Peritoneal fluids from patients with certain gynecologic tumor contain elevated levels of bioactive lysophospholipase D activity

Levels of lysophosphatidic acid (LPA), an important phospholipid mediator, in serum and ascitic fluid from ovarian cancer patients were shown to be higher than those from healthy women and from patients with other type of cancer, respectively. Although LPA in human serum seems mainly to be generated by lysophospholipase D (lysoPLD), the source and pathway for LPA in the ascitic fluid remain still obscure. In this study, we examined whether lysoPLD activity producing bioactive LPA in human peritoneal fluid was significantly elevated under pathological statuses. Lysophospholipase D activity in human peritoneal fluids was measured by quantifying choline released from exogenous lysophosphatidylcholine on their incubation at 37 degrees C. We also compared the activity of lysoPLD in sera from patients with different gynecologic diseases. We found relatively high lysoPLD activity in peritoneal fluids from patients with ovarian cancer, dermoid cyst or mucinous cystadenoma, whereas there were no significant differences in the serum lysoPLD activity among clinical groups and healthy subjects. The lysoPLD in the peritoneal fluid was found to have similar substrate specificity and metal ion requirement to those of serum lysoPLD, that has been identified as autotaxin, a tumor cell-motility stimulating protein. Our results suggest that increased lysoPLD activity in peritoneal fluid from patients with certain gynecologic tumors might be relevant to its potential of tumor progression.     

Antifungal nitro compounds from skunk cabbage (Lysichitum americanum) leaves treated with cupric chloride

Two nitro compounds, 2-(4-methoxyphenyl)-1-nitroethane named as lysichitalexin and 2-(4-hydroxyphenyl)-1-nitroethane were isolated as stress metabolites from the leaves of Lysichitum americanum Hultén and St. John treated with cupric chloride. Their structures were determined by spectroscopic methods and chemical reactions. The former compound showed antifungal activities against Fusarium oxysporum and Cladosporium herbarum. Both compounds were isolated for the first time from this species and the former was isolated from natural sources for the first time. This is the first report on stress metabolites from a member of the Araceae.     

Decreased Amyloid-β Pathologies by Intracerebral Loading of Glycosphingolipid-enriched Exosomes in Alzheimer Model Mice

Elevated levels of amyloid-β peptide (Aβ) in the human brain are linked to the pathogenesis of Alzheimer disease. Recent in vitro studies have demonstrated that extracellular Aβ can bind to exosomes, which are cell-secreted nanovesicles with lipid membranes that are known to transport their cargos intercellularly. Such findings suggest that the exosomes are involved in Aβ metabolism in brain. Here, we found that neuroblastoma-derived exosomes exogenously injected into mouse brains trapped Aβ and with the associated Aβ were internalized into brain-resident phagocyte microglia. Accordingly, continuous intracerebral administration of the exosomes into amyloid-β precursor protein transgenic mice resulted in marked reductions in Aβ levels, amyloid depositions, and Aβ-mediated synaptotoxicity in the hippocampus. In addition, we determined that glycosphingolipids (GSLs), a group of membrane glycolipids, are highly abundant in the exosomes, and the enriched glycans of the GSLs are essential for Aβ binding and assembly on the exosomes both in vitro and in vivo. Our data demonstrate that intracerebrally administered exosomes can act as potent scavengers for Aβ by carrying it on the exosome surface GSLs and suggest a role of exosomes in Aβ clearance in the central nervous system. Improving Aβ clearance by exosome administration would provide a novel therapeutic intervention for Alzheimer disease.     

Body composition and physical fitness of female volleyball and basketball players of the Japan inter-high school championship teams

This study evaluated the body composition (underwater weighing) and cardiorespiratory function (VO(2)max and O(2)debt max measured by the treadmill exercise test) in 12 members of the women's volleyball team (mean age 17.4 years) and 11 members of the women's basketball team (mean age 17.6 years) that won the championship in the Japan Inter-high School Meeting. We also examined differences in the physical abilities between the members of the top teams of different events. The following results were obtained. (1) The mean values of the height and body weight were 168.7+/-5.89 cm and 59.7+/-5.73 kg in the volleyball players and 166.5+/-7.87 cm and 58.8+/-6.85 kg in the basketball players. (2) The mean %Fat was 18.4+/-3.29% in the volleyball players and 15.7+/-5.05% in the basketball players, and was similar to the reported values in elite adult players. (3) The mean VO(2)max was 2.78+/-0.32 L x min(-1) (46.5+/-2.90 ml x kg(-1) x min(-1)) in the volleyball players and 3.32+/-0.31 L x min(-1) (56.7+/-4.17 ml x kg(-1) x min(-1)) in the basketball players, and was similar to the reported values in elite adult players. (4) The mean O(2)debt max was 6.18+/-1.15 L (103.2+/-12.40 ml x kg(-1)) in the volleyball players and 7.92+/-1.80 L (134.3+/-23.24 ml x kg(-1)) in the basketball players. These values were 2.6 times and 3.3 times as high as the average values in high school students in general. (5) No significant difference was observed in any measured item of the physique, skinfold thickness, or body composition between the volleyball players and basketball players. (6) The VO(2)max and O(2)debt max were 22% and 28% higher in the basketball players than in the volleyball players.From these results, the female volleyball players and basketball players evaluated in this study had the physical abilities needed to win the championship in the Japan Inter-high School Meets, i.e. a large FFM and excellent aerobic and anaerobic work capacities. Also, basketball appears to require higher aerobic and anaerobic work capacities than volleyball.     

