benzyloxycarbonylleucyl-leucyl-leucine-aldehyde and herbimycin

benzyloxycarbonylleucyl-leucyl-leucine-aldehyde has been researched along with herbimycin* in 3 studies

Other Studies

3 other study(ies) available for benzyloxycarbonylleucyl-leucyl-leucine-aldehyde and herbimycin

ArticleYear
Participation of the human sperm proteasome in the capacitation process and its regulation by protein kinase A and tyrosine kinase.
    Biology of reproduction, 2009, Volume: 80, Issue:5

    The proteasome is a multicatalytic cellular complex present in human sperm that plays a significant role during several steps of mammalian fertilization. Here, we present evidence that the proteasome is involved in human sperm capacitation. Aliquots of highly motile sperm were incubated with proteasome inhibitors MG132 or epoxomicin. The percentage of capacitated sperm, the chymotrypsin-like activity of the proteasome, cAMP content, and the pattern of protein phosphorylation were assayed by using the chlortetracycline hydrochloride assay, a fluorogenic substrate, the cAMP enzyme immunoassay kit, and Western blot analysis, respectively. Our results indicate that treatment of sperm with proteasome inhibitors blocks the capacitation process, does not alter cAMP concentration, and changes the pattern of protein phosphorylation. To elucidate how proteasome activity is regulated during capacitation, sperm were incubated with: 1) tyrosine kinase (TK) inhibitors (genistein or herbimycin A); 2) protein kinase (PK) A inhibitors or activators (H89 and Rp-cAMPS, and 8-Br-cAMP, respectively); or 3) PKC inhibitors (tamoxifen or staurosporin) at different capacitation times. The chymotrypsin-like activity and degree of phosphorylation of the proteasome were then assayed. The results indicate that sperm treatment with TK and PKA inhibitors significantly decreases the chymotrypsin-like activity of the proteasome during capacitation. Immunoprecipitation and Western blot results suggest that the proteasome is phosphorylated during capacitation in a TK- and PKA-dependent pathway. In conclusion, we suggest that the sperm proteasome participates in the capacitation process, and that its activity is modulated by PKs.

    Topics: 8-Bromo Cyclic Adenosine Monophosphate; Benzoquinones; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Enzyme Activation; Enzyme Inhibitors; Genistein; Humans; In Vitro Techniques; Isoquinolines; Lactams, Macrocyclic; Leupeptins; Male; Oligopeptides; Phosphorylation; Proteasome Endopeptidase Complex; Proteasome Inhibitors; Protein-Tyrosine Kinases; Rifabutin; Sperm Capacitation; Spermatozoa; Sulfonamides; Thionucleotides

2009
A proteasome inhibitor confers cardioprotection.
    Cardiovascular research, 2002, Volume: 54, Issue:1

    In several cell types, proteasome inhibitors like carbobenzoxyl-leucinyl-leucinyl-leucinal (MG132) induce the 72 kDa heat shock protein (Hsp72) and exert cell protective effects. However, data in cardiomyocytes are currently lacking.. We investigated the effects of MG132 in cultured neonatal rat cardiomyocytes. MG132 time- and concentration-dependently induced Hsp72 and Hsp32 at mRNA and protein levels. Although Hsp60 mRNA was induced, Hsp60 protein levels were not altered. MG132 activated p38 MAP kinase already after 0.5 h. Hsp mRNA induction started after 2 h of MG132 treatment. Subsequently, Hsp72 and Hsp32 protein levels were increased after 4 h. SB202190, an inhibitor of p38 MAP kinase, concentration-dependently attenuated MG132-induced Hsp72-and Hsp32-elevations (by 59% and 41%, respectively, at 1 microM SB202190). In contrast, herbimycin A, a known inductor of Hsp72 in cardiomyocytes, enhanced the MG132-induced Hsp72 and Hsp32 expression even further: additionally applied 2 microM herbimycin A induced Hsp72 and Hsp32 about 2-fold higher than 1 microM MG132 alone. MG132 (1 microM) decreased the hyperthermia- or hydrogen peroxide-induced release of lactate dehydrogenase by 45% and by 35%, respectively (P<0.05, n=5). MG132 (1 microM) prolonged the spontaneous beating time of cardiomyocytes at 46 degrees C from 5+/-2 min (control hyperthermia) to 28+/-5 min (P<0.05, n=4). Thus, inhibition of the proteasome function by MG132 protects cardiomyocytes against hyperthermic or oxidative injury. This protective effect and Hsp induction were abolished by 1 microM SB202190.. Proteasome inhibition results in p38 MAP kinase-dependent induction of Hsp72 and Hsp32 and might be a novel cardioprotective modality.

