No abstract

In humans, blockade of the renin-angiotensin system with angiotensin converting-enzyme inhibitors (ANG CEI) prevents the rise in blood pressure associated with the administration of recombinant human erythropoietin (rhEPO). This study was conducted to determine whether rhEPO elevates blood pressure in normal Wistar rats and whether the renin-ANG system is affected. Groups of 10 rats each were given rhEPO, ANG CEI (enalapril), rhEPO + ANG CEI, or vehicle. Renin and/or renin substrate mRNA was measured in aortas, kidney, and heart; renin activity (PRA), inactive renin, and renin substrate were measured in plasma. rhEPO raised blood pressure in the normal rat without changing the plasma renin system. ANG CEI prevented this blood pressure rise. Renin-specific mRNA was increased by rhEPO in renal tissue, and renin substrate mRNA was significantly elevated in the kidney and aorta. mRNA for renin and renin substrate were not altered in the heart. In both aorta and kidney, a significant correlation was observed between renin substrate mRNA and blood pressure. The data indicate that rhEPO modulates specific tissue renin-ANG systems, which may contribute to blood pressure elevation.

The tight junction has been characterized as a domain of focal fusions of the exoplasmic leaflets of the lipid bilayers from adjacent epithelial cells. Approximating membranes to within fusion distance is a thermodynamically unfavorable process and requires the participation of membrane-bridging or -fusion proteins. No known tight junction protein exhibits such activities. Annexin A2 (A2), in particular its heterotetramer (A2t), is known to form junctions between lipid bilayer structures through molecular bridging of their external leaflets. We demonstrate abundant A2 expression in Madin-Darby canine kidney II monolayers by two-dimensional gel electrophoresis. Confocal immunofluorescence microscopic analysis suggests the bulk of A2 is located along the apical and lateral plasma membrane in its tetrameric configuration, consisting of two A2 and two p11 (an 11-kDa calmodulin-related protein, S100A10) subunits. Immunocytochemistry and ultrastructural immunogold labeling demonstrate colocalization of the A2 subunit with bona fide tight junction proteins, zonula occludens-1, occludin, and claudin-1, at cell-cell contacts. The extracellular addition of a synthetic peptide, targeted to disrupt the binding between A2 and p11, completely aborts tight junction assembly in calcium chelation studies. We propose A2t as a member of a new class of tight junction proteins responsible for the long-observed convergence of adjacent exoplasmic lipid leaflets in tight junction assembly.

Available information supports the dominance of the proximal intestine in inorganic phosphate (Pi) Pi. This approach allows the analysis of the mechanism and the regulation of Pi absorption under more authentic in vivo conditions. (J. Clin. Invest. 1993. 91:915-922.)

The epithelial tight junction (TJ) was first described ultrastructurally as a fusion of the outer lipid leaflets of the adjoining cell membrane bilayers (hemifusion). The discovery of an increasing number of integral TJ and TJ-associated proteins has eclipsed the original lipid-based model with the wide acceptance of a protein-centric model for the TJ. In this review, we stress the importance of lipids in TJ structure and function. A lipid-protein hybrid model accommodates a large body of information supporting the lipidic characteristics of the TJ, harmonizes with the accumulating evidence supporting the TJ as an assembly of lipid rafts, and focuses on an important, but relatively unexplored, field of lipid-protein interactions in the morphology, physiology, and pathophysiology of the TJ.