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1.
Four cyclic octapeptides were designed from ascidiacyclamide [cyclo(–Ile–Oxz–D ‐Val– Thz–)2] (ASC, 1 ) to investigate the effects of oxazoline (Oxz) and thiazole (Thz) rings on the structures and cytotoxicities of the peptides. cyclo(–Ile–Thz–D ‐Val–Oxz–)2 ( 2 ) had the same number of Oxz and Thz rings as ASC, but the ring positions were switched. cyclo(–Ile–Oxz–D ‐Val–Thz–Ile–Thz–D ‐Val–Thz–) ( 3 ) and cyclo(–Ile–Thz–D ‐Val–Oxz–Ile–Thz–D ‐Val–Thz–) ( 4 ) contained one Oxz and three Thz rings within the molecule. All Oxz rings were substituted with Thz in cyclo(–Ile–Thz–D ‐Val–Thz–)2 ( 5 ). These analogues had new Oxz and Thz blocks forming the 24‐membered ring. Based on CD spectra and X‐ray diffraction analyses, the structures of all four analogues were classified as square ASC forms. But the structures of 2 and 5 differed from the original square form of 1 , and they showed no cytotoxicity. The structure of 3 was very similar to that of 1 , and 3 showed 10 times greater cytotoxicity than 1 . Although no definite structure of 4 was obtained, it showed three times greater cytotoxicity than 1 . It appears that the position and number of Oxz residues are essential determinants in the structure‐cytotoxicity relationship of ASC analogues.  相似文献   

2.
Extensive conformational analysis of a series of β‐alkyl substituted cyclopeptides—cyclo(Pro1–Xaa2–Nle3–Ala4–Nle5–Pro6–Xaa7–Nle8–Ala9–Nle10) and cyclo[Pro1–Xaa2–Nle3–(Cys4– Nle5–Pro6–Xaa7–Nle8–Cys9)–Nle10] as well as their corresponding unsubstituted core structures cyclo(Pro1–Xaa2–Ala3–Ala4–Ala5–Pro6–Xaa7–Ala8–Ala9–Ala10) and cyclo(Pro1–Xaa2–Ala3–Cys4– Ala5–Pro6–Xaa7–Ala8–Cys9–Ala10) has been performed employing both the ECEPP/2 and the MAB force fields (Xaa = Gly, L ‐Ala, D ‐Ala, Aib, and D ‐Pro). Results show that (a) possible three‐dimensional structures of the cyclo(Pro1–Gly2–Lys3–Ala4–Lys5–Pro6–Gly7–Lys8–Ala9–Lys10) molecule are not limited to a single extended “rectangular” conformation with all Lys side chains oriented at the same side of the molecule; (b) conformational equilibrium in monocyclic analogues obtained by replacements of conformationally flexible Gly residues for L ‐Ala, D ‐Ala, Aib, or D ‐Pro is not significantly shifted towards the target “rectangular” conformational type; and (c) introduction of disulfide bridges between positions 4 and 9 is a very powerful way to stabilize the target conformations in the resulting bicyclic molecules. These findings form the basis for further design of rigidified regioselectively addressable functionalized templates with many application areas ranging from biostructural to diagnostic purposes. © 1999 John Wiley & Sons, Inc. Biopoly 50: 361–372, 1999  相似文献   

