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Brain mitochondria are fundamental to maintaining healthy functional brains, and their dysfunction is involved in age-related neurodegenerative disorders such as Alzheimer's disease (AD). In this study, we conducted a research on how both non-synaptic and synaptic mitochondrial functions are compromised at an early stage of AD-like pathologies and their correlation with putative changes on membranes lipid profile, using 3 month-old nontransgenic and 3xTg-AD mice, a murine model of experimental AD. Bioenergetic dysfunction in 3xTg-AD brains is evidenced by a decrease of brain ATP levels resulting, essentially, from synaptic mitochondria functionality disruption as indicated by declined respiratory control ratio associated with a 50% decreased complex I activity. Lipidomics studies revealed that synaptic bioenergetic deficit of 3xTg-AD brains is accompanied by alterations in the phospholipid composition of synaptic mitochondrial membranes, detected either in phospholipid class distribution or in the phospholipids molecular profile. Globally, diacyl- and lyso-phosphatidylcholine lipids increase while ethanolamine plasmalogens and cardiolipins content drops in relation to nontransgenic background. However, the main lipidomic mark of 3xTg-AD brains is that cardiolipin cluster-organized profile is lost in synaptic mitochondria due to a decline of the most representative molecular species. In contrast to synaptic mitochondria, results support the idea that non-synaptic mitochondria function is preserved at the age of 3 months. Although the genetically construed 3xTg-AD mouse model does not represent the most prevalent form of AD in humans, the present study provides insights into the earliest biochemical events in AD brain, connecting specific lipidomic changes with synaptic bioenergetic deficit that may contribute to the progressive synapses loss and the neurodegenerative process that characterizes AD. [ABSTRACT FROM AUTHOR]

Lamium album L. is an edible plant which is consumed raw or cooked, in particular in the Mediterranean and surrounding areas. It is also consumed as tea infusions and as a main component of food supplements, because of its pharmacological effects. Despite being consumed by humans for centuries, the chemical composition of L. album L. is far from being understood. In this study, a purified ethanolic extract (PEEL) was prepared and further analyzed by high performance liquid chromatography and electrospray mass spectrometry. Overall, verbascoside accounted for approximately half of the phenolic content of the extract, but this also contained other bioactive phenolic compounds herein detected for the first time in the genus, namely isoscutellarein derivatives. The latter included isoscutellarein-7- O -allosyl(1 → 2)glucoside, its O -methyl derivative, three acetyl derivatives of isoscutellarein- O -allosyl glucoside and one acetylated form of O -methylisoscutellarein-7- O -allosyl(1 → 2)glucoside. From those, the main isoscutellarein derivative was assigned to isoscutellarein-7- O -(6- O -acetyl-β-allosyl)(1 → 2)-β-glucoside, as confirmed by NMR. Altogether, isoscutellarein derivatives accounted for almost 30% of PEEL phenolics. Since verbascoside and isoscutellarein derivatives are main components of L. album L. ethanolic extract, their possible association to the health benefits of the plant is discussed. [ABSTRACT FROM AUTHOR]

