Proteolytic processing inhibition

As shown in Table I, free HRP is poorly transported across MDCK cells but, when conjugated to a PLL carrier, HRP transport is increased considerably. The existence of a proteolytic compartment involved in the transcytotic digestion of HRP-S-PLL conjugate was further confirmed by the finding that when PLL was replaced by PDL, the transport of HRP was completely abolished (Table I) (8). In addition, when protease inhibitors such as leupeptin were added to the basal medium, the transcytosis of HRP was also significantly decreased (Table I). We have previously reported that the partial degradation of HRP-S-PLL was not inhibited by lysosomotropic amines (<8), indicating that this proteolytic process does not occur in lysosomes. 

Stehlik C, de Martin R, Kumabashiri I, Schmid JA, Binder BR, Lipp J (1998) Nuclear factor (NF)-kappaB-regulated X-chromosome-linked iap gene expression protects endothelial cells from tumor necrosis factor alpha-induced apoptosis. J Exp Med 188 211-216 Stennicke HR, Deveraux QL, Humke EW, Reed JC, Dixit VM, Salvesen GS (1999) Caspase-9 ctin be activated without proteolytic processing. J Biol Chem 274 8359-8362 Sun XM, Butterworth M, MacFarlane M, Dubiel W, Ciechanover A, Cohen GM (2004) Caspase activation inhibits proteasome function during apoptosis. Mol Cell 14 81-93 Suzuki Y, Imai Y, Nakayama H, Takahashi K, Takio K, Takahashi R (2001) A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death. Mol Cell 8 613-621... 

D. Pan and G. M. Rubin. Kuzhanian controls proteolytic processing of Notch and mediates lateral inhibition during DrosophUa and vertebrate neurogenesis. Cell, 90 (2), 271—280, 1997. 

The potato metallocarboxypeptidase inhibitor (and metallo-carboxypeptidase inhibitors from leeches and ticks) inhibit car-boxypeptidase B after a proteolytic processing event. These... 

Pan, D. and Rubin, J. (1997). KUZBANIAN controls proteolytic processing of NOTCH and mediates lateral inhibition during Drosophila and vertebrate neurogenesis. Cell 90 271-280. 

None of the protein inhibitors of NE presented in this chapter are protease specific. They all inhibit more than one protease, but they are protease class specific (Table 5). For example, ai-PI, SLPI, and eglin c are serine-protease inhibitors and inhibit trypsin, chymotrypsin, and cathepsin G in addition to NE. However, ai-PI is an inhibitor of neutrophil PR3, whereas SLPI and eglin c are only very weak inhibitors of PR3 [40]. By contrast, elafin, which shares 38% homology with the C-terminal domain of SLPI, does inhibit PR3. A strong selectivity for NE is important to reduce toxicity resulting from interference of the inhibitor with other proteolytic processes. 

Regulation of MMP activity is quite complex. These regulatory processes include transcriptional regulation, proteolytic activation, inhibition by the circulating protein a2-macroglobulin, and regulation by a class of inhibitors known as... 

Epigallocatechin-3-gallate Camellia sinensis L.) reduces cleavage of APP and A(3 formation in murine neuroblastoma cells (N2a) transfected with the human Swedish mutant APP. It also inhibits production of A(3 in primary neurons (Tg2576) by support of proteolytic process by a-secretase, increasing... 

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