Ryan C. McCarthy

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The mechanism(s) of iron flux across the brain microvasculature endothelial cells (BMVEC) of the blood-brain barrier remains unknown. Although both hephaestin (Hp) and the ferrous iron permease ferroportin (Fpn) have been identified in BMVEC, their roles in iron efflux have not been examined. Using a human BMVEC line (hBMVEC), we have demonstrated that(More)
A sequence within the E2 domain of soluble amyloid precursor protein (sAPP) stimulates iron efflux. This activity has been attributed to a ferroxidase activity suggested for this motif. We demonstrate that the stimulation of efflux supported by this peptide and by sAPPα is due to their stabilization of the ferrous iron exporter, ferroportin (Fpn), in the(More)
We have used an in vitro model system to probe the iron transport pathway across the brain microvascular endothelial cells (BMVEC) of the blood-brain barrier (BBB). This model consists of human BMVEC (hBMVEC) and C6 glioma cells (as an astrocytic cell line) grown in a transwell, a cell culture system commonly used to quantify metabolite flux across a(More)
The mechanism(s) by which iron in blood is transported across the blood–brain barrier (BBB) remains controversial. Here we have examined the first step of this trans-cellular pathway, namely the mechanism(s) of iron uptake into human brain microvascular endothelial cells (hBMVEC). We show that hBMVEC actively reduce non-transferrin bound FeIII (NTBI) and(More)
For the identification and characterization of proteins harboring posttranslational modifications (PTMs), a "top down" strategy using mass spectrometry has been forwarded recently but languishes without tailored software widely available. We describe a Web-based software and database suite called ProSight PTM constructed for large-scale proteome projects(More)
UNLABELLED Current liposomal gene delivery systems predominately utilize cationic lipids, which efficiently bind and deliver DNA plasmid, but also result in nonspecific gene expression in lung and liver tissue. To improve specificity, a two-component delivery strategy employing neutral liposomes was used to target breast cancers positive for the human(More)
Iron transport across the blood-brain barrier (BBB) involves the cooperation of brain microvascular endothelial cells (BMVEC) and their neighboring astrocytes. Astrocytes secrete a soluble form of ceruloplasmin (sCp) which, in turn, acts to export iron from ferroportin (Fpn) on the basolateral surface of BMVEC. Although regulation of astrocyte sCp gene(More)
There are two barriers for iron entry into the brain: (1) the brain–cerebrospinal fluid (CSF) barrier and (2) the blood–brain barrier (BBB). Here, we review the literature on developmental iron accumulation by the brain, focusing on the transport of iron through the brain microvascular endothelial cells (BMVEC) of the BBB. We review the iron trafficking(More)
Protocols are described for the isolation of substantial (mg) amounts of a rosette inhibition test (RIT)-active polypeptide fraction from ovine placental extracts. The main component of the preparation is a 12K polypeptide which contains a highly reactive thiol group. Oxidation may occur during isolation with the result that the final preparation is a(More)
Previous studies have demonstrated that mycobacteria attach to fibronectin (FN). The attachment of mycobacteria to FN is considered to be biologically important in Mycobacterium bovis BCG therapy for superficial bladder cancer, initiation of delayed hypersensitivity to mycobacterial antigens, and the phagocytosis of mycobacteria by epithelial cells.(More)