Known players, new interplay in atherogenesis: Chronic shear stress and carbamylated-LDL induce and modulate expression of atherogenic LR11 in human coronary artery endothelium.

In this study we examined whether low-density lipoprotein (LDL) receptor family members represent a link between blood flow characteristics and modified low-density lipoproteins involved in endothelial injury, a pivotal factor in atherogenesis. We demonstrated the expression of pro-atherogenic LDL receptor relative (LR11) for the first time in human coronary artery endothelial cells (HCAEC) in vitro and in vivo. Next, LR11 expression and regulation were explored in HCAEC cultured conventionally or on the inner surface of hollow fiber capillaries under exposure to shear stress for 10 days in the presence or absence of LDL.

Renal LRP2 expression in man and chicken is estrogen-responsive.

In mammals, low-density lipoprotein receptor-related protein-2 (LRP2) is an endocytic receptor that binds multiple ligands and is essential for a wide range of physiological processes. To gain new insights into the biology of this complex protein, we have initiated the molecular characterization of the LRP2 homolog from an oviparous species, the chicken (Gallus gallus). The galline LRP2 cDNA encodes a membrane protein of 4658 residues.

An inosine 5'-monophosphate dehydrogenase 2 single-nucleotide polymorphism impairs the effect of mycophenolic acid.

Mycophenolic acid (MPA) is a selective inhibitor of inosine 5'-monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme of de novo synthesis of guanine nucleotides. The isoenzyme IMPDH2 predominates in activated lymphocytes, and its inhibition by MPA is part of standard immunosuppressive regimens. Yet, there are significant unexplained differences in efficacy and tolerability among patients.

LDL receptor family: isolation, production, and ligand binding analysis.

Members of the low density lipoprotein receptor gene family have recently received particular attention because of their involvement not only in lipoprotein transport, but also in signal transduction pathways. The main characteristic feature of this protein group is their cysteine-rich ligand binding domain, which is able to bind many unrelated proteins, such as apolipoproteins, proteases, and protease/inhibitor complexes, signaling molecules such as reelin, and several other groups of proteins. The main challenges of studying these proteins in vitro are their extremely high content of disulfide bridges and the detergent-sensibility of their classical ligands, i.

Role of leptin in reproduction.

Purpose Of Review: This article focuses on recently gained knowledge concerning the different emerging aspects of the role of leptin in reproduction, through both its central hypothalamus-mediated and peripheral actions.

Recent Findings: As delineated in murine models, STAT3-independent signals triggered by the leptin receptor are clearly important in fertility, and candidate pathways such as those via phosphatidylinositol-3 kinase and extracellular signal-related kinase are implicated in leptin-regulated cascades. Another aspect whose importance has recently been revealed is that of the bioavailability of leptin in general, and the fate and action of carrier-bound versus free leptin at central and peripheral sites in particular.

Extracellular matrices of the avian ovarian follicle. Molecular characterization of chicken perlecan.

In egg-laying species, such as the chicken, the mode of transport of lipoprotein particles from the capillary plasma to endocytic receptors on the oocyte surface is largely unknown. Here we show by molecular characterization that the large prominent heparan sulfate proteoglycan of extracellular matrices, termed perlecan or HSPG2 (the product of the hspg2 gene), is a component of ovarian follicles that may participate in this process. However, although normally a major HSPG of basement membranes or basal laminae, in chicken follicles, perlecan is absent from the membranous structure between the theca interna and granulosa cell layers, which to date has been considered a bona fide basement membrane.

Disulfide-linked heterodimeric clusterin is a component of the chicken eggshell matrix and egg white.

Clusterin is a widely expressed secretory glycoprotein which is found in mammals as a disulfide-bonded alpha/beta heterodimer generated by cleavage of the single-chain precursor. In contrast, clusterin occurs in the chicken mainly as an intracellular single-chain form and is not observed in serum. The present report identifies chicken clusterin as a component of the eggshell.

A model for modulation of leptin activity by association with clusterin.

Transport, biological action, and clearance of leptin are subject to modulation by plasma components responsible for the formation of the so-called "bound" fraction of serum leptin. Candidates for modulators have been identified previously, but mechanisms for their action, and thus their physiological roles, have remained unclear. Here we have obtained evidence for a role of serum-borne clusterin in leptin biology and have delineated a possible mechanism for its action.

Receptor-mediated chicken oocyte growth: differential expression of endophilin isoforms in developing follicles.

Receptor-mediated endocytosis of yolk precursors via clathrin-coated structures is the key mechanism underlying rapid chicken oocyte growth. In defining oocyte-specific components of clathrin-mediated events, we have to date identified oocyte-specific yolk transport receptors, but little is known about the oocytes' supporting endocytic machinery. Important proteins implicated in clathrin-mediated endocytosis and recycling are the endophilins, which thus far have been studied primarily in synaptic vesicle formation; in the present study, as a different highly active endocytic system, we exploit rapidly growing chicken oocytes.

A secreted soluble form of ApoE receptor 2 acts as a dominant-negative receptor and inhibits Reelin signaling.

Specialized neurons throughout the developing central nervous system secrete Reelin, which binds to ApoE receptor 2 (ApoER2) and very low density lipoprotein receptor (VLDLR), triggering a signal cascade that guides neurons to their correct position. Binding of Reelin to ApoER2 and VLDLR induces phosphorylation of Dab1, which binds to the intracellular domains of both receptors. Due to differential splicing, several isoforms of ApoER2 differing in their ligand-binding and intracellular domains exist.

A minimal binding domain of the low density lipoprotein receptor family.

As more relatives of the low density lipoprotein receptor (LDLR) are discovered, defining their minimal binding domain(s) becomes a challenge. Here we have chosen the multifunctional chicken oocyte receptor for yolk deposition (termed LR8), and the pan-receptor ligand, receptor associated protein (RAP), as model systems to characterize a minireceptor using the phage display approach. Displayed fragments derived from the entire 819 residue LR8 molecule, followed by selection via panning on RAP, led to the definition of an 80 residue stretch LR8 minireceptor.

A xanthomatosis-susceptibility gene may exist in a Syrian family with familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is an autosomal-dominant inherited disorder characterized by high serum low-density lipoprotein (LDL)-cholesterol concentrations, xanthoma formation, and premature atherosclerosis. Homozygous individuals die of vascular disease as children or young adults; heterozygous persons are at high risk for premature cardiovascular death. Mutations in the LDL-receptor gene are responsible for FH.