ubiquinone and juglone

The fragment of tau containing the first and third tubulin-binding motifs, involved in self-assembly of tau, was phosphorylated by protein kinase A (PKA). In the presence of hydroxynonenal (HNE) or in the presence of quinones such as juglone, 2,3-dimethoxy-5-methyl-1,4-benzoquinone (coenzyme Q(0) or DMM), or menadione, the polymerization of this phosphorylated tau fragment is catalyzed, whereas polymerization of the unmodified fragment takes place in a lesser extent. The quinones coenzyme Q(0) and menadione are found in every cell, including neural cells, and may interact with tau protein to facilitate its assembly into filamentous structures. These tau filaments, assembled in the presence of quinones, have a fibrillar morphology very similar to that of paired helical filaments present in the brains of patients with Alzheimer's disease.

Topics: Amino Acid Motifs; Amino Acid Sequence; Benzoquinones; Cyclic AMP-Dependent Protein Kinases; Humans; Molecular Sequence Data; Naphthoquinones; Neurofibrillary Tangles; Peptide Fragments; Phosphorylation; Polymers; Protein Binding; Protein Processing, Post-Translational; Quinones; Recombinant Proteins; tau Proteins; Tubulin; Ubiquinone; Vitamin K 1; Vitamin K 3

The purpose of this study was to examine the possibility of using Artemia salina as a test organism in the search for compounds having the ability to protect against superoxide-mediated toxicity. The basic procedure for the assay using Artemia salina was performed as described in previous literature, with minor modifications. We found that Artemia salina are extremely sensitive to menadione bisulfite, a compound whose toxicity is probably mediated by intracellular superoxide generation. Desferrioxamine (desferal), a compound with known protective effects, was shown to display dramatic protective activity in our system. We also observed that an inhibitor of endogenous superoxide dismutase (SOD) activity increased the toxicity of menadione toward Artemia salina. In conclusion, this simple, inexpensive, and convenient assay could be a valuable addition to a screening effort in the search for compounds that will be protective against damage by superoxide or other active oxygen species.

Topics: Animals; Artemia; Biological Assay; Deferoxamine; Dimethyl Sulfoxide; Drug Evaluation, Preclinical; Drug Interactions; Hydrogen Peroxide; Naphthoquinones; Paraquat; Potassium Cyanide; Reactive Oxygen Species; Sensitivity and Specificity; Superoxide Dismutase; Superoxides; Ubiquinone; Vitamin K; Vitamin K 3