Disease relevance of TOSYLLYSINE CHLOROMETHYL KETONE

• In hepatoma 7777, TLCK (2.5 mg/100 g body wt) exerted a greater inhibitory effect on incorporation when administered 60 minutes before [3H]leucine injection than when injected simultaneously [1].
• In the present study we evaluated the effect of TLCK or TPCK treatment on the immortalization of primary keratinocytes by transfected HPV-18 DNA [2].
• Pre-incubation with the NFkappaB pathway inhibitors, N-alpha-tosyl-L-lysine chloromethyl ketone (TLCK) or pyrrolidine dithiocarbamate (PDTC), or infection with adenovirus encoding IkappaBalpha, blocked both IRF-1 induction and NFkappaB DNA-binding activity [3].
• The protection from soman toxicity by chemically distinct protease inhibitors such as suramin and TLCK suggests a role for pathological proteolytic pathways in soman intoxication [4].
• Tosyl-L-lysine chloromethyl ketone (TLCK) and pentamidine isethionate, potent trypsin inhibitors, also dose-dependently inhibited the growth of E. coli and the DNA synthesis [5].

High impact information on TOSYLLYSINE CHLOROMETHYL KETONE

• Furthermore, SNP and GSNO as well as PDTC and TLCK significantly increased the cytoplasmic level of IkappaBalpha [6].
• TLCK treatment had no effect on Fas expression levels on the cell surface, and neither promoted death-inducing signaling complex formation nor decreased expression levels of cellular inhibitors of apoptosis (FLICE inhibitory protein, X chromosome-linked inhibitor of apoptosis, and Bcl-2) [7].
• The enhancing effect of TLCK is specific to Fas-induced cell death, with no effect seen on TNF-alpha or TNF-related apoptosis-inducing ligand-induced apoptosis [7].
• We found that a serine protease inhibitor, N-tosyl-L-lysine chloromethyl ketone (TLCK), dramatically enhances Fas-mediated apoptosis in the human T cell line Jurkat and in various B cell lines resistant to Fas-mediated apoptosis [7].
• IFN-gamma/LPS-induced NO production from murine peritoneal macrophages was inhibited by TPCK and TLCK in a dose-dependent manner (EC50s: approximately 20 microM for TPCK and approximately 30 microM for TLCK) [8].

Chemical compound and disease context of TOSYLLYSINE CHLOROMETHYL KETONE

• Ethanol-induced apoptosis in hepatoma cells proceeds via intracellular Ca(2+) elevation, activation of TLCK-sensitive proteases, and cytochrome c release [9].

Biological context of TOSYLLYSINE CHLOROMETHYL KETONE

• The effect of TLCK on transcription and its role in modifying cell growth [10].
• Kinetics of TLCK-mediated inhibition of cytadherence of other T. vaginalis isolates with different levels of epithelial-cell parasitism were similar to the concentration-dependent inhibition seen for isolate NYH 286 [11].
• The Tos-Lys-CH2Cl or Tos-Phe-CH2Cl treatment does not change the membrane IgM density as measured by flow cytometry, indicating that the active site of the inhibitors is distal to the membrane IgM molecule [12].
• Involvement of TLCK-sensitive serine protease in colchicine-induced cell death of sympathetic neurons in culture [13].
• TPCK and TLCK, when added after PMA, accelerated the return to basal rates of both oxygen consumption and superoxide production [14].

Anatomical context of TOSYLLYSINE CHLOROMETHYL KETONE

• The kinase activity of T cell plasma membrane fractions was inhibited by TLCK; the B cell activity was unaffected [15].
• Effects of N alpha-tosyl-L-lysyl-chloromethylketone on the activity of cytotoxic T lymphocytes [16].
• EGTA and TLCK could inhibit cytochrome c release from the mitochondria [9].
• Prior treatment of the W50 culture supernatant with the protease inhibitor Nalpha-p-tosyl-L-lysine chloromethyl ketone (TLCK) blocked its effects on cultured cells, indicating that this process is proteolytically mediated [17].
• The synthetic protease inhibitor N-tosyl-L-lysine-chloromethyl ketone (TLCK) acts to inhibit transcription when added to cell lines growing in vitro [10].

