The effect of analogues of chymostatin on lysosomal and non-lysosomal components of protein degradation in isolated hepatocytes☆

Place, Graham A.; Chetland, Janet; Galpin, I.J.; Beynon, Robert J.

doi:10.1016/0304-4165(87)90108-5

Cited by 7 publications

(7 citation statements)

References 16 publications

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“…It is of interest that a similar increase in Ang II production from Ang I was detected in the cells of SHR versus WKY rats, as well as in RVCH versus vector-transfected A10 cells, and could be attributed to chymase activity, i.e., in that it was chymostatin inhibitable. It has been shown in hepatocytes (63,64) and in cancer cells (65) that chymostatin can enter cells and inhibit intracellular proteolysis, and chymase inhibitors can also inhibit enzymes associated with the cell membrane (66). Recent studies have…”

Section: Discussionmentioning

confidence: 99%

A novel vascular smooth muscle chymase is upregulated in hypertensive rats

Guo¹,

Ju²,

Leung³

et al. 2001

J. Clin. Invest.

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Section: Discussionmentioning

confidence: 99%

A novel vascular smooth muscle chymase is upregulated in hypertensive rats

Guo¹,

Ju²,

Leung³

et al. 2001

J. Clin. Invest.

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“…Two synthetic chymostatin analogues containing a phenylalanine aldehyde (Z-Arg-VaI-Phe-CHO) or a semicarbazone (Z-Arg-Leu-Phe-CH=N .NH-CONH2) reactive function respectively (Place et al, 1987) were generous gifts from Dr R. J. Beynon, University of Liverpool, U.K. Recombinant human cystatin C (Abrahamson et al, 1988) was kindly provided by Dr M. Abrahamson, Maim6 General Hospital, Sweden.…”

Section: Methodsmentioning

confidence: 99%

“…E64, an epoxysuccinyl peptide shown to inactivate rapidly several cysteine proteinases, including ficin, papain, cathepsin B and stem bromelains (Barrett et al, 1982;Elliott & Liu, 1970;Rich, 1986), did not inhibit the viral proteinase. However, another peptide aldehyde, chymostatin, an inhibitor of chymotrypsinqike enzymes (Place et al, 1987;Powers & Harper, 1986b), was found to be a competitive inhibitor of the HRV 3C proteinase, albeit not a particularly good one. Two synthetic chymotrypsin analogues, Z-Arg-Val-PheH and Z-Arg-Leu-PheSc (Place et al, 1987), were also tested, but were found to possess no inhibitory activity.…”

Section: Effects Of General Proteinase Inhibitors On the Cleavage Of mentioning

confidence: 99%

“…However, another peptide aldehyde, chymostatin, an inhibitor of chymotrypsinqike enzymes (Place et al, 1987;Powers & Harper, 1986b), was found to be a competitive inhibitor of the HRV 3C proteinase, albeit not a particularly good one. Two synthetic chymotrypsin analogues, Z-Arg-Val-PheH and Z-Arg-Leu-PheSc (Place et al, 1987), were also tested, but were found to possess no inhibitory activity. Other serine proteinase inhibitors (NCDC, aprotinin, elastatinal, APMSF and PMSF) (Powers & Harper, 1986b) and metalloproteinase inhibitors (bestatin, amastatin, epiamastatin and phosphoramidon) (Powers & Harper, 1986a) also all failed to show any activity against the HRV-14 3C proteinase.…”

Section: Effects Of General Proteinase Inhibitors On the Cleavage Of mentioning

confidence: 99%

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Hydrolysis of a Series of Synthetic Peptide Substrates by the Human Rhinovirus 14 3C Proteinase, Cloned and Expressed in Escherichia coli

