RNA METABOLISM IN THE GOLDFISH RETINA DURING OPTIC NERVE REGENERATION 1, 2

In goldfish, regeneration of the optic nerve following axotomy is accompanied by changes in retinal RNA metabolism. Approximately 4 days after unilateral optic nerve crush, there is an increased uptake of 3 H-labeled precursors of RNA into cells of the retina as well as an increase in labeling of total retinal RNA following incubation for 3–4 h in vitro. Subfractionation indicates that the resultant labeled free ribosomai RNA has a much higher specific activity than that from membrane-bound ribosomes in post-crush, as compared to normal retinas. Total retinal RNA content also increases, reaching a peak value about 8 days after axotomy, coincident with the time of observed maximum labeling of ribosomal RNA. No change in the total protein or DNA content of the retina is detected during this period as a result of the optic nerve crush. Saturating amounts of uridine or adenosine in the medium eliminate the general effects of enhanced uptake of the precursors on RNA labeling. Elevated labeling of poly(A)-containing RNA in retinal cytoplasm is nevertheless detected 10–14 days after optic nerve crush with no change in the labeling of the polyadenylate segment. A decrease in the labeling of poly(A)-containing nuclear RNA, from a significantly greater amount than that of normal retinas to a significantly lower one, occurs during the period of observed increased labeling of cytoplasmic poly(A)-containing RNA. The results indicate that in addition to changes in RNA precursor metabolism, optic nerve regeneration is characterized by alterations in the labeling of free and membrane-bound retinal ribosomes as well as in the post-transcriptional processing of messenger RNA.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66175/1/j.1471-4159.1978.tb12462.x.pd

Cascade oxime formation, cyclization to a nitrone, and intermolecular dipolar cycloaddition.

Simple haloaldehydes, including enolisable aldehydes, were found to be suitable for the formation of cyclic products by cascade (domino) condensation, cyclisation, dipolar cycloaddition chemistry. This multi-component reaction approach to heterocyclic compounds was explored by using hydroxylamine, a selection of aldehydes, and a selection of activated dipolarophiles. Initial condensation gives intermediate oximes that undergo cyclisation with displacement of halide to give intermediate nitrones; these nitrones undergo in situ intermolecular dipolar cycloaddition reactions to give isoxazolidines. The cycloadducts from using dimethyl fumarate were treated with zinc/acetic acid to give lactam products and this provides an easy way to prepare pyrrolizinones, indolizinones, and pyrrolo[2,1-a]isoquinolinones. The chemistry is illustrated with a very short synthesis of the pyrrolizidine alkaloid macronecine and a formal synthesis of petasinecine

Uridine Metabolism in the Goldfish Retina During Optic Nerve Regeneration: Whole Retina Studies

Accumulation of radioactivity from [ 3 H]uridine in incubations of whole goldfish retinas is increased in the ipsilateral retina during a period of regeneration that follows unilateral optic nerve crush. Brief incubations to investigate the nature of enhanced labeling of the acid-soluble fraction showed a peak uptake 4 days following crush, with a gradual decrease to control levels by 21 days following crush. That nucleoside uptake may not mediate the effect is supported by the observation that the rate of uptake of 5′-deoxyadenosine, a nonmetabolizable nucleoside analog, is the same in post-crush (PC) and normal (N) retinal incubations. Following brief incubations of PC and N retinas with [ 3 H]uridine, there is enhanced labeling in PC retinas relative to N retinas of recovered UMP, UDP, UTP, and uridine nucleotide sugars, whereas recovery of labeled uridine itself is slightly decreased. The results suggest that the increased accumulation of radioactivity in PC retinas following incubation with uridine reflects an increase in the activities of retinal uridine kinase and uridine nucleotide kinases.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65630/1/j.1471-4159.1981.tb01713.x.pd