3.
W L Mattice 《Biopolymers》1974,13(1):169-183
The circular dichroism of Ac–Ala–NHMe, cyclo(–Ala–Ala–), Ac–Ala–OMe, Ac–Ala–Ala–OMe, and Ac–Ala–Ala–Ala–OMe has been measured in water and in aqueous salt solutions as a function of temperature. Only cyclo(–Ala–Ala–) exhibits circular dichroism which is independent of temperature. Each of the linear derivatives of L -alanine exhibits a positive circular dichroism in the range 208–218 nm at 15°C in water. Heating reduces the intensity of the positive circular dichroism, and only Ac–Ala–OMe retains positive circular dichroism at 75°C in water. Isothermal addition of salts produces changes in the circular dichroism of linear derivatives of L -alanine which resemble those seen on heating. The relative effectiveness of the salts tested, at a concentration of 4M, is LiCl ? KCl = NaCl < MgCl2 ? CaCl2 ? NaClO4. The circular dichroism of cyclo(–Ala–Ala–) is also affected by the salts. Extrapolation of the results obtained with Ac–Ala–OMe, Ac–Ala–Ala–OMe, and Ac–Ala–Ala–Ala–OMe to a long polypeptide with a –CH2R side chain in the L -configuration leads to the conclusion that this polypeptide should exhibit a temperature-dependent salt-sensitive positive circular dichroism between 208 and 218 nm when it exists as a statstical coil.  相似文献   

4.
Fifteen new peptide derivatives of ?-aminocaproic acid (EACA) containing the known fragment –Ala–Phe–Lys– with an affinity for plasmin were synthesised in the present study. The synthesis was carried out a solid phase. The following compounds were synthesised: H–Phe–Lys–EACA–X, H–d-Ala–Phe–Lys–EACA–X, H–Ala–Phe–Lys–EACA–X, H–d-Ala–Phe–EACA–X and H–Ala–Phe–EACA–X, where X = OH, NH2 and NH–(CH2)5–NH2. All peptides, except for those containing the sequence H–Ala–Phe–EACA–X, displayed higher inhibitory activity against plasmin than EACA. The most active and selective inhibitor of plasmin was the compound H–d-Ala–Phe–Lys–EACA–NH2 which inhibited the amidolytic activity of plasmin (IC50 = 0.02 mM), with the antifibrinolytic activity weaker than EACA. The resulting peptides did not affect the viability of fibroblast cells, colon cancer cell line DLD-1, breast MCF-7 and MDA-MB-231 cell lines.  相似文献   

5.
6.
Phosphofructokinase‐1 from Saccharomyces cerevisiae is composed of two types of subunits, α and β. Subunit‐specific monoclonal antibodies were raised to elucidate structural and functional properties of both subunits. One monoclonal antibody, α‐F3, binds to an epitope either at the C‐terminal or at the N‐terminal part of the α‐polypeptide chain. By screening a heptapeptide library with this monoclonal antibody, a set of heptapeptides was selected, which contained the consensus sequences D–A–F and D–S–F. Two heptapeptides with these motifs were synthesized in order assess their capacity to inhibit the binding of antibody α‐F3 to native phosphofructokinase‐1. The peptide G–I–K–D–A–F–L inhibited the binding more strongly (IC50 = 1.5 µM) than the peptide A–P–W–H–D–S–F (IC50 = 33.3 µM). Sequence matching revealed the presence of the D–A–F motif in the polypeptide chain of phosphofructokinase‐1 at amino acid position 172–174. As a control, the nonapeptide A–P–T–S–K–D–A–F–L which corresponds to the sequence of the putative epitope was tested in the inhibition assay. In view of the high inhibitory capacity (IC50 = 0.3 µM) it was concluded that this nonapeptide represents the continuous epitope of phosphofructokinase‐1 that is recognized by antibody α‐F3. Copyright © 1999 John Wiley & Sons, Ltd.  相似文献   