Orr¹,

Long²,

Kay³

et al. 1989

Journal of General Virology

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SUMMARYThe 3C proteins of several picornaviruses, including poliovirus, foot-and-mouth disease virus (FMDV) and encephatomyocarditis virus (EMCV), have been demonstrated to be cysteine-type proteinases, involved in the processing of the respective polyproteins expressed by the monocistronic RNA genome. Nucleotide sequencing data have indicated that the human rhinovirus 14 (HRV-14) RNA genome encodes a homologous 3C protein. The HRV-14 3C protein was purified to homogeneity from Escherichia coli expressing the cloned 3C genomic fragment. The enzyme was assayed against peptides corresponding to those residues, predicted (by nucleotide sequencing data) to occur at authentic cleavage sites within the polyprotein. The peptides representing the 1B/1C, 2A/2B, 2C/3A, 3A/3B, 3B/3C and 3C/3D cleavage sites, where proteolysis was predicted to occur at a Gln-Gly junction, were all cleaved by the 3C proteinase. The hydrolysis was shown (by reverse phase fast protein liquid chromatography and amino acid analysis) to occur specifically at the Gln-Gly bond in each of the peptides. The ready availability of such convenient substrates facilitated the further characterization of the 3C proteinase. By contrast, peptides corresponding to the predicted 2B/2C and 1C/1D cleavage sites, where the processing was presumed to occur at a Gln-Ala or Glu-Gly bond respectively, were not cleaved by the 3C proteinase. The ability of the HRV-14 3C proteinase to hydrolyse the synthetic peptides was inhibited if a Cys~Ser(146) mutation was introduced into the protein. Studies with known proteinase inhibitors substantiated the conclusion that the HRV-14 3C protein appears to be a cysteine proteinase and that the Cys residue at position 146 may be the active site nucleophile. The HRV-14 3C proteinase probably plays an important role, analogous to that implied for the poliovirus 3C proteinase, in the replication of the virus and thus represents a potential target for antiviral chemotherapy.

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“…Chymostatin and some of chymostatin analogues (Place et al, 1987) were tested as inhibitors of the various proteolytic activities of the MCP complex. Such compounds might be expected to inhibit only the chymotrypsin-like activity.…”

Section: Inhibition By Chymostatin Analoguesmentioning

confidence: 99%

Use of serine‐protease inhibitors as probes for the different proteolytic activities of the rat liver multicatalytic proteinase complex

Djaballah

Harness

Savory

et al. 1992

European Journal of Biochemistry

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The multicatalytic proteinase (MCP) complex catalyses cleavage of bonds on the carboxy-group side of basic, hydrophobic or acidic amino acid residues. Orginally, it was proposed that the complex contained three distinct types of catalytic component. MCP from rat liver has been assayed for socalled trypsin-like activity with Boc-Leu-Ser-Thr-Arg-NH-Mec (Mec, 4-methylcoumarin; Boc, tbutoxycarbonyl), for chymotrypsin-like activity with Ala-Ala-Phe-NH-Mec and Suc-Leu-Leu-ValTyr-NH-MEc (SUC, succinyl), and peptidyl-glutamylpeptide hydrolase activity with Cbz-Leu-LeuGlu-Nap (Nap, naphthylamide; Cbz, benzyloxycarbonyl). Results of these studies suggest that as many as five distinct components can be distinguished, one for the trypsin-like activity and two for each of the others. The activities were tested with a variety of serine-protease inhibitors, and other novel effectors have also been identified. The two most effective inhibitors were 4-(2-aminoethy1)benzenesulphonyl fluoride, which selectivity inactivates the trypsin-like activity, and 3,4-dichloroisocoumarin which inhibits chymotrypsin-like activity and the second, cooperative component [Djaballah, H. & Rivett, A. J. (1992) Biochemistry 31, 4133 -41411 of peptidylglutamylpeptide hydrolase activity. Thc three activities inhibited by 3,4-dichloroisocoumarin can easily be distinguished by the effects of chyrnostatin analogues, diisopropylfluorophosphate, guanidine/HCl and casein. The results support the view that the enzyme is a novel type of serine protease and suggest that it may contain at least five distinct catalytic components. Marked differences in the reactivities of the different catalytic sites with different reagents can be used to distinguish between them.

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The effect of analogues of chymostatin on lysosomal and non-lysosomal components of protein degradation in isolated hepatocytes☆

Cited by 7 publications

References 16 publications

A novel vascular smooth muscle chymase is upregulated in hypertensive rats

A novel vascular smooth muscle chymase is upregulated in hypertensive rats

Hydrolysis of a Series of Synthetic Peptide Substrates by the Human Rhinovirus 14 3C Proteinase, Cloned and Expressed in Escherichia coli

Use of serine‐protease inhibitors as probes for the different proteolytic activities of the rat liver multicatalytic proteinase complex

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