Browsing by Author "Vasquez, Rodrigo"
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- ItemD-Glucose stimulation of L-arginine transport and nitric oxicle synthesis results from activation of mitogen-activated protein kinases p42/44 and smad2 requiring functional type II TGF-beta receptors in human umbilical vein endothelium(WILEY, 2007) Vasquez, Rodrigo; Farias, Marcelo; Vega, Jost Luis; Martin, Rody San; Vecchiola, Andrea; Casanello, Paola; Sobrevia, LuisElevated extracellular D-glucose increases transforming growth factor P I (TGF-P 1) release from human umbilical vein endothelium (HUVEC). TGF-P 1, via TGF-P receptors I (T beta RI) and T beta RII, activates Smad2 and mitogen -activated protein kinases p44 and p42 (p42/44 (mapk)). We studied whether D-glucose-stimulation Of L-arginine transport and nitric oxide synthesis involves TGF-beta 1 in primary cultures of HUVEC. TGF-P I release was higher (similar to 1.6-fold) in 25 mM (high) compared with 5 mM (normal) D-glucose. TGF-P I increases L-arginine transport (half maximal effect similar to 1.6 ng/ml) in normal D-glucose, but did not alter high D-glucose-increased L-arginine transport. TGF-P I and high D-glucose increased hCAT- I mRNA expression (similar to 8-fold) and maximal transport velocity (V-max), L- [(3) H]citrulline formation from L- [3 H]arginine (index of NO synthesis) and endothelial NO synthase (eNOS) protein abundance, but did not alter eNOS phosphorylation. TGF-beta 1 I and high D-gludose increased p42/44 mapk and Smad2 phosphorylation, an effect blocked by PD-98059 (MEK 1 /2 inhibitor). However, TGF-P I and high D-glucose were ineffective in cells expressing a truncated, negative dominant T beta RII High D-glucose increases L-arginine transport and eNOS expression following T beta RII activation by TGF-P I involving p42/44 (mapk) and Smad2 in HUVEC. Thus, TGF-P I could play a crucial role under conditions of hyperglycemia, such as gestational diabetes mellitus, which is
- ItemIn vivo micro computed tomography detection and decrease in amyloid load by using multifunctionalized gold nanorods: a neurotheranostic platform for Alzheimer's disease(Royal Soc Chemistry, 2021) Morales Zavala, Francisco; Jara Guajardo, Pedro; Chamorro Veloso, David Daniel; Riveros, Ana L.; Chandia Cristi, América Valeska; Salgado Cortés, Nicole Andrea; Pismante, Paola; Giralt, Ernest; Sanchez Navarro, Macarena; Araya, Eyleen; Vasquez, Rodrigo; Acosta, Gerardo; Albericio, Fernando; Alvarez, Alejandra R.; Kogan, Marcelo J.The development and use of nanosystems is an emerging strategy for the diagnosis and treatment of a broad number of diseases, such as Alzheimer's disease (AD). Here, we developed a neurotheranostic nanosystem based on gold nanorods (GNRs) that works as a therapeutic peptide delivery system and can be detected in vivo for microcomputed tomography (micro-CT), being a diagnostic tool. GNRs functionalized with the peptides Ang2 (a shuttle to the Central Nervous System) and D1 (that binds to the A beta peptide, also inhibiting its aggregation) allowed detecting differences in vivo between wild type and AD mice (APPswe/PSEN1dE9) 15 minutes after a single dose by micro-CT. Moreover, after a recurrent treatment for one month with GNRs-D1/Ang2, we observed a diminution of amyloid load and inflammatory markers in the brain. Thus, this new designed nanosystem exhibits promising properties for neurotheranostics of AD.
- ItemPeptide multifunctionalized gold nanorods decrease toxicity of beta-amyloid peptide in a Caenorhabditis elegans model of Alzheimer's disease(2017) Morales Zavala, Francisco; Arriagada, Hector; Hassan, Natalia; Velasco, Carolina; Riveros, Ana; Álvarez Rojas, Alejandra; Nogueras de Minniti, Alicia Susana; Rojas Silva, Ximena; Muñoz, Luis L.; Vasquez, Rodrigo