Chorein deficiency leads to upregulation of gephyrin and GABA(A) receptor

Chorea-acanthocytosis (ChAc) is a hereditary neurodegenerative disorder caused by loss of function mutations in the VPS13A gene encoding chorein. Recently, using a gene-targeting technique to delete exons 60-61, we produced a ChAc-model mouse that corresponds to a human disease mutation. In this study, a comparative microarray analysis of gene expression in the striatum revealed an increased level of gephyrin gene expression in the ChAc-model mice compared with wild type mice. Since gephyrin is known as a GABA(A) receptor-anchoring protein, we compared the protein-level expression and localization of gephyrin and the GABA(A) receptor alpha1 (GABRA1) and gamma2 (GABRG2) subunits. Gephyrin and GABRG2 immunoreactivities in the striatum and hippocampus of the ChAc-model mice were significantly higher than those in the wild types. Our results suggest that chorein functional loss may lead to a compensatory upregulation of gephyrin and GABRG2 in the pathologic condition in ChAc.     

Granuloma-forming activity and antitumor activity of newly isolated mycoloyl glycolipid from Rhodococcus terrae 70012 (Rt. GM-2)

A newly isolated mycoloyl glycolipid (Rt. GM-2) from Rhodococcus terrae 70012 was identified and the granulomagenic and antitumor activities were studied as compared with trehalose-6,6'-dimycolate (cord factor) also from R. terrae (Rt. TDM). The alkaline hydrolysis products of Rt. GM-2 contained trehalose, methyl-alpha-mycolate and a less-polar ester than the usual methyl-alpha-mycolate, possibly beta-keto mycolate (1:1:1, by mol. ratios). On the other hand, analysis of alditol acetate obtained after the mild permethylation, NaBH4 reduction, and acetylation showed the occurrence of 2,3,4-tri-O-methyl-6-O-acetylglucitol. Therefore, the original glycolipid (Rt. GM-2) was identified tentatively as 6-O-alpha-mycoloyl 6'-O-beta-ketomycoloyl trehalose. Intravenous injection of Rt. GM-2 in the form of water-in-oil-in-water emulsion caused prominent granulomas in lungs and spleen of ICR and BALB/c mice. The granulomagenic effects were as strong as those caused by Rt. TDM. The lung and spleen weights reached peaks one week after an injection of Rt. GM-2 in mice and then gradually decreased. Multiple intravenous injections of Rt. GM-2 and Rt. TDM showed antitumor activity against subcutaneously implanted Sarcoma-180, and caused prominent granulomatous changes and growth suppression of mice.     

Metabolic and morphological changes of an oil accumulating trebouxiophycean alga in nitrogen-deficient conditions

Oil-rich algae have promising potential for a next-generation biofuel feedstock. Pseudochoricystis ellipsoidea MBIC 11204, a novel unicellular green algal strain, accumulates a large amount of oil (lipids) in nitrogen-deficient (–N) conditions. Although the oil bodies are easily visualized by lipophilic staining in the cells, little is known about how oil bodies are metabolically synthesized. Clarifying the metabolic profiles in –N conditions is important to understand the physiological mechanisms of lipid accumulations and will be useful to optimize culture conditions efficiently produce industrial oil. Metabolome and lipidome profiles were obtained, respectively, using capillary electrophoresis- and liquid chromatography-mass spectrometry from P. ellipsoidea in both nitrogen-rich (+N; rapid growth) and –N conditions. Relative quantities of more than 300 metabolites were systematically compared between these two conditions. Amino acids in nitrogen assimilation and N-transporting metabolisms were decreased to 1/20 the amount, or less, in –N conditions. In lipid metabolism, the quantities of neutral lipids increased greatly in –N conditions; however, quantities of nearly all the other lipids either decreased or only changed slightly. The morphological changes in +N and –N conditions were also provided by microscopy, and we discuss their relationship to the metabolic changes. This is the first approach to understand the novel algal strain’s metabolism using a combination of wide-scale metabolome analysis and morphological analysis.