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SourceAvailable from: Ricardo Felix[Show abstract] [Hide abstract]
ABSTRACT: Voltage-gated T-type Ca(2+) (CaV 3) channels mediate a number of physiological events in developing and mature cells, and are implicated in neurological and cardiovascular diseases. In mammals, there are three distinct T-channel genes (CACNA1G, CACNA1H, CACNA1I) encoding proteins (CaV 3.1-CaV 3.3) that differ in their localization as well as in molecular, biophysical, and pharmacological properties. The CACNA1G is a large gene that contains 38 exons and is localized in chromosome 17q22. Only basic characteristics of the CACNA1G gene promoter region have been investigated classifying it as a TATA-less sequence containing several potential transcription factor-binding motifs. Here, we cloned and characterized a proximal promoter region and initiated the analysis of transcription factors that control CaV 3.1 channel expression using the murine Cacna1g gene as a model. We isolated a ∼1.5 kb 5'-upstream region of Cacna1g and verified its transcriptional activity in the mouse neuroblastoma N1E-115 cell line. In silico analysis revealed that this region possesses a TATA-less minimal promoter that includes two potential transcription start sites and four binding sites for the transcription factor Sp1. The ability of one of these sites to interact with the transcription factor was confirmed by electrophoretic mobility shift assays. Consistent with this, Sp1 over-expression enhanced promoter activity while siRNA-mediated Sp1 silencing significantly decreased the level of CaV 3.1 protein and reduced the amplitude of whole-cell T-type Ca(2+) currents expressed in the N1E-115 cells. These results provide new insights into the molecular mechanisms that control CaV 3.1 channel expression. J. Cell. Physiol. © 2013 Wiley Periodicals, Inc.Journal of Cellular Physiology 05/2014; 229(5). DOI:10.1002/jcp.24432
Actas Dermo-Sifiliográficas 03/2014; 105(2):204–206. DOI:10.1016/j.ad.2013.02.002
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ABSTRACT: Peroral endoscopic myotomy has recently been developed and performed on patients with good results. To evaluate the technical feasibility of peroral endoscopic full-thickness and partial thickness myotomy in a porcine model. Eighteen criollo pigs were randomly assigned to 2 groups: group A (partial-thickness myotomy) and group B (full-thickness myotomy). The mucosal defect proximal to the myotomy site was left open. On the seventh postoperative day the pig was euthanized and follow-up surgical exploration was performed. The duration of each procedure, postoperative progression of the animal, complications, and anatomopathologic findings were registered. The procedure was viable in all the pigs. The mean surgery duration was 81±35.3min (group A 51.11±11.12, group B 111±22.61; P<.05). The main complication during myotomy was subcutaneous emphysema (16%). The histopathologic study of the group A surgical specimens reported complete circular myotomy in all cases, and complete circular and longitudinal myotomy was reported in 100% of the group B sample. The endoscopic myotomy technique is feasible. Endoscopic partial-thickness myotomy was associated with shorter surgery duration and better results during the intraoperative period and the 7-day follow-up.Revista de gastroenterologia de Mexico 11/2013; DOI:10.1016/j.rgmx.2013.08.002
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