leupeptins and succinyl-leucyl-leucyl-valyl-tyrosyl-methylcoumarinamide

leupeptins has been researched along with succinyl-leucyl-leucyl-valyl-tyrosyl-methylcoumarinamide* in 7 studies

Other Studies

7 other study(ies) available for leupeptins and succinyl-leucyl-leucyl-valyl-tyrosyl-methylcoumarinamide

ArticleYear
Identification of plant-derived natural products as potential inhibitors of the Mycobacterium tuberculosis proteasome.
    BMC complementary and alternative medicine, 2014, Oct-15, Volume: 14

    The Mycobacterium tuberculosis (Mtb) proteasome has been established as a viable target for the development of anti-tuberculosis agents. In this study, the inhibitory activities of 100 plant-derived natural products on the Mtb proteasome were analyzed to identify novel potential inhibitors.. The fluorescent substrate Suc-Leu-Leu-Val-Tyr-AMC can be hydrolyzed by the proteasome to release free AMC, the fluorescence of which is proportional to the proteasome activity. The inhibitory activities of 100 natural products (each at a final concentration of 200 μM) were detected by this method using MG132 as a positive control.. Twelve of these natural products (10 of which were flavonoids) inhibited the activity of the Mtb proteasome by more than 65%. Comparison of the structural differences between the flavonoids with good inhibitory activity and those without inhibitory activity revealed that the hydroxyl at the flavonoid C ring C-3 or the hydroxyl/methoxyl at the flavonoid A ring C-6 were critical for the inhibition of proteasomal activity.. These data indicate that flavonoids represent a basis for rational structural design in the process of novel anti-tuberculosis drug discovery.

    Topics: Bacterial Proteins; Coumarins; Flavonoids; Leupeptins; Mycobacterium tuberculosis; Oligopeptides; Plant Extracts; Plants; Proteasome Endopeptidase Complex; Proteasome Inhibitors

2014
Isolation of human proteasomes and putative proteasome-interacting proteins using a novel affinity chromatography method.
    Experimental cell research, 2009, Jan-15, Volume: 315, Issue:2

    The proteasome is the primary subcellular organelle responsible for protein degradation. It is a dynamic assemblage of 34 core subunits and many differentially expressed, transiently interacting, modulatory proteins. This paper describes a novel affinity chromatography method for the purification of functional human holoproteasome complexes using mild conditions. Human proteasomes purified by this simple procedure maintained the ability to proteolytically process synthetic peptide substrates and degrade ubiquitinated parkin. Furthermore, the entire purification fraction was analyzed by mass spectrometry in order to identify proteasomal proteins and putative proteasome-interacting proteins. The mild purification conditions maintained transient physical interactions between holoproteasomes and a number of known modulatory proteins. In addition, several classes of putative interacting proteins co-purified with the proteasomes, including proteins with a role in the ubiquitin proteasome system for protein degradation or DNA repair. These results demonstrate the efficacy of using this affinity purification strategy for isolating functional human proteasomes and identifying proteins that may physically interact with human proteasomes.

    Topics: Adenosine Triphosphate; ATPases Associated with Diverse Cellular Activities; Binding Sites; Catalysis; Cell Line; Chromatography, Affinity; Coumarins; DNA Repair; DNA Repair Enzymes; DNA-Binding Proteins; Enzyme Stability; Humans; Leupeptins; Oligopeptides; Peptide Fragments; Proteasome Endopeptidase Complex; Protein Binding; Protein Subunits; Proteins; Tandem Mass Spectrometry; Ubiquitin; Ubiquitin-Activating Enzymes; Ubiquitin-Conjugating Enzymes; Ubiquitin-Protein Ligases

2009
Zn2+ mediates ischemia-induced impairment of the ubiquitin-proteasome system in the rat hippocampus.
    Journal of neurochemistry, 2009, Volume: 111, Issue:5

    Abstract Deposition of ubiquitinated protein aggregates is a hallmark of neurodegeneration in both acute neural injuries, such as stroke, and chronic conditions, such as Parkinson's disease, but the underlying mechanisms are poorly understood. In the present study, we examined the role of Zn2+ in ischemia-induced impairment of the ubiquitin-proteasome system in the CA1 region of rat hippocampus after transient global ischemia. We found that scavenging endogenous Zn2+ reduced ischemia-induced ubiquitin conjugation and free ubiquitin depletion. Furthermore, exposure to zinc chloride increased ubiquitination and inhibited proteasomal enzyme activity in cultured hippocampal neurons in a concentration- and time-dependent manner. Further studies of the underlying mechanisms showed that Zn(2+)-induced ubiquitination required p38 activation. These findings indicate that alterations in Zn2+ homeostasis impair the protein degradation pathway.

