An antibody-based amperometric biosensor for 20S proteasome activity and inhibitor screening

The Analyst ◽  
2021 ◽  
Author(s):  
Madalina M. Barsan ◽  
Victor C. Diculescu
Keyword(s):  
Proteasome Activity ◽  
Electrochemical Methods ◽  
Amperometric Biosensor ◽  
20S Proteasome ◽  
Specific Interactions ◽  
Inhibitor Screening

The 20S proteasome is immobilized through specific interactions with antibodies and its activity is evaluated by electrochemical methods.

Temporal disruption of neuromuscular communication and muscle atrophy following non-invasive ACL injury in rats

2021 ◽  
Author(s):  
Emily R. Hunt ◽  
Steven M. Davi ◽  
Cassandra N. Parise ◽  
Kaleigh Clark ◽  
Douglas W. Van Pelt ◽  
...  
Keyword(s):  
Muscle Mass ◽  
Muscle Atrophy ◽  
Acl Injury ◽  
Quadriceps Muscle ◽  
Proteasome Activity ◽  
Vastus Lateralis Muscle ◽  
20S Proteasome ◽  
Post Injury ◽  
Non Invasive ◽  
Wet Weight

Many patients with anterior cruciate ligament (ACL) injuries have persistent quadriceps muscle atrophy, even after considerable time in rehabilitation. Understanding the factors that regulate muscle mass, and the time course of atrophic events, is important for identifying therapeutic interventions. Using a non-invasive animal model of ACL injury, a longitudinal study was performed to elucidate key parameters underlying quadriceps muscle atrophy. Male Long-Evans rats were euthanized at 6, 12, 24, 48-hrs and 1, 2, 4-wks after ACL injury that was induced via tibial compression overload; controls were not injured. Vastus Lateralis muscle size was determined by wet weight and fiber CSA. Evidence of disrupted neuromuscular communication was assessed via the expression of NCAM and genes associated with denervation and neuromuscular junction instability. Abundance of MuRF-1, MAFbx, and 45s pre-rRNA along with 20S proteasome activity were determined to investigate mechanisms related to muscle atrophy. Lastly, muscle damage-related parameters were assessed by measuring IgG permeability, centronucleation, CD68 mRNA and satellite cell abundance. Compared to controls, we observed a greater percentage of NCAM positive fibers at 6-hrs post-injury, followed by higher MAFbx abundance 48-hrs post-injury, and higher 20S proteasome activity at 1-wk post-injury. A loss of muscle wet weight, smaller fiber CSA and the elevated expression of Runx1 were also observed at the 1-wk post-injury time point relative to controls. There also were no differences observed in any damage markers. These results indicate that alterations in neuromuscular communication precede the upregulation of atrophic factors that regulate quadriceps muscle mass early after non-invasive ACL injury.

N-terminal HCV core protein fragment decreases 20S proteasome activity in the presence of PA28γ

2019 ◽  
Vol 509 (2) ◽  
pp. 590-595 ◽  
Author(s):  
Yang Zheng ◽  
Shigeru Shimamoto ◽  
Takahiro Maruno ◽  
Yuji Kobayashi ◽  
Yoshiharu Matsuura ◽  
...  
Keyword(s):  
Core Protein ◽  
Proteasome Activity ◽  
20S Proteasome ◽  
Protein Fragment ◽  
Hcv Core Protein

scholarly journals Effect of high hydrostatic pressures on 20S proteasome activity

1999 ◽  
Vol 262 (3) ◽  
pp. 900-906 ◽  
Author(s):  
Florence Gardrat ◽  
Bettina Fraigneau ◽  
Valerie Montel ◽  
Jacques Raymond ◽  
Jean-Louis Azanza
Keyword(s):  
Proteasome Activity ◽  
20S Proteasome ◽  
High Hydrostatic Pressures

Phase I trial of bortezomib in adults with recurrent malignant glioma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1567-1567 ◽  
Author(s):  
S. Phuphanich ◽  
J. Supko ◽  
K. A. Carson ◽  
S. A. Grossman ◽  
L. B. Nabors ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Malignant Glioma ◽  
Dose Level ◽  
Whole Blood ◽  
Proteasome Inhibition ◽  
Proteasome Activity ◽  
20S Proteasome ◽  
Weekly Dose ◽  
Recurrent Malignant Glioma ◽  
Grade 3

