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61.
Kwon M Yoon CS Jeong W Rhee SG Waisman DM 《The Journal of biological chemistry》2005,280(25):23584-23592
The binding of plasminogen activators and plasminogen to the cell surface results in the rapid generation of the serine protease plasmin. Plasmin is further degraded by an autoproteolytic reaction, resulting in the release of an angiostatin, A61 (Lys78-Lys468). Previously, we demonstrated that the annexin A2-S100A10 heterotetramer (AIIt) stimulates the release of A61 from plasmin by promoting the autoproteolytic cleavage of the Lys468-Gly469 bond and reduction of the plasmin Cys462-Cys541 disulfide (Kwon, M., Caplan, J. F., Filipenko, N. R., Choi, K. S., Fitzpatrick, S. L., Zhang, L., and Waisman, D. M. (2002) J. Biol. Chem. 277, 10903-10911). Mechanistically, it was unclear if AIIt promoted a conformational change in plasmin, resulting in contortion of the plasmin disulfide, or directly reduced the plasmin disulfide. In the present study, we show that AIIt thiols are oxidized during the reduction of plasmin disulfides, establishing that AIIt directly participates in the reduction reaction. Incubation of HT1080 cells with plasminogen resulted in the rapid loss of thiol-specific labeling of AIIt by 3-(N-maleimidopropionyl)biocytin. The plasminogen-dependent oxidation of AIIt could be attenuated by thioredoxin. Thioredoxin reductase catalyzed the transfer of electrons from NADPH to the oxidized thioredoxin, thus completing the flow of electrons from NADPH to AIIt. Therefore, we identify AIIt as a substrate of the thioredoxin system and propose a new model for the role of AIIt in the redox-dependent processing of plasminogen and generation of an angiostatin at the cell surface. 相似文献
62.
Annexin A3 is a potential angiogenic mediator 总被引:7,自引:0,他引:7
Park JE Lee DH Lee JA Park SG Kim NS Park BC Cho S 《Biochemical and biophysical research communications》2005,337(4):1283-1287
Angiogenesis is a complex process that is regulated by a variety of angiogenic activators and inhibitors. Disruption of the balanced angiogenesis leads to the progress of diseases such as tumor growth, rheumatoid arthritis, and various blood vessel-related disorders. Even though a number of proteins involved in angiogenesis have been identified so far, more protein factors remain to be identified due to complexity of the process. Here we report that annexin A3 (ANXA3) induces migration and tube formation of human umbilical vein endothelial cells. High level of vascular endothelial growth factor (VEGF), a prominent angiogenic factor, is also detected in conditioned medium obtained from cells transfected with ANXA3 expression plasmid. Reporter assays show that ANXA3 enhances hypoxia-inducible factor-1 (HIF-1) transactivation activity. Taken together, our results suggest that ANXA3 is a novel angiogenic factor that induces VEGF production through the HIF-1 pathway. 相似文献
63.
Hydrogen peroxide (H2O2) is an incompletely reduced metabolite of oxygen that has a diverse array of physiological and pathological effects within
living cells depending on the extent, timing, and location of its production. Characterization of the cellular functions of
H2O2 requires measurement of its concentration selectively in the presence of other oxygen metabolites and with spatial and temporal
fidelity in live cells. For the measurement of H2O2 in biological fluids, several sensitive methods based on horseradish peroxidase and artificial substrates (such as Amplex
Red and 3,5,3’5’-tetramethylbenzidine) or on ferrous oxidation in the presence of xylenol orange (FOX) have been developed.
