phosphorus-radioisotopes and Huntington-Disease

CAG repeats are present in numerous human transcripts but neither their structures nor physiological functions have been satisfactorily recognized. The expanded CAG repeats are present in transcripts from several mutant genes associated with hereditary neurodegenerative diseases but their contribution to pathogenesis has not been documented convincingly. Here, we show that the structures formed by the repeats and their natural flanking sequences in the spinocerebellar ataxia (SCA) type 3 and type 6, and dentatorubral-palidoluysian atrophy (DRPLA) transcripts have different molecular architectures which may have functional meaning. We provide evidence that the hairpin structure formed by CAG repeats in mRNA fragments is preserved in full-length mRNA. We also demonstrate that the single-nucleotide polymorphism (SNP) that is located immediately adjacent (3') to the repeats of the SCA3 transcript modulates the structures formed by these sequences, and may have functional significance, as only one of its variants is selected in human evolution.

Topics: Ataxin-3; Calcium Channels; Electrophoresis, Polyacrylamide Gel; Genetic Variation; Humans; Huntington Disease; MicroRNAs; Models, Genetic; Models, Molecular; Mutation; Myoclonic Epilepsies, Progressive; Nerve Tissue Proteins; Nuclear Proteins; Phosphorus Radioisotopes; Polymorphism, Single Nucleotide; Repressor Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Spinocerebellar Ataxias; Transcription, Genetic; Trinucleotide Repeat Expansion; Trinucleotide Repeats

Topics: Adult; Brain; Humans; Huntington Disease; Magnetic Resonance Spectroscopy; Male; Phosphorus Radioisotopes; Schizophrenia

The hypothesis that there is impaired endogenous synthesis of glucosamine 6-phosphate in Huntington's-chorea fibroblasts was tested by double labelling matched pairs of fibroblasts in culture with carrier-free H3 32PO4 and [U-14C]glucosamine. The [32P]UDP-N-acetyl[14C]glucosamine and [14C]glucosamine 6-[32P]phosphate of the cellular soluble fraction was isolated by charcoal column and paper chromatography. There is no quantitative difference in 32P but a significant difference in 14C in these two sugars in a ratio of approx. 1.5 for Huntington's-chorea fibroblasts compared with normal fibroblasts.

Topics: Carbon Radioisotopes; Cell Line; Fibroblasts; Glucosamine; Hexosamines; Humans; Huntington Disease; Nucleotides; Phosphorus Radioisotopes; Skin; Uridine Diphosphate N-Acetylglucosamine; Uridine Diphosphate Sugars

Topics: Acetylcholine; Animals; Brain Chemistry; Choline; Chromatography, Gas; Corpus Striatum; Deanol; Disease Models, Animal; Ethanolamines; Huntington Disease; Kainic Acid; Male; Phosphorus Radioisotopes; Pyrrolidines; Rats