Arantxa Rodríguez-Casado

FTIR microspectroscopic analysis of the effects of certain drugs on oxidative stress and brain protein structure

This study reports the changes in lipids and proteins of different brain areas of nicotine, D(+)‐amphetamine, and nicotine and D(+)‐amphetamine treated rats by monitoring lipid peroxidation and protein β‐sheet formation using infrared microspectroscopy. Compared with the untreated brain samples, the peroxide level is relatively higher in the amphetamine‐treated brain sections, both in the cortex and hippocampus area. However, this peroxide increase is attenuated when administering amphetamine plus nicotine. Analogous drug‐dependent trends for protein β‐sheet content are observed, which suggests a connection between lipid oxidation involved in oxidative stress and β‐sheet protein structure generally present in neurodegenerative diseases. The above property of nicotine is of interest, in the sense that it might reduce the production of β‐amyloid proteins in Alzheimers disease.

CONFORMATIONAL STRUCTURE AND BINDING MODE OF GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE TO TRNA STUDIED BY RAMAN AND CD SPECTROSCOPY

Recently it has been suggested that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) play a role in nuclear tRNA export. As the structural basis of binding of GAPDH to tRNA is as yet unknown, we have employed Raman and CD spectroscopy as probes of the solution structures of GAPDH from rabbit and tRNA(Phe) from brewers yeast. Additionally, we have obtained the Raman and CD spectra of GAPDH when bound to tRNA(Phe). In the complex we find the following results: (a) The most part of the tRNA(Phe) structure is conserved, but with a slight perturbation toward a B-like form. (b) No significant changes in the secondary structure of the protein upon binding are observed. (c) The surface enhanced Raman spectra are consistent with a GAPDH-tRNA(Phe) complex molecular model that involves the insertion of TRNA(Phe) into the GAPDH tetramer groove containing the R and P axes. (d) The specific interactions that occur between GAPDH and the tRNA(Phe) involve, mainly, stacking between nucleobases and aromatic amino-acid residues, and ionic interactions of basic amino-acid residues with phosphate groups of the ribose-phosphate backbone. The above stacking interactions are also supported by the significant relatedness that we have found between an amino-acid sequence (residues 303-308) of GAPDH and RNP2 binding motifs of some RNA binding proteins.

Spectroscopic study of conformational changes accompanying self-assembly of HCV core protein

Electron microscopy and infrared and Raman spectroscopy have been used here to study the morphology, size distribution, secondary and tertiary structures of protein particles assembled from a truncated hepatitis C virus (HCV) core protein covering the first 120 aa. Particles of pure protein, having similar morphology and size distribution of those of nucleocapsids found in sera from HCV‐infected patients, have been visualized for the first time. The secondary structure of these protein particles involve β‐sheet enrichment in relation to its protein monomer. Tertiary/quaternary structure has also been studied using the dynamics of H/D exchange. With this aim infrared spectra were measured as a function of H/D exchange time and subsequently analyzed by principal component analysis and two‐dimensional correlation spectroscopy. Temporal dynamics of exchange for these protein particles were as follows: arginine residues exchanged first, followed by turn and unordered structures, followed by β‐sheets which may act as linkers of protein monomers. Proteins 2007.

Defective Insulin Signalling, Mediated by Inflammation, Connects Obesity to Alzheimer Disease; Relevant Pharmacological Therapies and Preventive Dietary Interventions

BACKGROUND Recent evidence suggests that obesity, besides being a risk factor for cardiovascular events, also increases the risk of Alzheimers disease. Insulin resistance is common in all cases of obesity and appears to be the linkage between both diseases. Obesity, often associated with excessive fat and sugar intake, represents a preclinical stage toward insulin resistance during which nutrition intervention is likely to have maximum effect. OBJECTIVE In this way, healthy lifestyles lifetime to prevent obesity-related modifiable risk factors such as inflammation, oxidative stress and metabolic disorders could be simultaneously beneficial for preserving cognition and controlling the Alzheimers disease. METHOD This review relates extensive research literature on facts linking nutrients and dietary patterns to obesity and Alzheimers disease. In addition briefly presents molecular mechanisms involved in obesity- induced insulin resistance and the contribution of peripheral inflammatory and defective insulin signalling pathways, as well as ectopic lipids accumulation to Alzheimers development through brain inflammation, neuronal insulin resistance, and cognitive dysfunction seen in Alzheimers disease. RESULTS The work relates current and emerging pharmacological and non-pharmacological therapies for the management of obesity, insulin resistance and Alzheimers considering them as disorders with common molecular features. CONCLUSION The findings of this review validate the importance of some nutritional interventions as possible approach to prevent or delay simultaneously progression of Alzheimers disease and obesity.

Raman Spectra of Alkali and Alkaline Earth Metal Salts of Inosine 5′‐Monophosphoric Acid

Crystalline Li(I), Na(I), K(I), Mg(II), Ca(II), Sr(II), Ba(II) and Cd(II) salts of inosine 5′-monophosphoric acid, H2(IMP), were obtained and characterized by Raman spectroscopy. Splitting of the imidazolic 1480 cm−1 band was observed for the N(7)-bound Ca(IMP)·6H2O, Ba(IMP)·6H2O, Sr(IMP)·6H2O and Cd(IMP)·4H2O compounds. The Li(I), Mg(II), Ca(II) and Cd(II) ions bind directly to the phosphate group, and no direct coordination involving the carbonyl C(6)O group was observed in the compounds reported here. Some Raman spectral features in the 750–700 cm−1 range seem to reflect the nucleoside structure of the inosine moiety

Raman and CD spectroscopy of the interaction between tRNA and glyceraldehyde-3-phosphate dehydrogenase

A variety of diverse biological properties of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) have been reported recently over a series of independent studies, these properties including membrane, cytoplasmic and nuclear functions in endocytosis, mRNA regulation, tRNA export DNA replication and DNA repair [1–3]. Concerning nuclear tRNA export, we know relatively little about its underlying mechanism. We have employed here Raman spectroscopy as a probe of the solution structure of GAPDH, tRNA and their complex in order to get information about the mechanism of the interaction between both biomolecules.

Infrared Spectroscopic Study of 18O(6)-Guanosbve

Infrared spectroscopy has proved to be a valuable tool in the structural investigation of nucleosides and nucleotides. One of the most important characteristics of vibrational spectra is the localization of some of the vibrations in the molecule in particular atoms or atomic groupings, permitting the assignment of some absorption bands to particular parts of the molecule. Previous works made to interpret the vibrational spectra of guanine derivatives only led to assignments of characteristic frequencies using 15N and D-substituted guanines [1–3]. Additional investigation on the nucleoside guanosine is necessary in order to know the vibrational modes involving the purine carbonyl group and to understand the possible coupling between different carbonyl groups in nucleic acid duplexes and triplexes. For this purpose we have used 18O isotopic substitution of the O(6) carbonyl oxygen.