Associations of TOSYLLYSINE CHLOROMETHYL KETONE with other chemical compounds

• The protease inhibitors N alpha-tosylphenylalanyl chloromethyl ketone (TPCK) and N alpha-tosyl-L-lysine chloromethyl ketone (TLCK) block activation of NF-kappa B/Rel proteins by preventing degradation of I kappa B alpha [18].
• PMSF, diisopropylfluorophosphate, and N alpha-tosyl-L-lysyl-chloromethylketone were, again, inhibiting Fc gamma RII-mediated binding dose-dependently, whereas several inhibitors of metal, aspartic, or thiol proteases proved ineffective [19].
• Incubation of CEM cells with N alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK) indicates that ETS proteins can be modified in their cellular context and that pretreatment of the cells with N-ethylmaleimide (NEM) protects ETS1 proteins from TLCK modification [20].
• Moreover, the enzymatic activity(ies) in T. denticola responsible for glutathione breakdown was inactivated by trypsin or proteinase K, by heating (56 degrees C) and freezing (-20 degrees C), by sonication, and by exposure to N alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK) [21].
• Site-specific mutagenesis demonstrated that the E7 Rb-binding core (Leu-X-Cys-X-Glu) contained a cysteine residue which was essential for this modification and that the TLCK/TPCK-dependent alteration of the E7 protein abolished its ability to bind Rb [22].

Gene context of TOSYLLYSINE CHLOROMETHYL KETONE

• The TNF stimulated A549 cell culture supernatant had significantly (P < 0.05) greater chemotactic ability than control supernatant, while aprotinin and TLCK significantly (P < 0.05) reduced this chemotactic ability [23].
• Pyrrolidine dithiocarbamate (PDTC) and N-alpha-tosyl-L-lysine chloromethyl ketone (TLCK), two inhibitors of NF-kappaB activation, as well as the specific proteasome inhibitor MG132, blocked leptin-induced iNOS [24].
• Inhibitors of I-kappaB degradation, MG132 and N(alpha)-p-tosyl-L-lysine chloromethyl ketone (TLCK), suppressed the further increase by gamma-irradiation in IFN-gamma-induced NO production, showing that gamma-irradiation induced NO production via NF-kappaB activation [25].
• Induction of COX-2 activity along with the induction of COX-2 mRNA and protein by LPS was attenuated by the serine protease inhibitors N-alpha-tosyl-L-phenylalanine chloromethyl ketone (TPCK) and N-alpha-tosyl-L-lysine chloromethyl ketone (TLCK) [26].
• The ETS1.PEA3 complex formed with TLCK-modified ETS1 has a slower mobility than the complex formed with unmodified ETS1 [20].

Analytical, diagnostic and therapeutic context of TOSYLLYSINE CHLOROMETHYL KETONE

• The rAd effect correlated with a rapid increase (1 h) in the NF-kappaB-DNA binding activity detected by electrophoretic mobility shift assays. rAd-induced DC maturation was blocked by the proteasome inhibitor Nalpha-p-tosyl-L-lysine chloromethyl ketone (TLCK) or by infection with rAd-IkappaB, an rAd-encoding the dominant-negative form of IkappaB [27].
• RESULTS: TLCK prolonged hepatic allograft survival [28].
• Thrombin inactivated with Tos-Lys-CH2Cl also showed two peaks of radioactivity on gel filtration, one peak which was excluded from the column and the other peak with an elution volume that was consistent with the position of native thrombin [29].
• In vitro, TLCK suppressed interleukin-2 production and [(3)H]thymidine incorporation into an allogeneic mixed lymphocyte reaction [28].
• Preincubation of eggs before fertilization with 100 microM TPCK, but not TLCK, resulted in inhibition of fertilization [30].

References