Highly potent and specific inhibitors of human renin

We designed aldehyde derivatives of small peptides representing the C-terminal portion of angiotensin I sequence as an inhibitor of human renin. Among compounds that we synthesized, benzyloxycarbonyl (Z)-Phe-His-Leucinal (compound V), Z-Pro-Phe-His-Leucinal (Compound IV) and Z-[3-(1'-naphthyl)Ala]-His-Leucinal (compound VII) markedly inhibited human renin (IC50, 7.5 X 10(-7), 3.2 X 10(-7) and 8.0 X 10(-8) mol/l, respectively). Compound VII was shown to be noncompetitive (Ki = 2.4 X 10(-7) mol/l). It did not inhibit either cathepsin D or pepsin. Compound V had slight or no inhibitory effect at the concentration of 10(-5) mol/l on six animal renins except for monkey and rabbit renins. Results obtained show that these aldehyde compounds are highly selective and species specific inhibitors for human and monkey renins.     

Effects of Net and Local Charges on the Interaction between Chemically-Modified Horse Heart Cytochrome c and P700 in Photosystem 1-Enriched Subchloroplast Particles

Effects of salt and pH on the re-reduction of P700 by chemically-modifiedhorse heart cytochrome c after a flash illumination were examinedin Triton-treated P700- enriched subchloroplast particles (TSF-1particles). At low salt concentrations net charges on the membrane surfaceand native, guanidinated or succinylated cytochrome c were majorfactors that determined the reaction rates, as in the reactionbetween plastocyanin and P700 [Tamura et al. (1981) Plant &Cell Physiol. 22: 603]. The reaction rates also depended onreactant-specific factors, particularly the localized distributionof charges on macromolecules and their interaction over shortdistances, as well as on long-range Coulombic interaction. Theeffect of this type became clearer at high salt concentrations. (Received October 7, 1982; Accepted December 20, 1982)     

Blue light induced inhibition of seed germination: The necessity of the fruit coats for the blue light response

The seeds (achenes) of Laportea bulbifera require a chilling to break their dormancy and are negatively photoblastic. Their germination is inhibited by both continuous blue light and continuous or prolonged far-red radiation. The germination of de-coated seeds, prepared by removing the fruit coats, however, was strongly inhibited by continuous far-red, but not by continuous blue light. Photoreversible germination by a brief irradiation with red light occurred when the chilled seeds were exposed to prolonged far-red light. These results suggest that far-red light may regulate the germination of L. bulbifera seeds through the phytochrome system which exists in the regions other than fruit coats and that the blue light reaction may be governed by other photoreceptor system(s).     

An inducible lactone hydrolase yielding 2,5-diphenyl-3-hydroxy-4-oxo-2-hexendioic acid from pulvinic acid

The metabolism of vulpinic acid by an unclassified soil micro-organism was studied. A new compound, 2,5-diphenyl-3-hydroxy-4-oxo-2-hexendioic acid (DHOHA) was isolated from the reaction mixture of a cell-free preparation and pulvinic acid. The existence of a hydrolase which catalyses the conversion of vulpinic acid to pulvinic acid was detected in cell-free preparation, and an inducible lactone hydrolase capable of converting pulvinic acid to DHOHA was purified 130-fold and characterized. This enzyme had a MW of ca 34 000, a K_m for pulvinic acid at pH optimum (pH 7.0) less than 10 ^{? 6} M, pI = 5.0, and was inhibited by p-chloromercuriphenylsulfonate and diethylpyrocarbonate. The enzyme was highly specific for pulvinic acid. The initial degradative steps proposed for this organism are vulpinic acid → pulvinic acid → DHOHA.     

Histochemical studies on the morphology of the Golgi apparatus in the neurons of supraoptic and paraventricular nuclei of the normal and dehydrated rabbit (application of the thiamine pyrophosphatase method)

Summary Detailed histochemical studies have been conducted on the morphology of the Golgi apparatus by applying the thiamine pyrophosphatase technique (Novikoff and Goldfisher, 1961) to the neurons of supraoptic and paraventricular nuclei of normal and dehydrated rabbits. The neurons in both nuclei were classified into five categories on the basis of the morphology of the Golgi apparatus. The number of cells in individual categories were counted to evaluate the percentage of each category in the whole nucleus.Neurons have many vesicles which show the tendency to form clusters. Such clusters are present also in the basal bodies. The Golgi apparatus is localized near one side of the nucleus in many neurons. The neurons indicate phasic activity of resting, anabolic and catabolic stages under normal conditions.During dehydration, the Golgi apparatus went through the three stages of network formation, the increase of the budding-off process and later on disintegration. The supraoptic nucleus reacted to the TPPase test more severely than the paraventricular nucleus, whereas the former went through the stages more slowly than the latter. The paraventricular nucleus also revealed sensitivity to osmotic stress.     