7.
《Journal of Asia》2021,24(3):925-932
Antheraea mylitta Drury (Lepidoptera: Saturniidae) is a tropical semi-domesticated wild tasar silkworm reared by marginal tribal farmers of India. Due to improper egg laying frequency, oviposition is generally kept for three continuous days after amputating the gravid moth wings (W) in earthen cups (C). In order to systematize the oviposition frequency, wing cut with leg cut (WL) was performed in ecorace Daba trivoltine (DTV) completing three life-cycles in a year. Oviposition of (C)WL was observed in all three grainages during the year 2020 and compared with (C)W moths. Oviposition was also accomplished on plain paper sheets (S). It is observed that (C)W obtained 63–67% and (C)WL obtained 72–80% egg laying on first day. Similarly, (S)W and (S)WL obtained 68–71% and 74–83% on first day. Further, significant high oviposition was observed within first four hours in both earthen cups and on paper sheets by WL moths laying 49–69% and 55–65% eggs compared to W laying 25–45% and 39–44% eggs, respectively. A total of 44–51, 47–54, 44–48 and 46–52 eggs/g moth weight was obtained in (C)W, (C)WL, (S)W and (S)WL, respectively in three consecutive grainage. Oviposition of W moths in earthen cups and on paper sheets are not significantly different indicating earthen cups in contemporary tasar grainage could be replaced with paper sheets. Thus, the paper demonstrates for the first time a fast, efficient and scalable cellular oviposition of A. mylitta on paper sheets comparable to Bombyx mori.  相似文献   

8.
Choline acetyltransferase is critical in the synthesis of acetylcholine and regulation of cholinergic neuron functions. We recently reported association of the encoding gene ChAT with both smoking cessation and nicotine dependence (ND) in two independent European American (EA) samples; however, in the replication sample, only limited SNPs partially covering the gene were examined. In this study, we examined the association of 14 SNPs, which cover the entire gene, with ND, assessed by smoking quantity (SQ), heaviness of smoking index (HSI), and Fagerström Test for ND (FTND), in 2,037 subjects from 602 families of African American (AA) or EA origin. Individual SNP-based association analysis revealed that five SNPs showed nominal association with at least one ND measure in one of the samples (P = 0.022–0.042); none remained significant after correction for multiple testing. Haplotype-based association analysis revealed that haplotypes G–G–A–C, formed by rs1880676–rs3810950–rs10082479–rs8178990 (P = 0.005–0.0178), and G–G–T–C–G–C, formed by rs1880676–rs3810950–rs10082479–rs8178990–rs3793790–rs12266458 (P = 0.00247–0.00468), displayed significant association with all three ND measures in the AA sample, as did haplotype T–C–G–A–T, formed by rs12266458–rs11101191–rs8178991–rs4838544–rs4838547 (P = 0.00741–0.0103), in the EA sample. All these detected haplotype-based associations remained significant after correction for all major haplotypes for a given SNP combination. Together, our findings, in conjunction with the previous report of the association, warrant further investigation of ChAT in ND.  相似文献   

9.
This study describes the isolation of angiotensin I converting enzyme and antioxidative peptides from head protein hydrolysate of red scorpionfish (Scorpaena notata) prepared by treatment with a protease from the fungus Penicillium digitatum. After ultrafiltration, three peptides were isolated by a two-step procedure: size exclusion chromatography on a Toyopearl HW-40 followed by reversed-phase high performance liquid chromatography (RP-HPLC) with a high purification yield of 2.22 mg of peptide/g of initial protein. Active peptides were then identified by nanoscale liquid chromatography coupled to tandem mass spectrometry (nanoLC/MS–MS), corresponding to the following sequences: Gln–Gln–Pro–His–Ser–Arg–Ser–Lys–Gly–Phe–Pro–Gly–Pro (1424.724 Da), Gly–Gln–Lys–Ser–Val–Pro–Glu–Val–Arg (1000.565 Da) and Val–Glu–Gly–Lys–Ser–Pro–Asn–Val (830.448 Da). Peptides D-I, E-I and F-I showed high angiotensin-I converting enzyme inhibitory activity with an IC50 values of 0.98, 1.69 and 1.44 µM, respectively as well as a synergistic antioxidant activity between the different fractions. Thus, we have demonstrated that underutilized wastes can be valorized by production of peptides that can be used as potential therapeutic compounds active against oxidative stress and hypertension.  相似文献   

