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1.
Acta Vet Hung ; 60(2): 263-84, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22609997

RESUMEN

Oestrogen (E2) and thyroid hormones (THs) are key regulators of cerebellar development. Recent reports implicate a complex mechanism through which E2 and THs influence the expression levels of each other's receptors (ERs and TRs) to precisely mediate developmental signals and modulate signal strength. We examined the modulating effects of E2 and THs on the expression levels of their receptor mRNAs and proteins in cultured cerebellar cells obtained from 7-day-old rat pups. Cerebellar granule cell cultures were treated with either E2, THs or a combination of these hormones, and resulting receptor expression levels were determined by quantitative PCR and Western blot techniques. The results were compared to non-treated controls and to samples obtained from 14-day-old in situ cerebella. Additionally, we determined the glial effects on the regulation of ER-TR expression levels. The results show that (i) ER and TR expression depends on the combined presence of E2 and THs; (ii) glial cells mediate the hormonal regulation of neuronal ER-TR expression and (iii) loss of tissue integrity results in characteristic changes in ER-TR expression levels. These observations suggest that both E2 and THs, in adequate amounts, are required for the precise orchestration of cerebellar development and that alterations in the ratio of E2/THs may influence signalling mechanisms involved in neurodevelopment. Comparison of data from in vitro and in situ samples revealed a shift in receptor expression levels after loss of tissue integrity, suggesting that such adjusting/regenerative mechanisms may function after cerebellar tissue injury as well.


Asunto(s)
Estrógenos , Receptores de Hormona Tiroidea , Animales , Western Blotting , Cerebelo , Regulación de la Expresión Génica , Reacción en Cadena de la Polimerasa , Ratas
2.
Expert Rev Proteomics ; 6(2): 199-211, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19385945

RESUMEN

Protozoan parasites are a major threat to human health with millions of fatalities worldwide, especially in nonindustrialized countries. Currently, there is no cure for many of these parasitic diseases. Consequently, there is an imperative to find treatment targets and develop novel drugs based on the proteins encoded in the genomes of these parasites. Aquaporins, members of membrane proteins discovered and characterized within the past 20 years, are the mechanism through which water is transported through living membranes. The presence of aquaporins explains disease etiology related to water physiology and presents new pharmacogenomic targets. In this article, we review the literature on aquaporins found in Apicomplexan, Kinetoplastida and Microsporidia parasites as potential drug targets. Furthermore, by analyzing protein motion dynamics, we identify impediments that need to be surmounted for developing effective drugs targeting the aquaglyceroporin of Plasmodium falciparum, the causative agent of the most fatal form of human malaria.


Asunto(s)
Acuaporinas/química , Acuaporinas/metabolismo , Eucariontes/metabolismo , Animales , Antimaláricos/uso terapéutico , Eucariontes/efectos de los fármacos , Eucariontes/patogenicidad , Humanos , Modelos Biológicos , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/metabolismo , Plasmodium falciparum/patogenicidad , Estructura Secundaria de Proteína , Proteínas Protozoarias/química , Proteínas Protozoarias/metabolismo , Proteínas Protozoarias/uso terapéutico
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