Excessive mucus production by airway epithelium is a major characteristic of a number of respiratory diseases, including asthma, chronic bronchitis, and cystic fibrosis. However, the signal transduction pathways leading to mucus production are poorly understood. Here we examined the potential role of IB kinase  The airway epithelium is the first layer of cellular interaction with airborne antigens and plays a key role in initiating allergic responses. Research over the last decade has established a critical role for the epithelium not only by providing a physical boundary but also in transducing and integrating signals that help mount optimal responses to a wide variety of insults (1-3). Airway mucus is a highly hydrated glycoprotein exhibiting a gel state and, in combination with the ciliated cells in the airways, constitutes a mucociliary clearance system critical for protection of the respiratory tract (4). The apoprotein component of mucus is the product of a family of mucin genes (generally referred to as MUC
Absence of functional presenilin 1 (PS1) protein leads to loss of ␥-secretase cleavage of the amyloid precursor protein (APP), resulting in a dramatic reduction in amyloid  peptide (A) production and accumulation of ␣-or -secretase-cleaved COOH-terminal fragments of APP (␣-or -CTFs). The major COOH-terminal fragment (CTF) in brain was identified as APP-CTF-(11-98), which is consistent with the observation that cultured neurons generate primarily A-(11-40). In PS1 ؊/؊ murine neurons and fibroblasts expressing the loss-offunction PS1 D385A mutant, CTFs accumulated in the endoplasmic reticulum, Golgi, and lysosomes, but not late endosomes. There were some subtle differences in the subcellular distribution of CTFs in PS1 ؊/؊ neurons as compared with PS1 D385A mutant fibroblasts. However, there was no obvious redistribution of full-length APP or of markers of other organelles in either mutant. Blockade of endoplasmic reticulum-to-Golgi trafficking indicated that in PS1؊/؊ neurons (as in normal cells) trafficking of APP to the Golgi compartment is necessary before ␣-and -secretase cleavages occur. Thus, although we cannot exclude a specific role for PS1 in trafficking of CTFs, these data argue against a major role in general protein trafficking. These results are more compatible with a role for PS1 either as the actual ␥-secretase catalytic activity or in other functions indirectly related to ␥-secretase catalysis (e.g. an activator of ␥-secretase, a substrate adaptor for ␥-secretase, or delivery of ␥-secretase to APP-containing compartments).The presenilin 1 (PS1) 1 and presenilin 2 (PS2) genes encode polytopic transmembrane proteins (1, 2), which are components of high molecular weight, multimeric protein complexes predominantly located in the nuclear envelope, endoplasmic reticulum (ER), Golgi, and selected intracellular vesicular structures (3-9). These proteins play major roles in controlling the proteolytic processing of Notch and the -amyloid precursor protein (APP) (10 -15). Absence of PS1 is associated with failure of ␥-secretase-mediated cleavage of the COOH-terminal fragments (CTFs) generated by ␣-or -secretase cleavage of the APP (10 -12). Thus, PS1 deficiency results in accumulation of the CTFs of APP and a dramatic reduction in A production.The mechanism by which absence of PS1 function causes loss of ␥-secretase activity is unclear; but the observations that 1) mutation of two transmembrane aspartate residues in PS1 (Asp 257 and Asp 385 ) causes loss of ␥-secretase cleavage; and 2) transition state aspartyl protease inhibitors, which block ␥-secretase activity bind to PS1 and PS2 (16,17), have led to speculation that PS1 may itself be a novel aspartyl protease with ␥-secretase activity (18). However, we have recently observed that aspartyl mutants disrupt the maturation of PS1 into high molecular weight functional complexes (19). Consequently, alternate explanations for the roles of PS1 in the processing of type 1 transmembrane proteins like APP and Notch must be formally evaluated (1...
The crossed-lamellar microarchitecture (microstructure) of the shell of Strombus gigas, the giant Queen conch native to Caribbean habitats, is the most common of the several shell microarchitectures known in the mollusk family. We have studied tissue regeneration in juvenile S. gigas conchs and compared the microstructure in this regenerated tissue to the microstructure of wild S. gigas shells. The regenerated hard tissue was of two types: hard tissue grown during wound repair, and so-called "flat pearls" which are hard tissue grown on abiotic substrates inserted between the mantle and the outer covering. In both cases, the crossed-lamellar microstructure is observed after formation of a transition structure consisting of a large quantity of matrix and aggregates of aragonite crystallites.
OxLDL inhibits endothelial cell migration, and may impair healing of arterial injuries. The mechanism of oxidized LDL inhibition is not known. Our in vitro studies show that the inhibitory properties are related to production of reactive oxygen species. Superoxide dismutase or inhibitors of reduced nicotinamide adenine dinucleotide phosphate oxidase can preserve endothelial migration in the presence of oxLDL. This might improve the healing of endothelial injuries at sites of arterial repair or angioplasty, especially in lipid-laden arterial walls.
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