29 research outputs found
Evaluating the SERCA2 and VEGF mRNAs as Potential Molecular Biomarkers of the Onset and Progression in Huntington's Disease
Abnormalities of intracellular Ca2+ homeostasis and signalling as well as the down-regulation
of neurotrophic factors in several areas of the central nervous system and in peripheral
tissues are hallmarks of Huntington\u2019s disease (HD). As there is no therapy for this hereditary,
neurodegenerative fatal disease, further effort should be made to slow the progression
of neurodegeneration in patients through the definition of early therapeutic interventions.
For this purpose, molecular biomarker(s) for monitoring disease onset and/or progression
and response to treatment need to be identified. In the attempt to contribute to the research
of peripheral candidate biomarkers in HD, we adopted a multiplex real-time PCR approach
to analyse the mRNA level of targeted genes involved in the control of cellular calcium homeostasis
and in neuroprotection. For this purpose we recruited a total of 110 subjects possessing
the HD mutation at different clinical stages of the disease and 54 sex- and agematched
controls. This study provides evidence of reduced transcript levels of sarco-endoplasmic
reticulum-associated ATP2A2 calcium pump (SERCA2) and vascular endothelial
growth factor (VEGF) in peripheral blood mononuclear cells (PBMCs) of manifest and premanifest
HD subjects. Our results provide a potentially new candidate molecular biomarker
for monitoring the progression of this disease and contribute to understanding some early
events that might have a role in triggering cellular dysfunctions in HD
A thyroid-specific nuclear protein essential for tissue-specific expression of the thyroglobulin promoter.
4Dichiaro sotto la mia responsabilità che R Lonigro e I Lonigro sono la stessa personanonenoneCivitareale D; Lonigro I; Sinclair A.J; Di Lauro R.Civitareale, D; Lonigro, Incoronata; Sinclair A., J; Di Lauro, R
The tissue-specific expression of the thyroglobulin gene requires interaction between thyroid-specific and ubiquitous factors
Thyroid-specific expression of the rat thyroglobulin gene is mediated by transcriptional control. Sufficient DNA sequence information to confer thyroid-specific expression to a heterologous gene is contained between positions -168 and +39. DNA-binding studies have demonstrated that this region interacts with two thyroid-specific factors (TTF-1 and TTF-2), and a ubiquitous factor (UFA). Here we have characterized three elements within the promoter, A, K, and C, which are important for promoter activity in thyroid cells. We have shown by mutational analysis that the interaction of TTF-1 with the A and C regions. UFA with the A region, and TTF-2 with the K region are required for full promoter activity. The complex interactions in the A region can be replaced by the substitution of the UFA/TTF-1-binding site with a high-affinity TTF-1 binding site. There is a correlation between the presence of TTF-1 and TTF-2 DNA-binding activities and the expression of thyroglobulin, which implies that the mechanism restricting thyroglobulin expression to thyroid cells is mediated through the control of the expression, or the activity, of TTF-1 and TTF-2
The tissue-specific expression of the thyroglobulin gene requires interaction between thyroid-specific and ubiquitous factors
Thyroid-specific expression of the rat thyroglobulin gene is mediated by transcriptional control. Sufficient DNA sequence information to confer thyroid-specific expression to a heterologous gene is contained between positions -168 and +39. DNA-binding studies have demonstrated that this region interacts with two thyroid-specific factors (TTF-1 and TTF-2), and a ubiquitous factor (UFA). Here we have characterized three elements within the promoter, A, K, and C, which are important for promoter activity in thyroid cells. We have shown by mutational analysis that the interaction of TTF-1 with the A and C regions. UFA with the A region, and TTF-2 with the K region are required for full promoter activity. The complex interactions in the A region can be replaced by the substitution of the UFA/TTF-1-binding site with a high-affinity TTF-1 binding site. There is a correlation between the presence of TTF-1 and TTF-2 DNA-binding activities and the expression of thyroglobulin, which implies that the mechanism restricting thyroglobulin expression to thyroid cells is mediated through the control of the expression, or the activity, of TTF-1 and TTF-2