Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P39060 (endostatin)
 2,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pichia pastoris, a methylotrophic yeast, is an efficient producer of recombinant proteins in which the heterologous gene is under the control of the methanol-induced AOX1 promoter. Hence, the accepted production procedure has two phases: In the first phase, the yeast utilizes glycerol and biomass is accumulated; in the second phase, the yeast utilizes methanol which is used both as an inducer for the expression of the recombinant protein and as a carbon source. Since the yeast is sensitive to methanol concentration, the methanol is supplied gradually to the growing culture. Three methanol addition strategies were evaluated for the purpose of optimizing recombinant endostatin production. Two strategies were based on the yeast metabolism; one responding to the methanol consumption using a methanol sensor, and the other responding to the oxygen consumption. In these two strategies, the methanol supply is unlimited. The third strategy was based on a predetermined exponential feeding rate, controling the growth rate at 0.02 h(-1), in this strategy the methanol supply is limited. Throughout the induction phase glycerol, in addition to methanol, was continuously added at a rate of 1 g L h(-1). Total endostatin production was similar in all three strategies, (400 mg was obtained from 3 L initial volume), but the amount of methanol added and the biomass produced were lower in the predetermined rate method. This caused the specific production of endostatin per biomass and per methanol to be 2 times higher in the predetermined rate than in the other two methods, making the growth control strategy not only more efficient but also more convenient for downstream processing.
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PMID:Effect of methanol feeding strategies on production and yield of recombinant mouse endostatin from Pichia pastoris. 1263

Angiogensis can be blocked by inhibitors such as endostatin and angiostatin. The kringle 5 fragment of plasminogen also has a potent inhibitory effect on endothelial cell proliferation and leads to the inhibition of angiogenesis. It has promise in anti-angiogenic therapy due to its small size and potent inhibitory effect. Preparation of kringle 5 has been achieved through the proteolysis of native plasminogen and recombinant DNA technology. Bacterially expressed recombinant kringle 5 is mainly insoluble and expressed at low level. The refolding yield is also low. To produce recombinant human kringle 5 in a large quantity, we have genetically modified a strain of Pichia pastoris. On methanol induction, this strain expressed and secreted biologically active, recombinant kringle 5. The expression level of the engineered strain in culture reached more than 300 mgl(-1). Purification was easily achieved by precipitation, hydrophobic and DEAE ion exchange chromatography. The recovery of recombinant kringle 5 was about 50% after purification. Yeast-expressed kringle 5 has a higher activity in anti-endothelial proliferation than bacterially expressed kringle 5.
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PMID:High level expression of kringle 5 fragment of plasminogen in Pichia pastoris. 1571 25

Earlier we had shown that on the 3 (rd) day of its administration to mice, indomethacin (18 mg kg (-1), P. O.) produced maximum stomach ulceration with a damage score of 3.46, which was reduced by a 3-day treatment with the methanol extract of Myristica malabarica (40 mg kg (-1), P. O.) and omeprazole (3 mg kg (-1), P. O.) to 0.95 and 0.82, respectively. Presently, we investigated the possible role of the test samples in modulating PG synthesis and angiogenesis for their healing action. The ulceration was found to be associated with suppression of PGE (2), VEGF and vWF VIII, and an increase in EGF and endostatin levels. Treatment with the plant extract reversed all these parameters accounting for its healing activity. However, despite providing similar healing, omeprazole did not alter these parameters.
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PMID:Myristica malabarica heals stomach ulceration by increasing prostaglandin synthesis and angiogenesis. 1901 6

Dimethylsulfide (CH(3)SCH(3)) is formed in anoxic freshwater sediments by biological methylation of methanethiol (CH(3)SH). We measured thiol methylation potential in low-pH, Sphagnum peat sediments from Alaska and Alabama by adding ethanethiol (CH(3)CH(2)SH) to peat slurries and quantifying the rate of ethylmethylsulfide (CH(3)CH(2)SCH(3)) formation. Thiol methylation potential ranged from 12 to 154 nM h(-1) and was significantly related to dimethylsulfide accumulation rates (P=0.0007; r(2)=0.48). Addition of methanol or syringic acid stimulated thiol methylation potential and dimethylsulfide accumulation rate, suggesting that these compounds could be methyl donors. Addition of acetate or its metabolic precursors (glucose or Sphagnum plant material) inhibited thiol methylation potential, but not carbon dioxide or methane production. Inhibition of methanogenesis with either 2-bromoethanesulfonic acid or KNO(3) consistently inhibited thiol methylation potential and dimethylsulfide accumulation. These results suggest that methanogens play a role in thiol methylation and therefore dimethylsulfide formation.
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PMID:Thiol methylation potential in anoxic, low-pH wetland sediments and its relationship with dimethylsulfide production and organic carbon cycling. 1971 41