1567 Background: Bortezomib is a selective inhibitor of the proteasome that has been approved for the treatment of multiple myeloma and has also shown promising evidence of clinical activity against solid tumors. This study was undertaken to determine the maximum tolerated dose (MTD), toxicity profile, and biologic activity of bortezomib for the treatment of recurrent malignant glioma (MG). Methods: Eligible patients (pts) had supratentorial progressive MG upon radiotherapy and ≤ 1 prior regimen of chemotherapy. Dose escalation was conducted separately for pts taking enzyme inducing antiseizure drugs (EIASD+) and for those not (EIASD-). Bortezomib was given by bolus iv injection on weeks 1 and 2 of each 3 week cycle of therapy. The starting dose in both groups was 0.9 mg/m2. Cohorts of at least 3 patients were evaluated at each dose level. 20S proteasome activity was determined in whole blood lysates before and at 1 and 24 h after the first dose. Results: Fifty-nine evaluable pts (41 male/18 female) with a median age of 51 years and median KPS of 90% have been enrolled. All but 2 pts had received 1 prior chemotherapy regimen. In the EIASD- group, the weekly dose was escalated from 0.9 to 1.9 mg/m2 through 3 intermediate dose levels, with 1.7 mg/m2 established as the MTD. DLT experienced by 2 of 6 pts in the 1.90 mg/m2 dose level were grade 3 thrombocytopenia and grade 3 fatigue plus neurosensory toxicities. In the EIASD+ group, the dose has been escalated to 2.3 mg/m2 without the occurrence of any DLT. Ten additional EIASD- pts were treated at 1.7 mg/m2, with the most common adverse events being thrombocytopenia and peripheral neuropathy. The extent of proteasome inhibition in whole blood increased in a dose-dependent manner in both treatment groups. Mean proteasome inhibition in EIASD+ pts 1 h after receiving 2.1 mg/m2 of bortezomib (77 ± 12%) was similar to the 1.7 mg/m2 dose in EIASD- pts (79 ± 6%). Conclusions: The MTD for the weekly x 2 schedule of bortezomib in EIASD- patients, 1.7 mg/m2, is higher than the approved dose of 1.3 mg/m2 for the treatment of multiple myeloma. The enhanced tolerability of the drug when given together with EIASDs, for which the MTD is at least 2.1 mg/m2, is consistent with the diminished inhibition of 20S proteasome activity in these pts. No significant financial relationships to disclose.

scholarly journals PA28αβ overexpression enhances learning and memory of female mice without inducing 20S proteasome activity

2018 ◽  
Vol 19 (1) ◽  
Author(s):  
Julia Adelöf ◽  
My Andersson ◽  
Michelle Porritt ◽  
Anne Petersen ◽  
Madeleine Zetterberg ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Proteasome Activity ◽  
20S Proteasome ◽  
Female Mice

Phase I Study of the Proteasome Inhibitor Bortezomib in Pediatric Patients With Refractory Solid Tumors: A Children's Oncology Group Study (ADVL0015)

2004 ◽  
Vol 22 (23) ◽  
pp. 4804-4809 ◽  
Author(s):  
Susan M. Blaney ◽  
Mark Bernstein ◽  
Kathleen Neville ◽  
Jill Ginsberg ◽  
Brenda Kitchen ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Proteasome Inhibitor ◽  
Pediatric Patients ◽  
Maximum Tolerated Dose ◽  
Proteasome Activity ◽  
20S Proteasome ◽  
Intravenous Bolus ◽  
Recommended Phase Ii Dose ◽  
Dose Dependent ◽  
Dose Limiting Toxicity

PurposeTo determine the maximum-tolerated dose, dose-limiting toxicity (DLT), and pharmacodynamics of the proteasome inhibitor bortezomib (formerly PS-341) in children with recurrent or refractory solid tumors.Patients and MethodsAn intravenous bolus of bortezomib was administered twice weekly for 2 consecutive weeks at either 1.2 or 1.6 mg/m2/dose followed by a 1-week rest. The pharmacodynamics of bortezomib were evaluated by measurement of whole blood 20S proteasome activity.ResultsFifteen patients, 11 assessable, were enrolled between November 2001 and February 2003. Dose-limiting thrombocytopenia, which prevented administration of a complete course (four doses in 2 weeks) of therapy, occurred in two of five assessable children enrolled at the 1.6 mg/m2dose level. There were no other DLTs. Inhibition of 20S proteasome activity seemed to be dose dependent. The average inhibition 1 hour after drug administration on day 1 was 67.2% ± 7.6% at the 1.2 mg/m2/dose and 76.5% ± 3.3% at the 1.6 mg/m2/dose. There were no objective antitumor responses.ConclusionBortezomib is well tolerated in children with recurrent or refractory solid tumors. The recommended phase II dose of bortezomib for children with solid tumors is 1.2 mg/m2/dose, administered as an intravenous bolus twice weekly for 2 weeks followed by a 1-week break.

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