    Topics: Animals; Benzoquinones; Blotting, Western; Cells, Cultured; Cysteine Proteinase Inhibitors; Dose-Response Relationship, Drug; Enzyme Inhibitors; Fever; Heat-Shock Proteins; Heme Oxygenase (Decyclizing); Heme Oxygenase-1; HSP72 Heat-Shock Proteins; Imidazoles; In Vitro Techniques; Lactams, Macrocyclic; Leupeptins; Mitogen-Activated Protein Kinases; Myocardium; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Papillary Muscles; Pyridines; Quinones; Rats; Rats, Sprague-Dawley; Rifabutin; RNA, Messenger

2002
Transient nuclear factor kappaB (NF-kappaB) activation stimulated by interleukin-1beta may be partly dependent on proteasome activity, but not phosphorylation and ubiquitination of the IkappaBalpha molecule, in C6 glioma cells. Regulation of NF-kappaB lin
    The Journal of biological chemistry, 1999, May-28, Volume: 274, Issue:22

    We previously reported that several stresses can induce cytokine-induced neutrophil chemoattractant expression in a nuclear factor kappaB (NF-kappaB)-dependent manner. In this study, we focused further on the regulation of NF-kappaB. The activation of NF-kappaB and the subsequent cytokine-induced neutrophil chemoattractant induction in response to interleukin-1beta (IL-1beta) were inhibited by proteasome inhibitors, MG132 and proteasome inhibitor I. Translocation of NF-kappaB into nuclei occurs by the phosphorylation, multi-ubiquitination, and degradation of IkappaBalpha, a regulatory protein of NF-kappaB. Nascent IkappaBalpha began to degrade 5 min after treatment with IL-1beta and disappeared completely after 15 min. However, IkappaBalpha returned to basal levels after 45-60 min. Interestingly, resynthesized IkappaBalpha was already phosphorylated at Ser-32. These results suggest that 1) the upstream signals are still activated, although the translocation of NF-kappaB peaks at 15 min; and 2) the regulated protein(s) acts downstream of IkappaBalpha phosphorylation. Western blotting showed that the resynthesized and phosphorylated IkappaB molecules were also upward-shifted by multi-ubiquitination in response to IL-1beta treatment. On the other hand, ATP-dependent Leu-Leu-Val-Tyr cleaving activity transiently increased, peaked at 15 min, and then decreased to basal levels at 60 min. Furthermore, the cytosolic fraction that was stimulated by IL-1beta for 15 min, but not for 0 and 60 min, could degrade phosphorylated and multi-ubiquitinated IkappaBalpha. These results indicate that the transient translocation of NF-kappaB in response to IL-1beta may be partly dependent on transient proteasome activation.

    Topics: Animals; Benzoquinones; Chemokines, CXC; Chemotactic Factors; Cysteine Endopeptidases; DNA-Binding Proteins; Enzyme Activation; Gene Expression Regulation; Glioma; Growth Substances; I-kappa B Proteins; Intercellular Signaling Peptides and Proteins; Interleukin-1; Lactams, Macrocyclic; Leupeptins; Multienzyme Complexes; NF-kappa B; NF-KappaB Inhibitor alpha; Oligopeptides; Phosphorylation; Protease Inhibitors; Proteasome Endopeptidase Complex; Quinones; Rats; Rifabutin; RNA, Messenger; Transcriptional Activation; Tumor Cells, Cultured; Ubiquitins

1999
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