Many proteins have been proposed to act as surrogate markers of organ damage, yet for many candidates the essential biomarker characteristics that link the protein to the injured organ have not yet been described. We generated an Ngal reporter mouse by inserting a double-fusion reporter gene encoding luciferase-2 and mCherry (Luc2-mC) into the Ngal (Lcn2) locus. The Ngal-Luc2-mC reporter accurately recapitulated the endogenous message and illuminated injuries in vivo in real time.
View Article and Find Full Text PDFThe lipocalins are secreted proteins that bind small organic molecules. Scn-Ngal (also known as neutrophil gelatinase associated lipocalin, siderocalin, lipocalin 2) sequesters bacterial iron chelators, called siderophores, and consequently blocks bacterial growth. However, Scn-Ngal is also prominently expressed in aseptic diseases, implying that it binds additional ligands and serves additional functions.
View Article and Find Full Text PDFNeutrophil gelatinase-associated lipocalin (NGAL) is expressed and secreted by immune cells, hepatocytes, and renal tubular cells in various pathologic states. NGAL exerts bacteriostatic effects, which are explained by its ability to capture and deplete siderophores, small iron-binding molecules that are synthesized by certain bacteria as a means of iron acquisition. Consistently, NGAL deficiency in genetically modified mice leads to an increased growth of bacteria.
View Article and Find Full Text PDFCurr Opin Nephrol Hypertens
July 2006
Purpose Of Review: Neutrophil gelatinase-associated lipocalin (NGAL) is a member of the lipocalin superfamily of carrier proteins. NGAL is the first known mammalian protein which specifically binds organic molecules called siderophores, which are high-affinity iron chelators. Here, we review the expression, siderophore-dependent biological activities and clinical significance of NGAL in epithelial development and in kidney disease.
View Article and Find Full Text PDFGlutamate transporters may exist as homomultimers, but little is known about the mechanisms that ensure proper assembly and surface expression. In the present study, we investigated the mechanisms that contribute to posttranslational processing of the GLT-1 subtype of glutamate transporter. An extracellular leucine-based motif was identified that after mutation to alanine (6L/6A GLT-1) prevented export of GLT-1 from the endoplasmic reticulum (ER) to the plasma membrane and displayed a glycosylation pattern characteristic of "immature" transporter.
View Article and Find Full Text PDFNa(+)-dependent glutamate transporters are required for the clearance of extracellular glutamate and influence both physiological and pathological effects of this excitatory amino acid. In the present study, the effects of a protein kinase C (PKC) activator on the cell surface expression and activity of the GLT-1 subtype of glutamate transporter were examined in two model systems, primary co-cultures of neurons and astrocytes that endogenously express GLT-1 and C6 glioma cells transfected with GLT-1. In both systems, activation of PKC with phorbol ester caused a decrease in GLT-1 cell surface expression.
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