Characterisation of Carotenoids Involved in the Xanthophyll Cycle

Carotenoids are known for versatile roles they play in living organisms; however, their most pivotal function is involvement in scavenging reactive oxygen species (ROS) and photoprotection. In plant kingdom, an important photoprotective mechanism, referred to as the xanthophyll cycle, has been developed by photosynthetic organism to avoid excess light that might lead to photoinhibition and inactivation of photosystems and induce the formation of reactive oxygen species (ROS), resulting in photodamage and long-term changes in the cells caused by oxidative stress. Apart from high-light driven enzymatic conversion of violaxanthin (Viola) to zeaxanthin (Zea) that occurs mostly in higher plants, mosses and lichens, other less known types of the xanthophyll cycle have been hitherto described. The work is aimed at summarising the current knowledge on the pigments engaged in the xanthophyll cycles operating in various organisms

Protective Role of a Donepezil-Huprine Hybrid against the β-Amyloid (1-42) Effect on Human Erythrocytes

Aβ(1-42) peptide is a neurotoxic agent strongly associated with the etiology of Alzheimer's disease (AD). Current treatments are still of very low effectiveness, and deaths from AD are increasing worldwide. Huprine-derived molecules have a high affinity towards the enzyme acetylcholinesterase (AChE), act as potent Aβ(1-42) peptide aggregation inhibitors, and improve the behavior of experimental animals. AVCRI104P4 is a multitarget donepezil-huprine hybrid that improves short-term memory in a mouse model of AD and exerts protective effects in transgenic Caenorhabditis elegans that express Aβ(1-42) peptide. At present, there is no information about the effects of this compound on human erythrocytes. Thus, we considered it important to study its effects on the cell membrane and erythrocyte models, and to examine its protective effect against the toxic insult induced by Aβ(1-42) peptide in this cell and models. This research was developed using X-ray diffraction and differential scanning calorimetry (DSC) on molecular models of the human erythrocyte membrane constituted by lipid bilayers built of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE). They correspond to phospholipids representative of those present in the external and internal monolayers, respectively, of most plasma and neuronal membranes. The effect of AVCRI104P4 on human erythrocyte morphology was studied by scanning electron microscopy (SEM). The experimental results showed a protective effect of AVCRI104P4 against the toxicity induced by Aβ(1-42) peptide in human erythrocytes and molecular models

A rhein-huprine hybrid protects erythrocyte membrane integrity against Alzheimer's disease related Abeta(1-42) peptide

Alzheimer's disease remains largely unknown, and currently there is no complete cure for the disease. New synthetic approaches have been developed to create multi-target agents, such as RHE-HUP, a rhein-huprine hybrid which can modulate several biological targets that are relevant to the development of the disease. While RHE-HUP has shown in vitro and in vivo beneficial effects, the molecular mechanisms by which it exerts its protective effect on cell membranes have not been fully clarified. To better understand RHE-HUP interactions with cell membranes, we used synthetic membrane models and natural models of human membranes. For this purpose, human erythrocytes and molecular model of its membrane built-up of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE) were used. The latter correspond to classes of phospholipids present in the outer and inner monolayers of the human erythrocyte membrane, respectively. Xray diffraction and differential scanning calorimetry (DSC) results indicated that RHE-HUP was able to interact mainly with DMPC. In addition, scanning electron microscopy (SEM) analysis showed that RHE-HUP modified the normal biconcave shape of erythrocytes inducing the formation of echinocytes. Moreover, the protective effect of RHE-HUP against the disruptive effect of Aβ(1-42) on the studied membrane models was tested. X-ray diffraction experiments showed that RHE-HUP induced a recovery in the ordering of DMPC multilayers after the disruptive effect of Aβ(1-42), confirming the protective role of the hybrid