Isolation of stable (alphabeta)4-Tetraprotomer from Na+/K+-ATPase solubilized in the presence of short-chain fatty acids

Previously, it was demonstrated that acetate anions increase the higher oligomer (H), consuming (alphabeta) 2-diprotomer (D) and alphabeta-protomer (P) of solubilized dog kidney Na (+)/K (+)-ATPase [ Kobayashi, T. et al. (2007) J. Biochem. 142, 157-173 ]. Presently, short-chain fatty acids, such as propionate (Prop) and butyrate, have been substituted effectively for acetate. The molecular weight of 6.01 x 10 (5) for H and quantitative Na (+)/K (+)-dependent interconversion among H, D, and P showed that H was an (alphabeta) 4-tetraprotomer (T). T was optimally isolated from the enzyme solubilized in aqueous 40 mM K (+)Prop at pH 5.6 by gel chromatography performed at 0 degrees C with elution buffer containing synthetic dioleoyl phosphatidylserine (PS). K 0.5 values of K (+)-congeners constituting K (+)Prop for the maximal amount of T were NH 4 (+) > Rb (+) congruent with K (+) > Tl (+), while Na (+) had no effect. The oligomers of T, D, and P were simultaneously assayed for ATPase upon elution from the gel column, resulting in a specific activity ratio of 1:2:2. The activity of the chromatographically isolated T increased with an increasing dioleoyl PS, giving a saturated activity of 2.38 units/mg at pH 5.6 and 25 degrees C, and the active enzyme chromatography of T showed 34% dissociation into D by exposing it at 25 degrees C. On the basis of these data, the specific ATPase activities of T, D, and P were concluded to be 32, 65, and 65 units/mg, respectively, under the conventionally optimal conditions of pH 7.3 and 37 degrees C, suggesting an equivalence to a fully active enzyme for D and P but half activity for T. The physiological significance of the stable form of T remains to be investigated.     

Autocrine/Paracrine secretion of IL-6 family cytokines causes angiotensin II-induced delayed STAT3 activation

We recently reported that angiotensin II (AngII) biphasically activates the JAK/STAT pathway and induces delayed phosphorylation of STAT3 in the late stage (120 min) in cardiomyocytes. This study was designed to determine the mechanism of delayed phosphorylation of STAT3. Conditioned medium prepared from AngII-stimulated cardiomyocytes could reproduce the tyrosine phosphorylation of STAT3 at 5 min. This delayed phosphorylation was almost completely inhibited by anti-gp130 blocking antibody RX435, but not by TAK044 (ET-A/B-R antagonist), prazosin, or propranolol. AngII induced phosphorylation of gp130 in the late stage, which was temporally in parallel with the delayed phosphorylation of STAT3. AngII augmented IL-6, CT-1, and LIF mRNA expression at 30-60 min, but not CNTF expression. AngII increased IL-6 protein levels by 3-fold in the conditioned media at 2 h compared with the control. These findings indicated that AngII-induced delayed activation of STAT3 is caused by autocrine/paracrine secreted IL-6 family cytokines.     

Maturation-related variations in prostaglandin and fatty acid content of ovary in the kuruma prawn (Marsupenaeus japonicus)

Total lipid, fatty acids and prostaglandins (PGF(2 alpha) and PGE(2)) in the ovary of kuruma prawns (Marsupenaeus japonicus) were measured during ovarian development. The level of ovarian total lipid increased with an increase in the gonad-somatic index (GSI). No significant difference was found in fatty acid composition among different stages of ovarian development. However, the content of arachidonic acid (precursor of PG(2)), but not eicosapentanoic acid (precursor of PG(3)), was significantly lower at stages I and II than at stage V (P<0.01). When ovarian PGF(2 alpha) and PGE(2) levels were plotted against GSI, no correlation was found in either PG. However, in terms of ovarian developmental stages, the level of ovarian PGs was high (approx. 20 pg/mg) at stage I, followed by marked decreases at stages IV and V (PGF(2 alpha), P<0.01) and stage IV (PGE(2), P<0.01). These results suggest that ovarian PGs and arachidonic acid are deeply involved in ovarian maturation in kuruma prawns.