L-leucine derived ligand (H(2)L(L-leu)), KOH, and Ni(II) salt in 2:2:1 ratio self-assembled into a rather large (approximately 13 A) supramolecular assembly with the formula [K{Ni(HL(L-leu))(2)}(3)](+) (1). Structural characterization showed three [Ni(HL(L-leu))(2)] units encapsulated K(+) similar to organic crown ethers/cryptand. Substituting Ni(II) with Cu(II) and K(+) with Na(+) in the above reaction resulted in a set of structurally identical assemblies with the general formula [M'{M(HL(L-leu))(2)}(3)](+), where M' is either K(+) or Na(+) and M is either Cu(II) or Ni(II); [Na{Ni(HL(L-leu))(2)}(3)]ClO(4) (2), Na{Ni(HL(L-leu))(2)}(3)]OTf (3), [K{Cu(HL(L-leu))(2)}(3)]ClO(4) (4), [Na{Cu(HL(L-leu))(2)}(3)]ClO(4) (5), [K{Cu(HL(L-leu))(2)}(3)]NO(3) (6). Electrospray Ionization (ESI)-mass spectra of the assemblies in MeOH showed the retention of assemblies in solution. Visible spectroscopic studies showed retention of assembly 1 in N,N-dimethylformamide (DMF) which is stable even after the addition of 5 equiv of [18]-crown-6. The assemblies in 2-6 show various degrees of dissociation to [M(HL(L-leu))(2)] and M', in stronger H-bonding methanol. The dissociation can be reversed upon addition of excess KNO(3)/NaNO(3) salt. Structural characterization of [Cu(HL(L-leu))(2)(MeCN)] (7) along with its transformation to [K{Cu(HL(L-leu))(2)}(3)](+) in the presence of K(+) salt demonstrated that the assembly formation proceeds through an alkali metal ion induced ligand reorientation within the [Cu(HL(L-leu))(2)] units which is further stabilized by six strong H-bonds holding the assembly. Interestingly, visible spectra of 1 and 2 shows that minor structural changes caused by replacing K(+) with Na(+) is sufficient to shift the d-d transition of Ni(II) by approximately 70 nm, thereby providing an indirect way of distinguishing K(+) and Na(+), none of which have spectroscopic signature in the visible range.
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PMID:Sodium and potassium ion directed self-assembled multinuclear assembly of divalent nickel or copper and L-leucine derived ligand. 1974 1

A systematic study of the behavior of several common mobile-phase volume markers using traditional and polar-group-containing reversed-phase stationary phases is presented. Examined mobile-phase volume markers include two neutral molecules, uracil and thiourea, concentrated (0.10 M) and dilute (0.0001 M) KNO(3), and D(2)O. Mobile-phase volumes are examined over the entire reversed-phase mobile-phase range of 100% water to 100% methanol or acetonitrile. The behavior of these mobile-phase volume markers is compared with a maximum theoretical value (i.e. the void volume), as determined by pycnometry. The data suggest that: (i) uracil begins to fail as a mobile-phase volume marker in mobile phases below about 40% strong solvent for polar group containing phases; (ii) in nearly all cases, the mobile-phase volume measured dynamically is smaller than the pycnometric void volume; (iii) a significant dependence of measured mobile-phase volume on salt concentration is seen on the polar endcapped phase, which is not observed on the traditional and embedded polar group phase; and (iv) D(2)O does not work well as a mobile-phase volume marker with polar-group-containing phases, possibly due to interaction with the stationary phase polar group.
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PMID:Comparison of common mobile-phase volume markers with polar-group-containing reversed-phase stationary phases. 2058 81

On the basis of the origin comparison of known endothelial genesis inhibitors, a 417-bp cDNA fragment was amplified from umbilical cord by RT-PCR and cloned into the expression vector pPIC9, followed by transformation into Pichia pastoris GS115. The resulted yeast was induced with methanol to express recombinant protein. The resulted protein was purified from culture broth and designated as EDI-8t. The in vitro study showed that EDI-8t, originated from collagen VIII, could specifically inhibit the growth and migration of bovine aortic endothelial cells (BAEC) stimulated by basic fibroblast growth factor (bFGF). The protein also exhibited the activity to cause cell apoptosis. In vivo EDI-8t showed the identical activity comparing with endostatin to inhibit the growth of liver tumor transplanted into nude mice. Interestingly, EDI-8t showed higher activity than endostatin to inhibit tumor growth in metastatic model of melanoma mice.
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PMID:[Endothelial genesis inhibitor-8t (EDI-8t) against tumor growth]. 2138 37