oligomer and dimer which had been resolved by agarose chromatography. The fast process increased with oligomer and decreased with dimer concentration while the slow one depended positively on dimer concentration. Microtubules were formed when the oligomeric fraction only was employed. In contrast, under identical conditions, no microtubule formation was detected turbidimetrically or by electron microscopy from dimer alone. When dimer caused elongation of seed tubules, there was only one growth step with a rate constant of the same order of magnitude as the slow process for the other experiments.