Mechanism of action of the antiplatelet peptide, arietin, from Bitis arietans venom

Arietin, an Arg-Gly-Asp containing peptide from venom of Bitis arietans, inhibited aggregation of platelets stimulated by a variety of agonists with a similar IC50, 1.3-2.7.10(-7) M. It blocked aggregation through the interference of fibrinogen binding to fibrinogen receptors on platelet surface. In this paper, we further demonstrated that arietin had no significant effect on the intracellular mobilization of Ca2+ in Quin2-AM-loaded platelets stimulated by thrombin. It inhibited 125I-fibrinogen binding to ADP-stimulated platelets in a competitive manner (IC50, 1.1.10(-7) M). 125I-arietin bound to unstimulated, ADP-stimulated and elastase-treated platelets in a saturable manner and its Kd values were estimated to be 3.4.10(-7), 3.4.10(-8) and 6.5.10(-8) M, respectively, while the corresponding binding sites were 46,904, 48,958 and 34,817 per platelet, respectively. Arg-Gly-Asp-Ser (RGDS) inhibited 125I-arietin binding to ADP-stimulated platelets in a competitive manner. RGD-containing peptides, including trigramin and rhodostomin, EDTA and monoclonal antibody, 7E3, raised against glycoprotein IIb-IIIa complex, inhibited 125I-arietin binding to ADP-stimulated platelets, indicating that the binding sites of arietin appear to be located at or near glycoprotein IIb-IIIa complex. In conclusion, arietin and other RGD-containing trigramin-like peptides preferentially bind to the fibrinogen receptors associated with glycoprotein IIb-IIIa complex of the activated platelets, thus leading to the blockade of fibrinogen binding to its receptors and subsequent aggregation. The presence of RGD of arietin is essential for the expression of its biological activity. Its binding sites are overlapped with those of trigramin, rhodostomin and the monoclonal antibody, 7E3.     

Molecular dynamics computations and solid state nuclear magnetic resonance of the gramicidin cation channel.

This paper reports on a coupled approach to determining the structure of the gramicidin A ion channel, utilizing solid state nuclear magnetic resonance (NMR) of isotopically labeled gramicidin channels aligned parallel to the magnetic field direction, and molecular dynamics (MD). MD computations using an idealized right-handed beta-helix as a starting point produce a refined molecular structure that is in excellent agreement with atomic resolution solid state NMR data. The data provided by NMR and MD are complementary to each other. When applied in a coordinated manner they provide a powerful approach to structure determination in molecular systems not readily amenable to x-ray diffraction.     

Salivary peroxidase,Pm, and Ph protein polymorphisms in Malaysians

Summary Three human saliva genetic markers, namely, salivary peroxidase (SAPX), Pm, and Ph proteins, were investigated in the three major ethnic groups of Malaysia: Malays, Chinese, and Indians.For Pm, the allelic frequencies of Pm ⁺ for Malays, Chinese, and Indians are 0.385±0.030, 0.282±0.026, and 0.289±0.026 respectively. For Ph, the allelic frequencies of Ph ⁺ are 0.082±0.016 for Malays, 0.109±0.017 for Chinese, and 0.062±0.013 for Indians. For SAPX, the allelic frequencies of SAPX ¹ in Malays, Chinese, and Indians are 0.762±0.027, 0.755±0.027, and 0.723±0.026 respectively.     

Human liver aldehyde dehydrogenase in Chinese and Asiatic Indians: Gene deletion and its possible implications in alcohol metabolism

Two separate human liver aldehyde dehydrogenases exist which show differences in substrate specificity, cation inhibition or activation, and molecular weight. In this paper we report a common absence of enzyme 2 in Chinese which may be taken to indicate a gene deletion coding for this enzyme. The possible implication of this gene deletion among Chinese is discussed.     

Synthèse des l-fucose et l-(3-2H)fucose à partir du d-mannose

Oxidation with the dimethyl sulfoxide-acetic anhydride reagent of methyl 2-O-acetyl-4,6-O-benzylidene-α-d-mannopyranoside, obtained in quantitative yield from the corresponding 4,6-benzylidene acetal by stereoselective opening of a 2,3-orthoester, led in good yield to methyl 2-O-acetyl-4,6-O-benzylidene-α-d-arabino-hexopyranosid-3-ulose, which was reduced with either sodium borohydride or sodium borodeuteride into a methyl 4,6-O-benzylidene-α-d-altropyranoside or its 3-²H derivative. A sequence involving a C-6 halogenation-dehydrohalogenation followed by catalytic hydrogenation of the resulting methyl 6-deoxy-α-d-arabino-hex-5-enopyranoside gave methyl 6-deoxy-β-l-galactopyranoside (methyl β-l-fucopyranoside) and then α-l-fucose, with an overall yield of 24% with respect to the starting methyl α-d-mannopyranoside.     

Biochemical genetic markers in the Kadazans of Sabah,Malaysia

Summary Kadazans, the largest indigenous group in Sabah, northern Borneo, were surveyed for glyoxalase I, phosphoglucomutase I, red cell acid phosphatase, esterase D, adenosine deaminase, soluble glutamate pyruvate transaminase, soluble glutamate oxaloacetate transaminase, 6-phosphogluconate dehydrogenase, uridine monophosphate kinase, adenylate kinase, peptidase B and D, superoxide dismutase, C₅, group specific component, haptoglobin and transferrin.Kadazans were found to be polymorphic for GLOI, PGMI, RCAP, esterase D, ADA, s-Gpt, 6PGD, UMPK, Gc, C₅, haptoglobin and peptidase B. Rare variants were found for transferrin and peptidase D. No variant was found for s-Got, SOD and AK.     

ZAKβ antagonizes and ameliorates the cardiac hypertrophic and apoptotic effects induced by ZAKα

ZAK (sterile alpha motif and leucine zipper containing kinase AZK), a serine/threonine kinase with multiple biochemical functions, has been associated with various cell processes, including cell proliferation, cell differentiation, and cardiac hypertrophy. In our previous reports, we found that the activation of ZAKα signaling was critical for cardiac hypertrophy. In this study, we show that the expression of ZAKα activated apoptosis through both a FAS‐dependent pathway and a mitochondria‐dependent pathway by subsequently inducing caspase‐3. ZAKβ, an isoform of ZAKα, is dramatically expressed during cardiac hypertrophy and apoptosis. The interaction between ZAKα and ZAKβ was demonstrated here using immunoprecipitation. The results show that ZAKβ has the ability to diminish the expression level of ZAKα. These findings reveal an inherent regulatory role of ZAKβ to antagonize ZAKα and to subsequently downregulate the cardiac hypertrophy and apoptosis induced by ZAKα.