For measurement of intracellular H2O2, methods based on dihydro compounds such as 2’,7’-dichlorodihydrofluorescein that fluoresce on oxidation are used widely
because of their sensitivity and simplicity. However, such probes react with a variety of cellular oxidants including nitric
oxide, peroxynitrite, and hypochloride in addition to H2O2. Deprotection reaction-based probes (PG1 and PC1) that fluoresce on H2O2-specific removal of a boronate group rather than on nonspecific oxidation have recently been developed for selective measurement
of H2O2 in cells. Furthermore, a new class of organelle-targetable fluorescent probes has been devised by joining PG1 to a substrate
of SNAP-tag. Given that SNAP-tag can be genetically targeted to various subcellular organelles, localized accumulation of
H2O2 can be monitored with the use of SNAP-tag bioconjugation chemistry. However, given that both dihydro- and deprotection-based
probes react irreversibly with H2O2, they cannot be used to monitor transient changes in H2O2 concentration. This drawback has been overcome with the development of redox-sensitive green fluorescent protein (roGFP)
probes, which are prepared by the introduction of two redox-sensitive cysteine residues into green fluorescent protein; the
oxidation of these residues to form a disulfide results in a conformational change of the protein and altered fluorogenic
properties. Such genetically encoded probes react reversibly with H2O2 and can be targeted to various compartments of the cell, but they are not selective for H2O2 because disulfide formation in roGFP is promoted by various cellular oxidants. A new type of H2O2-selective, genetically encoded, and reversible fluorescent probe, named HyPer, was recently prepared by insertion of a circularly
permuted yellow fluorescent protein (cpYFP) into the bacterial peroxide sensor protein OxyR. 相似文献
64.
65.
The catalytic cysteine of certain members of the peroxiredoxin (Prx) family can be hyperoxidized to cysteinesulfinic acid during reduction of peroxides. Sulfiredoxin is responsible for the ATP-dependent reduction of cysteinesulfinic acid (SO2H) of hyperoxidized Prx. Here we report the NMR solution structure of human sulfiredoxin (hSrx), both with and without bound ATP, and we model the complex of ATP-bound hSrx with Prx. Binding ATP causes only small changes in the NMR structure of hSrx, and the bound ATP conformation is quite similar to that seen for the previously reported X-ray structure of the ADP-hSrx complex. Although hSrx binds ATP, it does not catalyze hydrolysis by itself and has no catalytic acid residue typical of most ATPase and kinase family proteins. For modeling the complex, the ATP-bound hSrx was docked to hyperoxidized Prx II using EMAP of CHARMM. In the model complex, Asn186 of Prx II (Asp187 of Prx I) is in contact with the hSrx-bound ATP beta- and gamma-phosphate groups. Asp187 of Prx I was mutated to alanine and asparagine, and binding and activity of the mutants with hSrx were compared to those of the wild type. For the D187N mutant, both binding and hydrolysis and reduction activities were comparable to those of the wild type, whereas for D187A, binding was unimpaired but ATP hydrolysis and reduction did not occur. The modeling and mutagenesis analyses strongly implicate Asp187 of Prx I as the catalytic residue responsible for ATP hydrolysis in the cysteinesulfinic acid reduction of Prx by hSrx. 相似文献
66.
Dogmatic views of how proteins and other cellular components may traffic within and between eukaryotic cells have been challenged in the past few years. Beyond the classical secretory/exocytic pathway and its established players, other pathways of cell surface membrane transport, generally termed “unconventional secretion,” are now better understood. More insights have also been gleaned on the roles of secreted or shedding microvesicles, either exosomal or ectosomal in origin, in unconventional secretion. Recent works have also revealed key molecular components, particularly the Golgi reassembly stacking protein (GRASP), and the importance of stress‐induced autophagy, in unconventional exocytic transport. This GRASP and autophagy‐dependent (GAD) mode appears to underlie the unconventional exocytosis of many soluble and membrane cargoes. Likewise, recent findings have revealed transport processes that contrast the classically known mitochondria import, namely vesicular transport from the mitochondria to peroxisomes and lysosomes. Mitochondria‐peroxisomal targeting of mitochondria‐derived vesicles appears to involve the retromer complex, which was classically associated with endosome‐Golgi membrane traffic. The routes of intracellular membrane transport and communications between eukaryotic organelles now appear far more complex that one would have imagined 10 years ago. J. Cell. Physiol. 227: 3722–3730, 2012. © 2012 Wiley Periodicals, Inc. 相似文献
67.
Hong IH Han JY Goo MJ Hwa SY Ki MR Park JK Hong KS Hwang OK Kim TH Yoo SE Jeong KS 《Histology and histopathology》2012,27(2):171-179
Senescent cells have been observed in certain aged or damaged tissues. However, the information about the effects of aging on liver cells is limited. In the present study, we have examined age-related histological changes in the livers of senescence marker protein knockout (SMP30-/-) mice, which are considered as a murine aging model due to the more sensitive response to apoptotic reagents and due to their shorter life span. In livers of old SMP30-/- mice, numerous hepatic stellate cells (HSCs) were hypertrophic and contained abundant microvesicular lipid droplets in cytoplasm. We have found that the expression of peroxisome proliferators-activated receptor γ (PPARγ), which is a protein related to lipid metabolism and HSC quiescence, was increased in hypertrophic HSCs by aging and vitamin C (VC) deficiency, whereas these phenomena were dramatically reduced by antioxidant treatment. Therefore, these prominent phenotypic changes can be considered as aging markers in the livers of animals which are subjected to antioxidant property evaluation. 相似文献
68.