    Topics: Actins; Animals; CA1 Region, Hippocampal; Cells, Cultured; Chelating Agents; Coumarins; Disease Models, Animal; Dose-Response Relationship, Drug; Edetic Acid; Embryo, Mammalian; Enzyme Inhibitors; Fluorescent Dyes; Green Fluorescent Proteins; Imidazoles; Ischemia; Leupeptins; Male; Microtubule-Associated Proteins; Neurons; Oligopeptides; p38 Mitogen-Activated Protein Kinases; Proteasome Endopeptidase Complex; Pyrimidines; Rats; Rats, Sprague-Dawley; Statistics, Nonparametric; Time Factors; Transfection; Ubiquitin; Zinc

2009
Antioxidants block proteasome inhibitor function in endometrial carcinoma cells.
    Anti-cancer drugs, 2008, Volume: 19, Issue:2

    We have recently demonstrated that proteasome inhibitors can be effective in inducing apoptotic cell death in endometrial carcinoma cell lines and primary culture explants. Increasing evidence suggests that reactive oxygen species are responsible for proteasome inhibitor-induced cell killing. Antioxidants can thus block apoptosis (cell death) triggered by proteasome inhibition. Here, we have evaluated the effects of different antioxidants (edaravone and tiron) on endometrial carcinoma cells treated with aldehyde proteasome inhibitors (MG-132 or ALLN), the boronic acid-based proteasome inhibitor (bortezomib) and the epoxyketone, epoxomicin. We show that tiron specifically inhibited the cytotoxic effects of bortezomib, whereas edaravone inhibited cell death caused by aldehyde-based proteasome inhibitors. We have, however, found that edaravone completely inhibited accumulation of ubiquitin and proteasome activity decrease caused by MG-132 or ALLN, but not by bortezomib. Conversely, tiron inhibited the ubiquitin accumulation and proteasome activity decrease caused by bortezomib. These results suggest that edaravone and tiron rescue cells of proteasome inhibitors from cell death, by inhibiting blockade of proteasome caused by MG-132 and ALLN or bortezomib, respectively. We also tested other antioxidants, and we found that vitamin C inhibited bortezomib-induced cell death. Similar to tiron, vitamin C inhibited cell death by blocking the ability of bortezomib to inhibit the proteasome. Until now, all the antioxidants that blocked proteasome inhibitor-induced cell death also blocked the proteasome inhibitor mechanism of action.

    Topics: Antioxidants; Antipyrine; Apoptosis; Ascorbic Acid; Blotting, Western; Boronic Acids; Bortezomib; Butylated Hydroxyanisole; Caspase 3; Caspase 9; Caspase Inhibitors; Cell Line, Tumor; Cell Survival; Coumarins; Cysteine Proteinase Inhibitors; Dose-Response Relationship, Drug; Edaravone; Endometrial Neoplasms; Ergothioneine; Female; Humans; Leupeptins; Oligopeptides; Proteasome Inhibitors; Pyrazines; Ubiquitin; Vitamin E; Vitamins

2008
Schistosoma mansoni: functional proteasomes are required for development in the vertebrate host.
    Experimental parasitology, 2005, Volume: 109, Issue:4

    Proteasomes are multi-subunit proteases involved in several mechanisms and thought to contribute to the regulation of cellular homeostasis. Here, we report for the first time biochemical evidence for the existence of a ubiquitin-proteasome proteolytic pathway in this parasite. Proteasomes from both cercariae and adult worms exhibited a high preference for hydrolysis of the substrate Suc-LLVY-AMC, although in the cercariae extract the rate of hydrolysis was 50% lower when compared to adult worms extracts. The same difference in proteasome activities was observed when endogenous proteins were broken down in the presence of ATP and ubiquitin. Additionally, accumulation of high molecular weight conjugates was observed when cercariae were pre-incubated with proteasome inhibitors. Finally, we present evidence that during experimental schistosomiasis, proteasome inhibitors were able to reduce the number of lung stage schistosomula, reduce the worm burden and consequently decrease the egg output in infected mice.

