Inhibition of calpain in intact platelets by the thiol protease inhibitor E-64d

McGowan, Eleanor B.; Becker, Edward J.; Detwiler, Thomas C.

doi:10.1016/s0006-291x(89)80065-8

Cited by 102 publications

(49 citation statements)

References 8 publications

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“…To distinguish between these proteases, and to emphasize the importance of the proteasome, several additional inhibitors were applied: PSI, which is one of the most potent proteasome inhibitors currently available [32] as well as the calpain inhibitors E64 [26,41], E64d [42][43][44], and calpeptin [42,45,46]. Our data demonstrated that in the presence of PSI (Fig.…”

Section: Proteasome Inhibitors Prevent Activation-induced Depletion Omentioning

confidence: 81%

“…Using PSI, a relatively specific inhibitor for the proteasome [32], and several calpain inhibitors which do not or only weakly affect the proteasome [26,[41][42][43][44][45][46], we were able to distinguish between these proteases. Thus, our data strongly indicate an important role for the proteasome in the regulation of monocytic cytokine expression.…”

Section: Discussionmentioning

confidence: 99%

“…Moroder,personal communication]; N-benzyloxycarbonyl-Ile-Glu-(O-t-Bu)-Ala-leucinal (PSI, Peptide Institute Inc., Osaka, Japan), one of the most potent proteasome inhibitors available [32]; and the calpain inhibitors E64, E64d (Sigma), and calpeptin (Calbiochem-Novabiochem, Bad Soden, Germany) [26,[41][42][43][44][45][46]. Inhibitors were added to cell cultures 1 h before LPS stimulation.…”

Section: Inhibitorsmentioning

confidence: 99%

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Effect of proteasome inhibitors on monocytic IκB-α and -β depletion, NF-κB activation, and cytokine production

Haas

Page

et al. 1998

Journal of Leukocyte Biology

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Abstract:We investigated the effect of proteasome inhibitors on the lipopolysaccharide (LPS)-induced expression of several monocytic cytokines, which may be dependent on the transcription factor, nuclear factor-B (NF-B). Exposure of human monocytic THP-1 cells to ALLN and Mu873 prevented the LPS-induced degradation of I B-␣ and -␤, as did the more potent proteasome inhibitor, PSI, whereas several calpain inhibitors were ineffective. This was accompanied by the inhibition of nuclear NF-B binding activity and NF-B transcriptional activation. At the mRNA level, the inhibitors blocked the expression of tumor necrosis factor (TNF) and interleukin-1␤ (IL-1␤), whereas IL-8 remained unaffected by ALLN and was only partially reduced by the highest dose of PSI. The latter effect appears to be due to an increase in IL-8 mRNA stability in the presence of proteasome inhibitors. Furthermore, the production of TNF was efficiently suppressed by ALLN and PSI, less by Mu873, and not at all by calpain inhibitors. In primary human blood monocytes ALLN also prevented the LPS-induced degradation of I B-␣ and -␤, efficiently blocked the production of TNF and, to a lesser extent, IL-1␤, whereas that of IL-8 was not inhibited. The expression of NF-B-dependent monocytic cytokines may be selectively controlled by the proteasome, offering a potential therapeutic target in inflammatory disease.

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Section: Proteasome Inhibitors Prevent Activation-induced Depletion Omentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Inhibitorsmentioning

confidence: 99%

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Effect of proteasome inhibitors on monocytic IκB-α and -β depletion, NF-κB activation, and cytokine production

Haas

Page

et al. 1998

Journal of Leukocyte Biology

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“…2A inset). The specific role of proteasome inhibition in the upregulation of TNF-α release is reinforced by the fact that lactacystin was also able to increase the release of TNF-α, whereas E-64d, a membrane permeable inhibitor of lysosomal cysteine proteases (McGowan et al, 1989), was without effect (Fig. 2B).…”

Section: Proteasome Inhibition Increases the Release Of Tnfrsmentioning

confidence: 95%

Proteasome inhibition activates the transport and the ectodomain shedding of TNF-α receptors in human endothelial cells