Abstract Endoplasmic reticulum–mitochondria contact sites have been a subject of increasing scientific interest since the discovery that these structures are disrupted in several pathologies. Due to the emerging data that correlate endoplasmic reticulum–mitochondria contact sites function with known events of the apoptotic program, we aimed to dissect this interplay using our well-established model of acetic acid-induced apoptosis in Saccharomyces cerevisiae. Until recently, the only known tethering complex between ER and mitochondria in this organism was the ER–mitochondria encounter structure (ERMES). Following our results from a screening designed to identify genes whose deletion rendered cells with an altered sensitivity to acetic acid, we hypothesized that the ERMES complex could be involved in cell death mediated by this stressor. Herein we demonstrate that single ablation of the ERMES components Mdm10p, Mdm12p and Mdm34p increases the resistance of S. cerevisiae to acetic acid-induced apoptosis, which is associated with a prominent delay in the appearance of several apoptotic markers. Moreover, abrogation of Mdm10p or Mdm34p abolished cytochrome c release from mitochondria. Since these two proteins are embedded in the mitochondrial outer membrane, we propose that the ERMES complex plays a part in cytochrome c release, a key event of the apoptotic cascade. In all, these findings will aid in targeted therapies for diseases where apoptosis is disrupted, as well as assist in the development of acetic acid-resistant strains for industrial processes. Graphical Abstract Unlabelled Image Highlights • Lack of ERMES increases the yeast resistance to acetic acid-induced apoptosis. • Resistance is associated with a delay in the emergence of apoptotic markers. • Lack of ERMES components reduces chronological life-span of yeast. • Mdm10p and Mdm34p play a pivotal role in cytochrome c release from mitochondria. • Acetic acid induces ERMES-independent mitochondrial phosphatidylinositol decrease. [ABSTRACT FROM AUTHOR]

Thymus x citriodorus is a Lamiaceae plant extensively cultivated in the Mediterranean region and used for centuries in culinary and in traditional medicine. The present work describes the detailed phenolic composition of T. x citriodorus for the first time, by means of HPLC–DAD, ESI–MS and MSn and nuclear magnetic resonance (NMR) analyses. The ethanolic extract of T. x citriodorus was analyzed by reversed phase HPLC. The method of analysis was also validated concerning its linearity, instrumental and method precision (for repeatability, immediate precision and intermediate precision) and accuracy (absolute recovery study). The technique was combined with electrospray mass spectrometry in order to identify the phenolic compounds and the structure of the main phenolics was also confirmed by NMR analysis. The in-house validated HPLC–DAD method showed good linearity for the tested reference compounds as well as satisfactory repeatability and immediate precision values, for both instrument and method. Furthermore, the satisfactory results of intermediate precision analysis and recovery assays indicated that the chromatographic method could be used to quantify the main phenolic compounds of T. x citriodorus with adequate precision and accuracy. The extract was rich in rosmarinic acid (10.4±0.6mg/g extract) that is a widespread phenolic acid in Thymus plants, but also in luteolin-7-O-α-glucuronide (12±2mg/g extract), that was herein reported in Thymus for the first time. Other novel compounds comprised one eriodictyol dihexoside with O-glycosidic linkages, two eriodictyol-O-monohexosides, one quercetagetin dimethyl ether-O-hexoside, one naringenin-O-hexoside and chrysoeriol-7-β-O-glucoside. Having in mind the health-promoting properties reported in literature for some of the main polyphenols found in T. x citriodorus, we suggest that this plant has a high potential for being used as a functional food. [ABSTRACT FROM AUTHOR]

Abstract: The study of protein damage by oxidative processes and its influence on protein activity is central to understanding the deleterious effects of oxidative stress on biological systems. This paper will focus on the study of enzyme inactivation by oxidative modifications, utilizing α-amylase from Bacillus species. (BAA) as a model protein. Oxidative stress was induced using metal catalyzed oxidation (MCO). The enzymatic activity of BAA was correlated with the oxidative damage induced to the protein. Off-line nano-HPLC–MALDI-TOF/TOF-MS was used to characterize the oxidative modifications occurring to the protein. Additionally, semi-quantitative analysis was employed in order to evaluate the significance of the various oxidative modifications. BAA oxidation was found to be deleterious to its enzymatic activity. A total of 10 amino acid residues were found to have an oxidation degree above 50%, out of which eight were methionine and tryptophan. Residues in the proximity of key structural elements were found to be particularly susceptible to oxidation. The oxidative process was found to be governed by the nature of the amino acid residues side chain and, to a lesser extent, their location within the three dimensional structure of the protein. [Copyright &y& Elsevier]

Abstract: Novel π-extended porphyrins were obtained from the Diels–Alder reaction of meso-tetraarylporphyrins with a pyrazine o-quinodimethane derivative. [Copyright &y& Elsevier]