10.
Alpha-bag cell peptide [α-BCP (Ala-Pro-Arg-Leu-Arg-Phe-Tyr-Ser-Leu)] is a neurotransmitter that mediates bag cell-induced inhibition of left-upper-quadrant (LUQ) neurons L2, L3, L4, and L6 in the abdominal ganglion of Aplysia. Our recent biochemical studies have shown that α-BCP[1–9] is cleaved into α-BCP[1–2], [3–9], [1–5], [6–9], and [7–9] by a combination of three distinct peptidase activities located within the extracellular spaces of the CNS: A diaminopeptidase-IV (DAP-IV)-like enzyme cleaves α-BCP[1–9] at the 2–3 peptide bond; a neutral metalloendopeptidase (NEP)-like enzyme cleaves either α-BCP[1–9] or α-BCP[3–9] at the 5–6 bond; an aminopeptidase M-II (APM-II)-like enzyme cleaves α-BCP[6–9] at the 6–7 bond, but cleaves neither α-BCP[1–9], nor the other ganglionic peptidase products. To further understand the manner in which α-BCP is inactivated after release, that is loses its electro-physiological activity, we studied its structure-activity relationship by recording intracellularly from LUQ neurons in isolated abdominal ganglia that were arterially perfused with peptides dissolved in artificial sea water. The effects of α-BCP[1–9] and 15 of its fragments ([1–8], [1–7], [1–6], [1–5], [2–9], [3–9], [3–8], [6–9], [7–9], [8–9], [6–7], [6–8], [1–2], Phe, Tyr) indicated that the sequence Phe6-Tyr7 was both necessary and sufficient to produce LUQ inhibitory activity. The combined results of our electrophysiological and biochemical studies strongly suggest that α-BCP[1–9] is inactivated by the serial actions of the NEP-like and APM-II-like peptidases; that is, the NEP-like enzyme yields an electro-physiologically active product, α-BCP[6–9], that is cleaved by the APM-II-like enzyme to yield inactive α-BCP[7–9]. Furthermore, because α-BCP[6–9] is more active than α-BCP[1–9], cleavage by the NEP-like enzyme potentiates α-BCP's activity. © 1992 John Wiley & Sons, Inc.  相似文献   

11.
Using the chain build-up procedure based on the program ECEPP, we have computed the lowest energy structures for two terminally blocked subsequences from the antigenic circumsporozoite protein of Plasmodium berghei, that is known to cause malaria in animals. The full antigenic sequence is an octapeptide proline-rich tandem repeat, (Pro–Pro–Pro–Pro–Asn–Pro–Asn–Asp)2. We computed the structures for the first octapeptide plus one Pro from the second octapeptide, terminally blocked CH3CO–Pro–Pro–Pro–Pro–Asn–Pro–Asn–Asp–Pro–NHCH3 as well as the first octpeptide with an additional three Pro residues from the adjoining unit, i.e., CH3CO–Pro–Pro–Pro–Pro–Asn–Pro–Asn–Asp–Pro–Pro–Pro–NHCH3. We find that the first sequence adopts a number of different low energy structures, the most probable of which has a probability of occurrence of 56 %. Addition of two more Pro residues results in the adoption a single, unique lowest energy structure that has a probability of occurrence of over 95 % without solvation effects and 86 % when solvation effects are included in the calculations. We predict that this structure may be the one recognized as a major antigenic determinant.  相似文献   

12.
Twenty tryptic peptides were isolated from the performic acid-oxidized He chain of ricin D by Dowex 1 × 2 column chromatography followed by paper chromatography. The amino acids contained in these peptides accounted for 218 out of 266 residues in the whole protein. The amino acid sequences of nine peptides were determined by manual liquid phase or automatic solid phase Edman degradation, and N- and C-terminal sequences of the He chain of ricin D were established to be NH2–Ile–Phe–Pro–Lys–Gln–Tyr–Pro–Ile–Ile– and Cys–Ala–Pro–Pro–Pro–Ser–Ser–Gln–Phe, respectively.  相似文献   

