High molecular weight homologues of gp91phox, the superoxide-generating subunit of phagocyte nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, have been identified in human (h) and Caenorhabditis elegans (Ce), and are termed Duox for “dual oxidase” because they have both a peroxidase homology domain and a gp91phox domain. A topology model predicts that the enzyme will utilize cytosolic NADPH to generate reactive oxygen, but the function of the ecto peroxidase domain was unknown. Ce-Duox1 is expressed in hypodermal cells underlying the cuticle of larval animals. To investigate function, RNA interference (RNAi) was carried out in C. elegans. RNAi animals showed complex phenotypes similar to those described previously in mutations in collagen biosynthesis that are known to affect the cuticle, an extracellular matrix. Electron micrographs showed gross abnormalities in the cuticle of RNAi animals. In cuticle, collagen and other proteins are cross-linked via di- and trityrosine linkages, and these linkages were absent in RNAi animals. The expressed peroxidase domains of both Ce-Duox1 and h-Duox showed peroxidase activity and catalyzed cross-linking of free tyrosine ethyl ester. Thus, Ce-Duox catalyzes the cross-linking of tyrosine residues involved in the stabilization of cuticular extracellular matrix.
Neuritic plaque core amyloid protein in Alzheimer's disease brain tissue was investigated for the extent of amino acid racemization. Long-lived human proteins exhibit racemization of certain amino acids over the course of a human lifetime. Purified core amyloid was found to contain relatively large proportions of D-aspartate and D-serine, suggesting that neuritic plaque amyloid is derived from a long-lived precursor protein. Alternatively, racemization of protein amino acids may be abnormally accelerated in Alzheimer's disease.
Lewis rats were used to determine the encephalitogenic activity of myelin basic protein of different species and of 45-residue fragments of basic protein. Basic protein from guinea pigs was more active than that from rats, and the fragments from the two species showed the same order of activity. Bovine basic protein was the least active of the intact proteins, and the respective fragment was inactive. Studies of serum-binding capacity did not support the hypothesis that blocking antibody played a role in this biological variation, whereas consideration of the amino acid sequences of the three fragments suggested that differences in primary structure, operating either at the sensitization or the effector phase of the immune response, could account for the variation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.