    Topics: Adenosine Triphosphate; Animals; Biomphalaria; Coumarins; Host-Parasite Interactions; Hydrolysis; Leupeptins; Lung; Mice; Mice, Inbred BALB C; Oligopeptides; Protease Inhibitors; Proteasome Endopeptidase Complex; Proteasome Inhibitors; Schistosoma mansoni; Schistosomiasis mansoni; Ubiquitin

2005
Differential inhibition of calpain and proteasome activities by peptidyl aldehydes of di-leucine and tri-leucine.
    Journal of biochemistry, 1996, Volume: 119, Issue:3

    To explore membrane-permeable synthetic inhibitors that discriminate between endogenous calpain and proteasome in cells, we examined the inhibition of profiles against calpain and proteasome in vitro and in vivo of peptidyl aldehydes possessing di-leucine and tri-leucine. The tripeptide aldehyde benzyloxycarbonyl-leucyl-leucinal (ZLLLal) strongly inhibited calpain and proteasome activities in vitro. The concentration required for 50% inhibition (IC50) of the casein-degrading activity of calpain was 1.25 microM, and the IC50s for the succinyl-leucyl-leucyl-valyl-tyrosine-4-methylcoumaryl-7-amide (Suc-LLVY-MCA)- and benzyloxycarbonyl-leucyl-leucyl-leucine-4-methylcoumaryl -7-amide (ZLLL-MCA)-degrading activities of proteasome were 850 and 100 nM, respectively. On the other hand, the synthetic dipeptide aldehyde benzyloxycarbonyl-leucyl-leucinal (ZLLal) strongly inhibited the casein degrading activity of calpain (IC50 1.20 microM), but the inhibition of proteasome was weak (IC50S for SucLLVY-MCA- and ZLLL-MCA-degrading activities were 120 and 110 microM, respectively). Thus, while calpain was inhibited by similar concentrations of ZLLal and ZLLLal, the inhibitory potencies of ZLLLal against the ZLLL-MCA- and Suc-LLVY-MCA-degrading activities in proteasome were 1,100 and 140 times stronger than those of ZLLal, respectively. To evaluate the effectiveness of these inhibitors on intracellular proteasome, the induction of neurite outgrowth in PC12 cells caused by proteasome inhibition was examined. ZLLLal and ZLLal initiated neurite outgrowth with optimal concentrations of 20 nM and 10 microM, respectively, again showing a big difference in the effective concentrations for the proteasome inhibition as in vitro. As for the effect on intracellular calpain, the concentration of ZLLLal and ZLLal required for the inhibition of the autolytic activation of calpain in rabbit erythrocytes were 100 and 100 microM or more, respectively. The almost equal inhibitory potencies of ZLLLal and ZLLal were in agreement with the inhibition of calpain in vitro. These differential effects of inhibitors against calpain and proteasome are potentially useful for identifying the functions of calpain and proteasome in cell physiology and pathology.

    Topics: Animals; Autolysis; Calpain; Cattle; Coumarins; Cysteine Endopeptidases; Cysteine Proteinase Inhibitors; Enzyme Activation; Erythrocytes; Leupeptins; Microscopy, Phase-Contrast; Multienzyme Complexes; Neurites; Oligopeptides; PC12 Cells; Proteasome Endopeptidase Complex; Rabbits; Rats

1996
Isolation of two forms of the high-molecular-mass serine protease, ingensin, from porcine skeletal muscle.
    FEBS letters, 1985, Sep-09, Volume: 189, Issue:1

    Two forms of a neutral protease that catalyzed the hydrolysis of succinyl-Leu-Leu-Val-Tyr-MCA were isolated from porcine skeletal muscle cytosol by fractionation on DEAE-cellulose, hydroxyapatite and Sephadex G-100. The native enzyme had a molecular mass of above 1000 kDa. Peak A, which was eluted from hydroxyapatite at 50 mM phosphate, was activated 37-fold by the detergent, SDS, while peak B which was eluted at 150 mM phosphate, was activated only 2-fold. After dialysis against water, the B form showed restored ability to be activated by SDS (9.6-fold with 0.04% SDS). The activated peak B was extremely sensitive to divalent and monovalent cations such as Ca2+, Mg2+, Na+, K+ and NH+4 as well as protease inhibitors such as leupeptin, chymostatin and DFP. These results suggest that these proteases are generally latent in the cells and may be regulated by changes in the concentrations of cations in the cytosol. We call this new type of protease, ingensin.

    Topics: Animals; Antipain; Chromatography, DEAE-Cellulose; Chromatography, Gel; Chromatography, High Pressure Liquid; Coumarins; Cysteine Endopeptidases; Endopeptidases; Isoenzymes; Leucine; Leupeptins; Multienzyme Complexes; Muscles; Oligopeptides; Pepstatins; Proteasome Endopeptidase Complex; Sodium Dodecyl Sulfate; Swine

1985
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