13.
An α-mannosidase was purified from developing Ginkgo biloba seeds to apparently homogeneity. The molecular weight of the purified α-mannosidase was estimated to be 120 kDa by SDS–PAGE in the presence of 2-mercaptoethanol, and 340 kDa by gel filtration, indicating that Ginkgo α-mannosidase may function in oligomeric structures in the plant cell. The N-terminal amino acid sequence of the purified enzyme was Ala–Phe–Met–Lys–Tyr–X–Thr–Thr–Gly–Gly–Pro–Val–Ala–Gly–Lys–Ile–Asn–Val–His–Leu–. The α-mannosidase activity for Man5GlcNAc1 was enhanced by the addition of Co2+, but the addition of Zn2+, Ca2+, or EDTA did not show any significant effect. In the presence of cobalt ions, the hydrolysis rate for pyridylaminated Man6GlcNAc1 was significantly faster than that for pyridylaminated Man6GlcNAc2, suggesting the possibility that this enzyme is involved in the degradation of free N-glycans occurring in developing plant cells (Kimura, Y., and Matsuo, S., J. Biochem., 127, 1013–1019 (2000)). To our knowledge, this is the first report showing that plant cells contain an α-mannosidase, which is activated by Co2+ and prefers the oligomannose type free N-glycans bearing only one GlcNAc residue as substrate.  相似文献   

14.
Peptide YY 3–36-amide (PYY3–36) is a peptide hormone, which is known to decrease appetite and food-intake by activation of the Y2 receptor. The current studies were designed to identify the metabolites of PYY3–36 in mini-pig and rhesus monkey. Plasma samples were analyzed by high resolution LC–MS (and MS/MS) in order to unambiguously identify the metabolites of PYY3–36. In summary, the metabolism of PYY3–36 was similar in mini-pig and rhesus monkey. Several metabolites were identified and PYY3–34 was identified at the highest levels in plasma. In addition, mini-pigs were also dosed with PYY1–36-amide, PYY3–35, PYY3–34 and [N-methyl 34Q]-PYY3–36-amide in order to investigate the mechanisms by which PYY was metabolized. PYY3–35 was rapidly converted to PYY3–34 whereas dosing of PYY3–34 to mini-pigs only showed circulating degradation products at low levels, i.e., PYY3–34 was metabolically more stable than PYY3–36 and PYY3–35. [N-methyl 34Q]-PYY3–36-amide was hypothesized to be stable toward cleavage between 34Q and 35R and after i.v. administration to mini-pigs, one major cleavage product was identified as [N-methyl 34Q]-PYY3–35. Overall, this showed that cleavage between 35R and 36Y was possible as well as between 34Q and 35R (as shown for PYY3–35), which indicated that metabolism of PYY3–36 to PYY3–34 may be a two-step process. PYY1–36 was also dosed to mini-pigs, which showed that PYY1–36 was metabolized in the C-terminal as PYY3–36. The overall degradation pattern of PYY1–36 was more complex due to the simultaneous enzymatic degradation in the N-terminal to form PYY2–34/36 and PYY3–34/36. In vitro incubations with heparin stabilized plasma showed that PYY3–36 was degraded with a half-life of 175 min, whereas incubations with PYY3–35 (half-life of 6 min) showed a rapid formation of PYY3–34. In conclusion, the present studies showed that PYY3–36 underwent enzymatic degradation in the C-terminal part and that the major circulating metabolite was PYY3–34. Furthermore, it may be a sequential two-step process leading to the formation of PYY3–35 and subsequently the metabolically more stable PYY3–34.  相似文献   

