The present studies were conducted to determine whether prostaglandin F2a (PGF2a) stimulates the production of "second messengers" derived from inositol phospholipid hydrolysis and increases intracellular free Ca2+ ([Ca2+],) in isolated bovine luteal cells. PGF2. provoked rapid (10 sec) and sustained (up to 60 min) increases in the levels of inositol mono-, bis-, and trisphosphates (InsP, InsP2, and InsP3, respectively PGF2a-induced increases in [Ca2+], were also independent of extracellular calcium. These findings demonstrate that the action of PGF2a is coupled to the phospholipase C-InsP3 and diacylglycerol second messenger system in the corpus luteum.The ability of prostaglandin F2a (PGF2a) to cause a loss of function of the corpus luteum was demonstrated over 15 years ago (1,2), but the precise mechanism of action of PGF2, remains unknown. PGF2a-induced luteolysis is correlated with changes in luteal membrane lipid composition and reductions of membrane fluidity (3-6), which have been suggested to prevent gonadotropin receptor aggregation (7) and the association and coupling to adenylate cyclase (8-10). PGF2a also acts at postreceptor sites to inhibit steroidogenesis (10, 11). Behrman and coworkers (12,13)
We report a new class of peptide mimetics, α-AApeptides, that display broad-spectrum activity against both Gram-negative and Gram-positive bacteria and fungi. With non-hemolytic activity, resistance to protease hydrolysis, and easy sequence programmability, α-AApeptides may emerge as a novel class of antibiotics.
The FACE technology is a powerful tool for analysis of all four classes of glycosaminoglycans obtained from a wide variety of biologic sources. While the FACE protocols are relative simple, they provide a wealth of information including quantitation in the pmole range, determination of fine structure, and estimation of chain length.
Chondroitin lyase products of aggrecan and small proteoglycans from normal and osteoarthritic cartilages were analyzed for chain internal ⌬disaccharides and terminal mono-or disaccharides. Chondroitin and dermatan sulfate chains from arthritic cartilages were of essentially normal size and internal sulfation but had significantly altered sulfation of the terminal residues. Whereas in normal cartilage, ϳ60% of terminal GalNAc4S was 4,6-disulfated, it was reduced to ϳ30% in osteoarthritic cartilage. This is most likely due to a lower terminal GalNAc4,6S-disulfotransferase activity and reveals that metabolic changes in osteoarthritis can affect this distinct sulfation step during chondroitin and dermatan sulfate synthesis. GlcA1,3GalNAc6S-, the mimotope for antibody 3B3(؊), was present on ϳ8 and ϳ10% of chains from normal and osteoarthritic cartilages, respectively. 3B3(؊) assayed by immunodot blot was within the normal range for most osteoarthritic samples, with only 5 of 24 displaying elevated reactivity. This resulted not from a higher content of mimotope, but possibly from other structural changes in the proteoglycan that increase mimotope reactivity. In summary, chemical determination of sulfation isomers at the non-reducing termini of chondroitin and dermatan sulfate provides a reliable assay for monitoring proteoglycan metabolism not only during normal growth of cartilage but also during remodeling of cartilage in osteoarthritis.The function of normal adult joint cartilage resides in its ability to provide resistance to compressive, tensile, and shear forces that occur during normal joint motion. The specialized extracellular matrix consists of a fibrillar collagen network (1), highly organized and stabilized through inter-and intramolecular cross-links that restrain the swelling pressure exerted by the high concentration of negatively charged aggrecan aggregates (2). The metabolic activity of chondrocytes in adult cartilage is adapted to maintain the composition of a functional extracellular matrix. The collagen network is relatively metabolically inert (3), whereas other constituents, such as aggrecan aggregates, undergo a distinct turnover process (4, 5) in which catabolic cleavage (6, 7) and removal of molecules from the extracellular matrix (8, 9) are in balance with synthesis and deposition of new molecules. However, at the onset and throughout progression of degenerative joint disease, such as OA, 1 this metabolic balance is perturbed, and episodes of increased catabolism (10, 11) and increased synthesis (12-16) of matrix components by the chondrocyte take place.It has been proposed that the increased anabolic activity in OA is related to a change in the differentiated state of the chondrocyte (17) with expression of pathways that are characteristic of cells in fetal or postnatal growth cartilages. This hypothesis has been particularly supported by published reports (18 -21) that the GAG composition of aggrecan synthesized during the early stages of cartilage degeneration in animal models of OA or ac...
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