New insights into the biogenesis of human high-density lipoproteins

PURPOSE OF REVIEW: The interest for the human HDL system was recently revived by the identification of the ABCA1 as a critical component in the formation and maintenance of plasma HDL levels. The present review focuses on recent progress in our understanding of the basic mechanisms underlying HDL biogenesis pathways. RECENT FINDINGS: Several novel mechanisms governing ABCA1/apoA-I interactions have recently been identified: apolipoprotein A-I activates ABCA1 phosphorylation through the cAMP/protein kinase A-dependent pathway; the majority of ABCA1 exists as a tetramer in human living cell, supporting the concept that the homotetrameric ABCA1 complex constitutes the minimum functional unit for the formation of nascent HDL particles; apolipoprotein A-I has been shown to have a recycling retroendocytic pathway with uptake and resecretion of the lipidated nascent HDL particles by the cell, most likely through the ABCA1 transporter pathway; there is evidence that the speciation of nascent HDL into pre-beta and alpha-HDL is linked to specific cell lines, and occurs by both ABCA1-dependent and independent pathways. SUMMARY: The fundamental mechanisms underlying the biogenesis, speciation and maturation of HDL remain complex and not well understood. Understanding the mechanisms governing HDL genesis at the cellular level could provide novel insights into the human atheroprotective system in health and disease.     

High Affinity S-Adenosylmethionine Plasma Membrane Transporter of Leishmania Is a Member of the Folate Biopterin Transporter (FBT) Family

S-Adenosylmethionine (AdoMet) is an important methyl group donor that plays a central role in many essential biochemical processes. The parasite Leishmania can both synthesize and transport AdoMet. Leishmania cells resistant to the antifolate methotrexate due to a rearrangement in folate biopterin transporter (FBT) genes were cross-resistant to sinefungin, an AdoMet analogue. FBT gene rearrangements were also observed in Leishmania major cells selected for sinefungin resistance. One of the rearranged FBT genes corresponded to the main AdoMet transporter (AdoMetT1) of Leishmania as determined by gene transfection and gene inactivation experiments. AdoMetT1 was determined to be a high affinity plasma membrane transporter expressed constitutively throughout the growth phases of the parasite. Leishmania cells selected for resistance or naturally insensitive to sinefungin had lower expression of AdoMetT1. A new function in one carbon metabolism, also a pathway of interest for chemotherapeutic interventions, is described for a novel class of membrane proteins found in diverse organisms.     

Effect of osmotic stress on <Emphasis Type="Italic">Myrtus communis</Emphasis> germination

The effects of water potential on germination were studied in four provenances of Myrtus from different bioclimatic zones in Tunisia. Water potential between 0 and −10 bars were obtained using polyethylene glycol 6000 (PEG-6000) solutions. Seeds were planted in Petri dishes full of sterile perlite, and kept for one month under 1500 lux light with 16h photoperiod and at 25°C. A low water potential induced a reduction in germination percentage and germination speed. Significant variations between the provenances were found even under control conditions, especially at the speed germination level. The provenances from humid regions were the most susceptible to water stress, and their germination percentage showed significant reductions at −8 bars. These differences in germination ability of provenances might be attributed to intraspecific variations resulting from the effects of natural selection and genetic pool background.     

Apolipoprotein A-I activates cellular cAMP signaling through the ABCA1 transporter

It has been suggested that the signal transduction pathway initiated by apoA-I activates key proteins involved in cellular lipid efflux. We investigated apoA-I-mediated cAMP signaling in cultured human fibroblasts induced with (22R)-hydroxycholesterol and 9-cis-retinoic acid (stimulated cells). Treatment of stimulated fibroblasts with apoA-I for short periods of time (相似文献   

Enhanced Chemokine Receptor Expression on Leukocytes of Patients with Alzheimer's Disease