Histochemical studies on the distribution of some enzymes of the glycolytic pathways in the olfactory bulb of the squirrel monkey (Saimiri sciureus)

Summary Detailed histochemical studies on the distribution of glycolytic enzymes have been made in the olfactory bulb of the Squirrel Monkey. The olfactory glomeruli, mitral cells, tufted cells, glial cells and nerve fibers are well equipped with the enzymes of the glycolytic pathways. Granule cells do not have the ability to synthesize or breakdown glycogen, but they have the Embden-Meyerhof-Parnas pathway and the Warburg-Dickens pathway. The synapses of the olfactory glomeruli may have the ability to break-down glycogen for an energy source. Small glial cells found in the olfactory glomeruli may be a special type of oligodendrocyte. Glial cells found abundantly in and around the olfactory glomeruli may be energy donators to the synapses of the olfactory glomeruli. It is suggested that oligodendrocytes and astrocytes of the olfactory bulb may have different branching enzymes.Visiting scientist from Anatomy Department, Tokyo Medical and Dental University, Tokyo, Japan. T. R. Shanthaveerappa in previous publications.     

Tumor cytotoxicity of human monocyte membrane-bound interleukin-1α induced by synergistic actions of interferon-γ and synthetic acyltripeptide,FK-565

Summary Human blood monocytes were isolated by counter-flow centrifugal elutriation from healthy donors and these noncytotoxic monocytes were rendered tumoricidal to allogeneic melanoma (A375) cells by activation with a synthetic acyltripeptide (FK-565), as assessed by measuring release of [¹²⁵I]iododeoxyuridine in 72 h. When monocytes were treated with FK-565 for 16 h, and then fixed with paraformaldehyde, they showed cytotoxicity to A375 melanoma cells. The fixed-monocyte-mediated cytotoxicity to A375 cells was induced by the synergistic actions of FK-565 and recombinant interferon- (rIFN-), but not other cytokines [rIFN-A, rIFN-, tumor necrosis factor (TNF), interleukin (IL)-2, -3 and -6]. For synergistic activation of monocytes with induction of a membrane-associated antitumor monokine, the monocytes had to be incubated first with rIFN- and then with FK-565. FK-565 also acted synergistically with rIFN- to stimulate monocytes to produce membrane-associated IL-1 activity, which induced C3H/HeJ thymocyte blastogenesis in response to phytohemagglutinin P. The tumoricidal and thymocytestimulating activities of the fixed monocytes were almost completely inhibited by a specific anti-(IL-1) antiserum, but not by a specific anti-(IL-1) antiserum or monoclonal anti-TNF antibody. These results suggest that membrane-associated IL-1 of human blood monocytes can be induced by two activation signals (rIFN- then FK-565) at their suboptimal concentrations.Abbreviations IL interleukin - IFN interferon - TNF tumor necrosis factor     

The Role in Ozone Phytotoxicity of the Evolution of Ethylene upon Induction of 1-Aminocydopropane-1-carboxylic Acid Synthase by Ozone Fumigation in Tomato Plants

The rate of evolution of ethylene by tomato plants was rapidlyincreased by O₃ fumigation. The time course of the increasein 1-aminocyclopropane-1-carboxylic acid (ACC) synthase activitywas the same as that in the rate of evolution of ethylene, suggestingthat ACC synthase activity might be a rate-limiting step inthe evolution of ethylene that is caused by O₃ fumigation. Therate of the O₃-induced evolution of ethylene was increased bythe application of ACC to tomato plants, suggesting the involvementof ACC oxidase in the O₃-induced evolution of ethylene. Treatmentof plants with tiron inhibited the evolution of ethane, butnot of ethylene. These results indicated that evolution of ethylenein O₃-treated tomato plants might result from enzymatic reactionscatalyzed by both ACC synthase and ACC oxidase, but not fromstimulation by O₃ of the peroxidation of lipids mediated byfree radicals. Pretreatment of leaves with aminoethoxyvinylglycine (AVG), aninhibitor of ACC synthase, significantly inhibited the evolutionof ethylene that was induced by O₃ and concomitantly reducedthe extent of O₃-induced visible damage to leaves. Treatmentwith 2,5-norbonadiene, an inhibitor of the action of ethylene,strongly reduced the extent of visible damage caused by O₃,even though it did not suppress the evloution of ethylene. Theseresults indicate that ethylene acts on certain metabolic processesto cause visible damage. (Received September 7, 1995; Accepted December 18, 1995)