Assessment of circulating proteasome chymotrypsin-like activity in plasma of patients with acute and chronic leukemias

Ostrowska, H; Hempel, Dominika; Holub, M.; Sokołowski, Jarosław; Kłoczko, Janusz

doi:10.1016/j.clinbiochem.2008.08.063

Cited by 22 publications

(20 citation statements)

References 26 publications

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“…Moreover, latest findings indicate the clinical relevance of the plasma proteasome ChT-L activity in patients with chronic lymphocytic leukemia [17], advanced-stage myelodysplastic syndrome, and acute myeloid leukemia [18,19]. We have also reported that plasma proteasome ChT-L activity can be a useful biomarker in patients with acute myeloblastic leukemia and acute lymphoblastic leukemia [20].…”

Section: Introductionmentioning

confidence: 92%

Increased plasma proteasome chymotrypsin-like activity in patients with advanced solid tumors

et al. 2011

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The chymotrypsin-like (ChT-L) activity is one of the key regulators of intracellular protein degradation. Elevated proteasome ChT-L activity has recently been reported in plasma of patients with leukemia and myelodysplastic syndrome and suggested to have a prognostic significance. The aim of the present study was to evaluate plasma proteasome ChT-L activity in patients with newly diagnosed solid tumors at early and advanced stages of the disease. The activity was assayed using the fluorogenic peptide substrate, Suc-Leu-Leu-Val-Tyr-AMC, in a cohort of 155 patients with early/advanced rectal (n=43/29), gastric (n=6/13), and breast (n=37/27) cancer and compared with that in normal individuals (n=55). The median plasma proteasome ChT-L activity was elevated by 20-32% in patients with advanced stage of rectal, gastric, and breast cancer compared with healthy donors. The difference turned out to be statistically significant (P<0.001). By contrast, values in patients with early stage of malignancies were not significantly different from those observed in normal individuals. We also found that plasma proteasome activity correlated with serum carcinoembryonic antigen levels in the group of patients with rectal cancer (r=0.433, P<0.05). Elevated plasma proteasome ChT-L activity is indicative of advanced stage of rectal, gastric, and breast cancer. However, the activity does not seem to be a parameter with clinically relevant potential in terms of early detection of cancer in this subset of patients.

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Section: Introductionmentioning

confidence: 92%

Increased plasma proteasome chymotrypsin-like activity in patients with advanced solid tumors

et al. 2011

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“…We speculate that in the serum samples, the majority of the peptides were processed by a protease(s) of unknown serum origin that was not inhibited by an effective dose of carfilzomib (10 nM). Indeed, serum is a rich source of proteolytic enzymes [36]. Only a small percentage of peptide 1 was processed by the proteasome, as judged by its proteolytic pattern and MS analysis.…”

Section: Discussionmentioning

confidence: 99%

Bladder cancer detection using a peptide substrate of the 20S proteasome

et al. 2016

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The 20S catalytic core of the human 26S proteasome can be secreted from cells, and high levels of extracellular 20S proteasome have been linked to many types of cancers and autoimmune diseases. Several diagnostic approaches have been developed that detect 20S proteasome activity in plasma, but these suffer from problems with efficiency and sensitivity. In this report, we describe the optimization and synthesis of an internally quenched fluorescent substrate of the 20S proteasome, and investigate its use as a potential diagnostic test in bladder cancer. This peptide, 2‐aminobenzoic acid (ABZ)‐Val‐Val‐Ser‐Tyr‐Ala‐Met‐Gly‐Tyr(3‐NO2)‐NH2, is cleaved by the chymotrypsin 20S proteasome subunit and displays an excellent specificity constant value (9.7 × 105 m−1·s−1) and a high kcat (8 s−1). Using this peptide, we identified chymotrypsin‐like proteasome activity in the majority of urine samples obtained from patients with bladder cancer, whereas the proteasome activity in urine samples from healthy volunteers was below the detection limit (0.5 pm). These findings were confirmed by an inhibitory study and immunochemistry methods.

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“…It may be possible to determine the proteoltyic or other enzymatic activities in the sample on the basis of mass spectral observations (Marshall et al, 2003de Souza, Godoy, & Mann, 2006). A proteasomal chymotrypsinlike activity was assayed using a fluorogenic peptide substrate and showed an increase in plasma of patients with acute lymphoblastic, acute myeloblastic, and chronic lymphocytic leukemias (Ostrowska et al, 2008). There have been equivocal results in the application of the glycoprofile of tissue inhibitor of metalloproteinase-1 towards cancer screening (Zhou et al, 1998;Nicol et al, 2008;Thaysen-Andersen et al, 2008).…”

Section: Mass Spectrometry Of Bloodmentioning

confidence: 99%

Mass spectrometry of peptides and proteins from human blood

Zhu

Bowden

Zhang

et al. 2010

Mass Spectrometry Reviews

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It is difficult to convey the accelerating rate and growing importance of mass spectrometry applications to human blood proteins and peptides. Mass spectrometry can rapidly detect and identify the ionizable peptides from the proteins in a simple mixture and reveal many of their post-translational modifications. However, blood is a complex mixture that may contain many proteins first expressed in cells and tissues. The complete analysis of blood proteins is a daunting task that will rely on a wide range of disciplines from physics, chemistry, biochemistry, genetics, electromagnetic instrumentation, mathematics and computation. Therefore the comprehensive discovery and analysis of blood proteins will rank among the great technical challenges and require the cumulative sum of many of mankind's scientific achievements together. A variety of methods have been used to fractionate, analyze and identify proteins from blood, each yielding a small piece of the whole and throwing the great size of the task into sharp relief. The approaches attempted to date clearly indicate that enumerating the proteins and peptides of blood can be accomplished. There is no doubt that the mass spectrometry of blood will be crucial to the discovery and analysis of proteins, enzyme activities, and post-translational processes that underlay the mechanisms of disease. At present both discovery and quantification of proteins from blood are commonly reaching sensitivities of ∼1 ng/mL.

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Assessment of circulating proteasome chymotrypsin-like activity in plasma of patients with acute and chronic leukemias

Cited by 22 publications

References 26 publications

Increased plasma proteasome chymotrypsin-like activity in patients with advanced solid tumors

Increased plasma proteasome chymotrypsin-like activity in patients with advanced solid tumors

Bladder cancer detection using a peptide substrate of the 20S proteasome

Mass spectrometry of peptides and proteins from human blood

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