Peiretti

Canault

Bernot

et al. 2005

Journal of Cell Science

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Binding of tumor necrosis factor-α (TNF-α) to its transmembrane receptors (TNFRs) mediates proinflammatory, apoptotic and survival responses in several cell types including vascular endothelial cells. Because ectodomain shedding of cell surface molecules can be modified by proteasome activity, we studied in human endothelial cells whether the TNF-α–TNFRs axis can be regulated by the cleavage of their transmembrane forms in a proteasome-dependent manner. We show that proteasome inhibition increases the release of TNF-α and TNFRs from human endothelial cells and decreases their cellular and cell surface expression. This phenomenon involves the transient activation of mitogen-activated protein kinase p42/p44 that triggers the dispersion of TNF-α and TNFRs from their intracellular Golgi-complex-associated pool towards the plasma membrane. This results in their enhanced cleavage by TNF-α converting enzyme (TACE) because it is reduced by synthetic metalloprotease inhibitors, recombinant TIMP-3 and by a dominant negative form of TACE. In the presence of TACE inhibitor, proteasome inhibition increases the cell surface expression of TNFRs and enhances the sensitivity of these cells to the proapoptotic effect of recombinant TNF-α. In conclusion, our data provide evidence that proteasome inhibitors increase TACE-dependent TNFR-shedding in endothelial cells, supporting the use of these molecules in inflammatory disorders. In association with TACE inhibitor, proteasome inhibitors increase the amount of TNFRs at the cell surface and enhance the sensitivity to the proapoptotic effect of TNF-α, which might be of interest in the antitumor therapy.

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“…The cells were treated with KCM only, with 100 mg/ml of EMD or pre-treated for 10 min with 20 mM E64d [(2S,3S)-trans-epoxysuccinyl-Lleucylamido-3-methylbutane ethyl ester; inhibits lysosomal degradation of endocytosed proteins (McGowan et al, 1989)], followed by addition of 100 mg/ ml of EMD. The cells were then incubated for 24 h and processed for immunofluorescence staining with anti-amelogenin antibody (PC-062).…”

Section: Amelogenin Endocytosis By Ameloblast-like Cellsmentioning

confidence: 99%

Critical role for αvβ6 integrin in enamel biomineralization

Mohazab

Koivisto

Jiang

et al. 2012

Journal of Cell Science

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SummaryTooth enamel has the highest degree of biomineralization of all vertebrate hard tissues. During the secretory stage of enamel formation, ameloblasts deposit an extracellular matrix that is in direct contact with the ameloblast plasma membrane. Although it is known that integrins mediate cell-matrix adhesion and regulate cell signaling in most cell types, the receptors that regulate ameloblast adhesion and matrix production are not well characterized. We hypothesized that avb6 integrin is expressed in ameloblasts where it regulates biomineralization of enamel. Human and mouse ameloblasts were found to express both b6 integrin mRNA and protein. The maxillary incisors of Itgb6 2/2 mice lacked yellow pigment and their mandibular incisors appeared chalky and rounded. Molars of Itgb6 2/2 mice showed signs of reduced mineralization and severe attrition. The mineral-to-protein ratio in the incisors was significantly reduced in Itgb6 2/2 enamel, mimicking hypomineralized amelogenesis imperfecta. Interestingly, amelogenin-rich extracellular matrix abnormally accumulated between the ameloblast layer of Itgb6 2/2 mouse incisors and the forming enamel surface, and also between ameloblasts. This accumulation was related to increased synthesis of amelogenin, rather than to reduced removal of the matrix proteins. This was confirmed in cultured ameloblast-like cells, in which avb6 integrin was not an endocytosis receptor for amelogenins, although it participated in cell adhesion on this matrix indirectly via endogenously produced matrix proteins. In summary, integrin avb6 is expressed by ameloblasts and it plays a crucial role in regulating amelogenin deposition and/or turnover and subsequent enamel biomineralization.

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Inhibition of calpain in intact platelets by the thiol protease inhibitor E-64d

Cited by 102 publications

References 8 publications

Effect of proteasome inhibitors on monocytic IκB-α and -β depletion, NF-κB activation, and cytokine production

Effect of proteasome inhibitors on monocytic IκB-α and -β depletion, NF-κB activation, and cytokine production

Proteasome inhibition activates the transport and the ectodomain shedding of TNF-α receptors in human endothelial cells

Critical role for αvβ6 integrin in enamel biomineralization

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