Jung TY Li D Park JT Yoon SM Tran PL Oh BH Janeček Š Park SG Woo EJ Park KH 《The Journal of biological chemistry》2012,287(11):7979-7989
Staphylothermus marinus maltogenic amylase (SMMA) is a novel extreme thermophile maltogenic amylase with an optimal temperature of 100 °C, which hydrolyzes α-(1-4)-glycosyl linkages in cyclodextrins and in linear malto-oligosaccharides. This enzyme has a long N-terminal extension that is conserved among archaic hyperthermophilic amylases but is not found in other hydrolyzing enzymes from the glycoside hydrolase 13 family. The SMMA crystal structure revealed that the N-terminal extension forms an N' domain that is similar to carbohydrate-binding module 48, with the strand-loop-strand region forming a part of the substrate binding pocket with several aromatic residues, including Phe-95, Phe-96, and Tyr-99. A structural comparison with conventional cyclodextrin-hydrolyzing enzymes revealed a striking resemblance between the SMMA N' domain position and the dimeric N domain position in bacterial enzymes. This result suggests that extremophilic archaea that live at high temperatures may have adopted a novel domain arrangement that combines all of the substrate binding components within a monomeric subunit. The SMMA structure provides a molecular basis for the functional properties that are unique to hyperthermophile maltogenic amylases from archaea and that distinguish SMMA from moderate thermophilic or mesophilic bacterial enzymes. 相似文献
69.
70.
Roles of four Arabidopsis u-box e3 ubiquitin ligases in negative regulation of abscisic Acid-mediated drought stress responses 总被引:1,自引:0,他引:1
DH Seo MY Ryu F Jammes JH Hwang M Turek BG Kang JM Kwak WT Kim 《Plant physiology》2012,160(1):556-568
AtPUB18 and AtPUB19 are homologous U-box E3 ubiquitin ligases in Arabidopsis (Arabidopsis thaliana). AtPUB19 is a negative regulator of abscisic acid (ABA)-mediated drought responses, whereas the role of AtPUB18 in drought responses is unknown. Here, loss-of-function and overexpression tests identified AtPUB18 as a negative regulator in ABA-mediated stomatal closure and water stress responses. The atpub18-2atpub19-3 double mutant line displayed more sensitivity to ABA and enhanced drought tolerance than each single mutant plant; therefore, AtPUB18 and AtPUB19 are agonistic. Stomatal closure of the atpub18-2atpub19-3 mutant was hypersensitive to hydrogen peroxide (H(2)O(2)) but not to calcium, suggesting that AtPUB18 and AtPUB19 exert negative effects on the ABA signaling pathway downstream of H(2)O(2) and upstream of calcium. AtPUB22 and AtPUB23 are other U-box E3 negative regulators of drought responses. Although atpub22atpub23 was more tolerant to drought stress relative to wild-type plants, its ABA-mediated stomatal movements were highly similar to those of wild-type plants. The atpub18-2atpub19-3atpub22atpub23 quadruple mutant exhibited enhanced tolerance to drought stress as compared with each atpub18-2atpub19-3 and atpub22atpub23 double mutant progeny; however, its stomatal behavior was almost identical to the atpub18-2atpub19-3 double mutant in the presence of ABA, H(2)O(2), and calcium. Overexpression of AtPUB18 and AtPUB19 in atpub22atpub23 effectively hindered ABA-dependent stomatal closure, but overexpression of AtPUB22 and AtPUB23 in atpub18-2atpub19-3 did not inhibit ABA-enhanced stomatal closure, highlighting their ABA-independent roles. Overall, these results suggest that AtPUB18 has a linked function with AtPUB19, but is independent from AtPUB22 and AtPUB23, in negative regulation of ABA-mediated drought stress responses. 相似文献