HIF-1␣ is a hypoxia-inducible protein that regulates many cell and molecular processes, including those involved in angiogenesis and

Myelin proteolipid protein (PLP) contains thioester-bound, long-chain fatty acids which are known to in¯uence the structure of the molecule. To gain further insights into the role of this post-translational modi®cation, we studied the effect that chemical deacylation of PLP had on the morphology of myelin and on the protein's ability to mediate the clustering of lipid vesicles. Incubation of rat optic nerves in isoosmotic solutions containing 100 mM hydroxylamine (HA) pH 7.4 led to deacylation of PLP and decompaction of myelin lamellae at the level of the intraperiod line. Incubation of nerves with milder nucleophilic agents (Tris and methylamine) or diluted HA, conditions that do not remove protein-bound fatty acids, caused no alterations in myelin structure. Other possible effects of HA which could have affected myelin compaction indirectly were ruled out. Incubation of optic nerves with 50 mM dithioerythritol (DTE) also led to the splitting of the myelin intraperiod line and this change again coincided with the removal of fatty acids. In addition, the apparently compacted CNS myelin in the PLP-less myelin-de®cient rat, like that in tissue containing deacylated PLP, was readily decompacted upon incubation in isoosmotic buffers, suggesting that the function of PLP as a stabilizer of the interlamellar attachment is, at least in part, mediated by fatty acylation. Furthermore, in contrast to the native protein, PLP deacylated with either HA or DTE failed to induce the clustering of phosphatidylcholine/cholesterol vesicles in vitro. This phenomenon is not due to side-effects of the deacylation procedure since, upon partial repalmitoylation, the protein recovered most of its original vesicle-clustering activity. Collectively, these ®ndings suggest that palmitoylation, by in¯uencing the adhesive properties of PLP, is important for stabilizing the multilamellar structure of myelin.

Purpose of Review The use of erythropoiesis stimulating agents (ESAs) such as erythropoietin (Epo) and Darbepoetin (Darbe) in preterm and term infants has been studied for over 20 years. Recent investigations have explored potential neuroprotective effects of ESAs. We review recent clinical trials and experimental animal models that provide evidence in support of using ESA to improve neurodevelopmental outcomes in term and preterm infants. Recent Findings Continued work using animal models have confirmed neuroprotective properties of ESAs, including promotion of oligodendrocyte development in the face of neuronal injury. Clinical studies in term and preterm infants have reported neuroprotective effects following ESA administration, and improved neurodevelopmental outcomes have been reported in studies of preterm infants. Summary ESAs show great promise in preventing and treating brain injury in term and preterm infants.

Myelin proteolipid protein (PLP) is modified after translation by the attachment of long-chain fatty acids to several cysteine residues. In this study, the amount and pattern of fatty acids covalently bound to rat PLP were determined during brain development and in myelin subfractions. For this purpose, PLP was isolated by gel-filtration chromatography in organic solvents, subjected to alkaline methanolysis, and the released fatty acid methyl esters were analyzed by gas-liquid chromatography. At all ages examined, PLP had the same amount of covalently-bound fatty acids (3-4% w/w) and palmitate, oleate and stearate were always the major acyl chains. In contrast to myelin lipids, the fatty acid composition of PLP showed only minor changes between 15-days and 90-days of age. The amount and pattern of fatty acids bound to PLP prepared from three myelin subfractions were also indistinguishable. The conservation of a characteristic PLP-fatty acid make-up during brain development and in various myelin compartments suggests that this post-translational modification is essential for the normal functioning of the protein.