15.
While the Fe2+–dithiocarbamate complexes have been commonly used as NO traps to estimate NO production in biological systems, these complexes can undergo complex redox chemistry. Characterization of this redox chemistry is of critical importance for the use of this method as a quantitative assay of NO generation. We observe that the commonly used Fe2+ complexes of N-methyl-D-glucamine dithiocarbamate (MGD) or diethyldithiocarbamate (DETC) are rapidly oxidized under aerobic conditions to form Fe3+ complexes. Following exposure to NO, diamagnetic NO–Fe3+ complexes are formed as demonstrated by the optical, electron paramagnetic resonance and gamma-resonance spectroscopy, chemiluminescence and electrochemical methods. Under anaerobic conditions the aqueous NO–Fe3+–MGD and lipid soluble NO–Fe2+–DETC complexes gradually self transform by reductive nitrosylation into paramagnetic NO–Fe2+–MGD complexes with yield of up to 50% and the balance is converted to Fe3+–MGD and nitrite. In dimethylsulfoxide this process is greatly accelerated. More efficient transformation of NO–Fe3+–MGD into NO–Fe2+–MGD (60–90% levels) was observed after addition of reducing equivalents such as ascorbate, hydroquinone or cysteine or with addition of excess Fe2+–MGD. With isotope labeling of the NO–Fe3+–MGD with 57Fe, it was shown that these complexes donate NO to Fe2+–MGD. NO–Fe3+–MGD complexes were also formed by reversible oxidation of NO–Fe2+–MGD in air. The stability of NO–Fe3+–MGD and NO–Fe2+–MGD complexes increased with increasing the ratio of MGD to Fe. Thus, the iron–dithiocarbamate complexes and their NO derivatives exhibit complex redox chemistry that should be considered in their application for detection of NO in biological systems.  相似文献   

16.
The life cycle of I. canis Nemeséri, 1959 was studied in experimentally infected dogs. Freshly sporulated oocysts were ovoid and 34–40 × 28–32 μm. The endogenous stages were found directly beneath the epithelium of the distal portion of the small intestinal villi. Most of the endogenous stages were in the lower 1/3 of the small intestine, but occasionally they were found in other portions of the small intestine. Three asexual generations were present. First-generation schizonts were 16–38 × 11–23 μm and contained 4–24 merozoites; mature 1st-generation merozoites were 8–11 × 3–5 μm. First-generation schizogony lasted up to 7 days after inoculation. Second-generation schizonts were 12–18 × 8–13 μm and contained up to 12 merozoites which were 11–13 × 3–5 μm. Second-generation schizogony was present on postinoculation days 6 and 7. Third-generation schizonts were formed by nuclear division of 2nd-generation merozoites. Most 2nd-generation merozoites underwent nuclear division without leaving the parasitophorous vacuole of the 2nd-generation schizont. Mature 3rd-generation schizonts were 13–38 × 8–24 μm and contained 6–72 merozoites. Third-generation merozoites were 8–13 × 1–3 μm. Third-generation schizogony was present on days 6–8 after inoculation. Mature macrogametes were 22–29 × 14–23 μm. Mature microgametocytes were 20–38 × 14–26 μm. Gametes were present on postinoculation days 7–10. Oocysts were present in tissue sections on postinoculation days 8–10 and 12. The prepatent period was 9–11 days.  相似文献   

17.
Novel sixgill shark (Hexanchus griseus) microsatellite loci were developed and tested on five shark species. A suite of microsatellite loci previously developed for lemon sharks (Negaprion brevirostris) was also tested. Data on 15 microsatellites are presented including primer sequences, number of alleles (a), observed (HO) and expected heterozygosities (HE), and FIS values for sixgill sharks (a = 10–69, HO = 0.24–1.00, HE = 0.76–0.96 and FIS = –0.21–0.60), sevengill sharks (Notorynchus cepedianus) (a = 6–40, HO = 0.20–0.73, HE = 0.59–0.94 and FIS = –0.47–0.58), Pacific spiny dogfish (Squalus acanthias) (a = 3–13, HO = 0.00–0.96, HE = 0.24–0.93 and FIS =–0.52–1.00), angle sharks (Squatina californica) (a = 1–4, HO = 0.00–1.00, HE = 0.60–1.00 and FIS =–1.00–0.25), and leopard sharks (Triakis semifasciata) (a = 3–16, HO = 0.20–1.00, HE = 0.53–0.92 and FIS = –0.57–1.00). A final suite of 14 microsatellites (13 developed from sixgill sharks and one from lemon sharks) were found to be polymorphic and conform to Hardy–Weinberg equilibrium within sixgill sharks.  相似文献   