Although primarily a neurological complaint, systemic inflammation is present in Alzheimer''s Disease, with higher than normal levels of proinflammatory cytokines and chemokines in the periphery as well as the brain. A gradient of these factors may enhance recruitment of activated immune cells into the brain via chemotaxis. Here, we investigated the phenotypes of circulating immune cells in AD patients with multi-colour flow cytometry to determine whether their expression of chemokine receptors is consistent with this hypothesis. In this study, we confirmed our previously reported data on the shift of early- to late-differentiated CD4+ T-cells in AD patients. The percentage of cells expressing CD25, a marker of acute T-cell activation, was higher in patients than in age-matched controls, and percentages of CCR6+ cells were elevated. This chemokine receptor is primarily expressed on pro-inflammatory memory cells and Th17 cells. The proportion of cells expressing CCR4 (expressed on Th2 cells) and CCR5 (Th1 cells and dendritic cells) was also greater in patients, and was more pronounced on CD4+ than CD8+ T-cells. These findings allow a more detailed insight into the systemic immune status of patients with Alzheimer''s disease and suggest possible novel targets for immune therapy.     

Quantitative analysis of ABCA1-dependent compartmentalization and trafficking of apolipoprotein A-I: implications for determining cellular kinetics of nascent high density lipoprotein biogenesis

The molecular mechanisms underlying the apoA-I/ABCA1 endocytic trafficking pathway in relation to high density lipoprotein (HDL) formation remain poorly understood. We have developed a quantitative cell surface biotinylation assay to determine the compartmentalization and trafficking of apoA-I between the plasma membrane (PM) and intracellular compartments (ICCs). Here we report that (125)I-apoA-I exhibited saturable association with the PM and ICCs in baby hamster kidney cells stably overexpressing ABCA1 and in fibroblasts. The PM was found to have a 2-fold higher capacity to accommodate apoA-I as compared with ICCs. Overexpressing various levels of ABCA1 in baby hamster kidney cells promoted the association of apoA-I with PM and ICCs compartments. The C-terminal deletion of apoA-I Delta(187-243) and reconstituted HDL particles exhibited reduced association of apoA-I with both the PM and ICCs. Interestingly, cell surface biotinylation with a cleavable biotin revealed that apoA-I induces ABCA1 endocytosis. Such endocytosis was impaired by naturally occurring mutations of ABCA1 (Q597R and C1477R). To better understand the role of the endocytotic pathway in the dynamics of the lipidation of apoA-I, a pulse-chase experiment was performed, and the dissociation (re-secretion) of (125)I-apoA-I from both PM and ICCs was monitored over a 6-h period. Unexpectedly, we found that the time required for 50% dissociation of (125)I-apoA-I from the PM was 4-fold slower than that from ICCs at 37 degrees C. Finally, treatment of the cells with phosphatidylcholine-specific phospholipase C, increased the dissociation of apoA-I from the PM. This study provides evidence that the lipidation of apoA-I occurs in two kinetically distinguishable compartments. The finding that apoA-I specifically mediates the continuous endocytic recycling of ABCA1, together with the kinetic data showing that apoA-I associated with ICCs is rapidly re-secreted, suggests that the endocytotic pathway plays a central role in the genesis of nascent HDL.     

Significance of freeze-drying in long term storage of date palm pollen

The authors attempt to determine the optimal conditions for maintaining long term viability of date palm pollen using a special method of freeze-drying. They have undertaken a systematic study of the viability over time of a sample of the same pollen stored and conserved under different conditions (freeze-drying, temperature, gaseous atmosphere and storage time).

The results are thoroughly analysed by means of different approaches of multiparametric modelisation. These numerical treatments permit us to:

Les auteurs ont déterminé, par une méthode particulière de lyophilisation, les conditions optimales permettant le maintien de la viabilité du pollen du palmier dattier (Phoenix dactylifera) à long terme. Une étude systématique a été réalisée sur des lots provenant d'un même échantillon de pollen conservé et stocké selon différentes conditions: (lyophilisation, température, atmosphère gazeuse et en fonction du temps de stockage).

Ils ont cherché à analyser de manière approfondie les résultats obtenus au moyen de plusieurs approches de modélisation multiparamétrique.

Ces traitements numériques ont permis:

1. demonstrate that such a phenomenon submits to the usual laws and can be modelled

2. propose a general approach for the study of the ageing of pollen with time and with respect to different conservation and storage conditions.

1. de démontrer qu'un tel phénomène obéit globalement à des lois statistiques simples, et qu'il est de ce fait modélisable

2. de proposer une approche plus générale du vieillissement des grains de pollen en fonction du temps et des conditions de conservation et de stockage.