Inactivation of spermidine N1-acetyltransferase with alkaline phosphatase

AbstractSpermidine N1-acetyltransferase in an extract from phytohemagglutinin-stimulated bovine lymphocytes was inactivated by preincubation with alkaline phosphatase. Inactivation of the acetylase with the phosphatase was totally inhibited by addition of pyrophosphate. These results suggest that spermidine N1-acetyltransferase, the rate-limiting enzyme in the biodegradative pathway of polyamines, is inactivated by dephosphorylation. A similar effect of alkaline phosphatase on the acetylase in an extract from Escherichia coli was also observed. The acetylase has a rapid rate of turnover and the rapid loss of the enzyme activity may be to some extent regulated by the covalent modification

Electron microscopic and infrared spectral studies on the structure of alumina phases

Alumina produced by oxidation of aluminum in air was studied by infrared spectroscopy and electron microscopy. Infrared spectra of both alumina particles and alumina film oxidized in air showed an absorption peak at 10.8μm, though that of γ-Al_2O_3 particles showed a broad 13μm peak. On the basis of the infrared spectra and electron diffraction pattern, it was concluded that alumina produced by the oxidation of aluminum in air is η-Al_2O_3. The phase transition from η-phase to γ-phase and to α-phase took place at 900℃ and 1100℃, respectively. The relationships between infrared spectra and crystal structure of some alumina phases are discussed

The Fungal Metabolite (+)-Terrein Abrogates Ovariectomy-Induced Bone Loss and Receptor Activator of Nuclear Factor-kappa B Ligand-Induced Osteoclastogenesis by Suppressing Protein Kinase-C alpha/beta II Phosphorylation

Osteoporosis is a common disease characterized by a systemic impairment of bone mass and microarchitecture that results in fragility fractures. Severe bone loss due to osteoporosis triggers pathological fractures and consequently decreases the daily life activity and quality of life. Therefore, prevention of osteoporosis has become an important issue to be addressed. We have reported that the fungal secondary metabolite (+)-terrein (TER), a natural compound derived from Aspergillus terreus, has shown receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast differentiation by suppressing nuclear factor of activated T-cell 1 (NFATc1) expression, a master regulator of osteoclastogenesis. TER has been shown to possess extensive biological and pharmacological benefits; however, its effects on bone metabolism remain unclear. In this study, we investigated the effects of TER on the femoral bone metabolism using a mouse-ovariectomized osteoporosis model (OVX mice) and then on RANKL signal transduction using mouse bone marrow macrophages (mBMMs). In vivo administration of TER significantly improved bone density, bone mass, and trabecular number in OVX mice (p < 0.01). In addition, TER suppressed TRAP and cathepsin-K expression in the tissue sections of OVX mice (p < 0.01). In an in vitro study, TER suppressed RANKL-induced phosphorylation of PKC alpha/beta II, which is involved in the expression of NFATc1 (p < 0.05). The PKC inhibitor, GF109203X, also inhibited RANKL-induced osteoclastogenesis in mBMMs as well as TER. In addition, TER suppressed the expression of osteoclastogenesis-related genes, such as Ocstamp, Dcstamp, Calcr, Atp6v0d2, Oscar, and Itgb3 (p < 0.01). These results provide promising evidence for the potential therapeutic application of TER as a novel treatment compound against osteoporosis

Anti-malarial activity of leaf-extract of hydrangea macrophylla, a common Japanese plant.

To find a new anti-malarial medicine derived from natural resources, we examined the leaves of 13 common Japanese plants in vitro. Among them, a leaf-extract of Hydrangea macrophylla, a common Japanese flower, inhibited the parasitic growth of Plasmodium falciparum. The IC50 of Hydrangea macrophylla leaf extract to Plasmodium falciparum was 0.18 microg/ml. The IC50 to NIH 3T3-3 cells, from a normal mouse cell line, was 7.2 microg/ml. Thus, selective toxicity was 40. For the in vivo test, we inoculated Plasmodium berghei, a rodent malaria parasite, to ddY mice and administered the leaf-extract of Hydrangea macrophylla (3.6 mg/0.2 ml) orally 3 times a day for 3 days. Malaria parasites did not appear in the blood of in the treated mice, but they did appear in the control group on day 3 or 4 after inoculation with the parasites. When leaf extract was administered to 5 mice 2 times a day for 3 days, malaria parasites did not appear in 4 of the mice but did appear in 1 mouse. In addition, the leaf-extract was administered orally 3 times a day for 3 days to Plasmodium berghei infected mice with a parasitemia of 2.7%. In the latter group, malaria parasites disappeared on day 3 after initiating the treatment, but they appeared again after day 5 or 6. Although we could not cure the mice entirely, we confirmed that the Hydrangea macrophylla leaf extract did contain an anti-malarial substance that can be administered orally.</p

Thymidine triphosphate dephosphorylating activity in regenerating rat liver

AbstractThe enzyme activity of dephosphorylation of thymidine triphosphate was found in microsomal fraction of rat liver. The enzyme activity decreased at the time when [3H]thymidine incorporation into DNA of regenerating liver increased. When the [3H]thymidine incorporation was suppressed by 1,3-diaminopropane, the enzyme activity remained elevated. These results suggest that the enzyme activity appears to be closely linked to DNA synthesis

Prostaglandin D2 Induces Ca2+ Sensitization of Contraction without Affecting Cytosolic Ca2+ Level in Bronchial Smooth Muscle

Prostaglandin D2 (PGD2) is one of the key lipid mediators of allergic airway inflammation, including bronchial asthma. However, the role of PGD2 in the pathogenesis of asthma is not fully understood. In the present study, the effect of PGD2 on smooth muscle contractility of the airways was determined to elucidate its role in the development of airway hyperresponsiveness (AHR). In isolated bronchial smooth muscles (BSMs) of naive mice, application of PGD2 (10&minus;9&ndash;10&minus;5 M) had no effect on the baseline tension. However, when the tissues were precontracted partially with 30 mM K+ (in the presence of 10&minus;6 M atropine), PGD2 markedly augmented the contraction induced by the high K+ depolarization. The PGD2-induced augmentation of contraction was significantly inhibited both by 10&minus;6 M laropiprant (a selective DP1 antagonist) and 10&minus;7 M Y-27632 (a Rho-kinase inhibitor), indicating that a DP1 receptor-mediated activation of Rho-kinase is involved in the PGD2-induced BSM hyperresponsiveness. Indeed, the GTP-RhoA pull-down assay revealed an increase in active form of RhoA in the PGD2-treated mouse BSMs. On the other hand, in the high K+-depolarized cultured human BSM cells, PGD2 caused no further increase in cytosolic Ca2+ concentration. These findings suggest that PGD2 causes RhoA/Rho-kinase-mediated Ca2+ sensitization of BSM contraction to augment its contractility. Increased PGD2 level in the airways might be a cause of the AHR in asthma