Vaccinium ashei leaves extract alleviates insulin resistance via AMPK independent pathway in C2C12 myotube model

Blueberry (Vaccinium ashei) leaf has recently attracted attention as an anti-obesity food component. In this study, we examined the effects of blueberry leaf extract (BLEx) on insulin signaling in C2C12 differentiated myoblasts. The results showed that BLEx promotes the intracellular uptake of 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)amino]?2-deoxy-D-glucose (2-NBDG) and phosphorylation of Akt under insulin stimulation. In addition, pretreatment with BLEx ameliorated TNF-α-nduced insulin resistance with regard to 2-NBDG uptake and Akt phosphorylation. Moreover, BLEx prevented the TNF-α?induced activation of JNK and NF-kB pathways and phosphorylation of IRS-1 at serine residue. BLEx failed to induce phosphorylation of AMPK as well as did not prevent the restoration of 2-NBDG uptake under TNF-α–induced insulin resistance. Overall, skeletal muscle is a putative target for the anti-diabetic effect of BLEx by amelioration of insulin resistance.     

The Arg192 isoform of paraoxonase with low sarin-hydrolyzing activity is dominant in the Japanese

The high-density-lipoprotein-associated enzyme paraoxonase, which has a role in the detoxification of organophosphorus compounds, is known to be polymorphic in humans. The Arg₁₉₂ isoform of paraoxonase hydrolyzes paraoxon more rapidly than the Gln₁₉₂ isoform. However, with respect to the hydrolysis of toxic nerve agents, such as diazoxon, soman, and sarin, the Arg₁₉₂ isoform displays a lower activity than the other isoform. To evaluate the possibility that the genetic polymorphism was involved in the aggravated extent of human injury in the sarin gas poisoning incident in the Tokyo subway in March 1995, we investigated the prevalance of this polymorphism in the Japanese population. We found that the Arg₁₉₂ allele is more common in the Japanese (allele frequency: 0.66) than in people of other races (ranging 0.24–0.31). In the Japanese, 135 out of the 326 subjects (41.4%) investigated were homozygous for the Arg₁₉₂ allele, which shows a very low hydrolysis activity for sarin. Thus, there seems to be a racial difference in vulnerability to toxic nerve agents, such as sarin. The dominance of the Arg₁₉₂ allele in the Japanese population probably worsened the tragedy of March 1995 in the Tokyo subway. Received: 5 April 1997 / Accepted: 10 June 1997     

α2,6-Sialyltransferase Gene Transfection into a Human Glioma Cell Line (U373 MG) Results in Decreased Invasivity

Abstract: Glycosyltransferase gene transfection into cell lines has been an approach used successfully to elucidate the functional role of cell surface glycoconjugates. We have transfected the rat CMP-NeuAc:Galβ1,4GlcNAc α2,6-sialyltransferase (EC 2.4.99.1) gene into a human, tumorigenic, glioma cell line, U373 MG. This transfection led to a marked inhibition of invasivity, alterations in adhesivity to fibronectin and collagen matrices, and inappropriately sialylated α3β1 integrin. Adhesion-mediated protein tyrosine phosphorylation was reduced in the transfectants despite increased expression of focal adhesion kinase, p125^fak. Furthermore, the transfectants showed a distinct cell morphology, an increased number of focal adhesion sites, and different sensitivity to cytochalasin D treatment than control U373 MG cells. These results suggest that inappropriate sialylation of cell surface glycoconjugates, such as integrins, can change focal adhesion as well as adhesion-mediated signal transduction and block glioma cell invasivity in vitro.     

(−)-12-Cytisineacetic acid,a new lupin alkaloid in Euchresta japonica

A new lupin alkaloid, methyl 12-cytisineacetate 1, was isolated from the MeOH extract of Euchresta japonica. Its structure was confirmed by spectrometric data and by direct comparison with a synthetic sample. However, 1 is an artifact product and 12-cytisineacetic acid (2) is assumed to be the principal source of 1.     

Diffusion of nodal signaling activity in the absence of the feedback inhibitor Lefty2.

The role of Lefty2 in left-right patterning was investigated by analysis of mutant mice that lack asymmetric expression of lefty2. These animals exhibited various situs defects including left isomerism. The asymmetric expression of nodal was prolonged and the expression of Pitx2 was upregulated in the mutant embryos. The absence of Lefty2 conferred on Nodal the ability to diffuse over a long distance. Thus, Nodal-responsive genes, including Pitx2, that are normally expressed on the left side were expressed bilaterally in the mutant embryos, even though nodal expression was confined to the left side. These results suggest that Nodal is a long-range signaling molecule but that its range of action is normally limited by the feedback inhibitor Lefty2.     

Evaluation of the general suitability of the rat for the micronucleus assay: the effect of cyclophosphamide in 14 strains.

To evaluate the general suitability of the rat for the micronucleus assay, we conducted the assay in males of 14 different strains, 13 inbred (ACI, BN, BUF, COP, DRH, F344, IS, LEW, RCS, SHR, WAG, WKYO, WTC) and 1 outbred (SD), using cyclophosphamide as the test chemical. Cyclophosphamide at 0 (vehicle), 5, 10, or 20mg/kg per day was administered orally twice, 24h apart, to five rats per dosage group. Bone marrow and peripheral blood were collected 24h after the second treatment.All 14 strains showed a positive response to cyclophosphamide, with slight differences in sensitivity. We concluded that the rat is suitable for the micronucleus assay regardless of strain.