18.
Ten new withanolides (110) and three artificial withanolides (1113) were isolated from the aerial parts of Tubocapsicum anomalum, together with five known analogues (1418). Their structures were determined on the basis of extensive spectroscopic and chemical methods. They include seven acnistin–type (14, 11, 14 and 15), three withajardin–type (57), and eight normal–type (810, 12, 13 and 1618) withanolides. Of normal–type withanolides, a chemical conversion from the 16α,17α–epoxywithanolide (16) to Δ13,14–16α–hydroxywithanolide (18) was achieved by Wagner–Meerwein rearrangement. All isolates were evaluated for their cytotoxicity against four human tumor cell lines (HCT–116, HepG2, MCF–7 and A375). Among them, compounds 13, 68, 14, 1618 showed cytotoxic activity with IC50 values of 0.24–8.71 μM.  相似文献   

19.
AimsMilk casein-derived bioactive tripeptides isoleucine–proline–proline (Ile–Pro–Pro) and valine–proline–proline (Val–Pro–Pro) lower blood pressure in animal models of hypertension and humans. In some studies, their angiotensin-converting enzyme (ACE)-inhibitory effect has been demonstrated. Besides classical ACE-angiotensin II-AT1-receptor pathway (ACE-Ang II- AT1), the significance of ACE2-angiotensin-(1–7)-Mas-receptor (ACE2-Ang-(1–7)-Mas) axis in the blood pressure regulation has now been acknowledged. The present study was aimed to further evaluate the renin–angiotensin system (RAS)-related vascular effects of Ile–Pro–Pro in vitro using rat mesenteric arteries.Main methodsSuperior mesenteric arteries of spontaneously hypertensive rat (SHR) were isolated, cut into rings and mounted in standard organ bath chambers. Endothelium-intact arterial rings were incubated in Krebs solution either with Ile–Pro–Pro, proline–proline (Pro–Pro), isoleucine (Ile), proline (Pro) or captopril for 6 h at + 37 °C and vascular reactivity was measured.Key findingsIn the presence of AT1-antagonist valsartan, Ang II induced vasodilatation, which was more pronounced in the arteries incubated with Ile–Pro–Pro (P < 0.05) compared to the other compounds. Ang-(1–7)-induced vasodilatation was augmented by Ile–Pro–Pro or Pro (P < 0.001 vs. control). Mas-receptor antagonist A-779 did not alter the responses. Ile–Pro–Pro and Pro augmented also bradykinin-induced relaxations (P < 0.001 vs. control). Control arteries and arteries incubated with captopril showed only slight relaxations at higher bradykinin concentrations.SignificanceCasein-derived tripeptide Ile–Pro–Pro and amino acid Pro enhance the vasodilatory effect of Ang-(1–7) and bradykinin. The role of ACE2-Ang–(1–7)-Mas axis in the modulation of vascular tone by these compounds seems probable.  相似文献   

20.
Spring (March–June) precipitation has been reconstructed since AD 1840 for the Rara National Park (RNP), western Nepal Himalaya using Abies spectabilis tree-ring width. The reconstruction accounts for 35.8% of the total variance of the instrumental precipitation from 1958 to 2012 and captured distinct wet and dry variability. The longest wet periods occurred during 1850–1862, 1878–1886, 1909–1917, 1971–1984 and 2000–2008 while dry periods were usually shorter and occurred during 1873–1877, 1921–1923, 1925–1929, 1951–1956, 1958–1962 and 1994–1996. Spectral analysis of the reconstruction shows significant peaks at periodicity ranging 2.4–6.5 year, suggesting a covariation in inter-annual variability similar to that of El Niño-Southern Oscillation (ENSO). Spectral analysis of the reconstruction shows significant quasi–cyclic (2.4–3.4 year) and multidecadal (24.8–39.2 year) periodicity, suggesting a potential association with El Niño-Southern Oscillation (ENSO) and Atlantic Multidecadal Oscillation (AMO).  相似文献   

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