Unlabelled: In vitro and in vivo assessments suggest that proteasome inhibitors may be useful for modulating wound healing.

Methods: Proteasome Inhibitor I was used to assess the potential utility of proteasome inhibitors in improving wound healing in a standard rat model. Bilateral, 6 cm incisions were made 1 cm lateral to the spine of adult male Sprague Dawley rats. Animals were randomly assigned to 1 of 3 groups: no treatment (n = 15), low concentration (1% w/v, n = 15), or high concentration (5% w/v, n = 15). Treatments were applied to the left side incision at 0 hours, 24 hours, and 48 hours. Right-side incisionsreceived a vehicle, dimethyl sulfoxide, alone and independent of the assigned group, serving as both external and internal controls. Rats were sacrificed at days 7, 14, and 28 (n = 5 per group) and wounds subjected to mechanical testing and histology.

Results: No significant intergroup difference existed at 7 and 14 days. On day 28, a dosedependent increase in tensile strength with increasing Proteasome Inhibitor I was observed.

Conclusion: Results suggest dimethyl sulfoxide was not the ideal vehicle and additional improvement may be realized by optimizing the delivery method.

Download full-text PDF

Source

Publication Analysis

Top Keywords

proteasome inhibitor
12
wound healing
8
proteasome inhibitors
8
concentration w/v
8
hours hours
8
dimethyl sulfoxide
8
proteasome
5
inhibitor wound
4
healing potential
4
potential scar
4

Similar Publications

Synthesis and functional screening of novel inhibitors targeting the HDAC6 zinc finger ubiquitin-binding domain.

Eur J Med Chem

December 2024

SynBioC Research Group, Department of Green Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent, Belgium. Electronic address:

Histone deacetylase 6 (HDAC6) is a promising target for treating neurodegenerative disorders, several cancer types and viral infections. Unique among HDACs, the HDAC6 isoform possesses a zinc finger ubiquitin-binding domain (UBD) crucial for managing misfolded protein aggregates and facilitating viral infection. HDAC6 binds aggregated polyubiquitinated proteins through its UBD, mediating their transport to the aggresome and subsequent removal via autophagy.

View Article and Find Full Text PDF

Inducers of Autophagy and Cell Death: Focus on Copper Metabolism.

Ecotoxicol Environ Saf

January 2025

State Key Laboratory of Swine and Poultry Breeding Industry, Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chendu 611130, PR China. Electronic address:

Copper is an essential trace element in biological systems, playing a key role in various physiological functions, including redox reactions and energy metabolism. However, an imbalance in copper homeostasis can induce oxidative stress, mitochondrial dysfunction, and inhibition of the ubiquitin-proteasome system, ultimately leading to significant cytotoxicity and cell death. According to recent research, copper can bind to lipoylation sites on proteins involved in the tricarboxylic acid cycle, causing aggregation of lipoylated proteins, the loss of Fe-S cluster proteins, proteotoxic stress, and ultimately, cell death.

View Article and Find Full Text PDF

A novel ROR1-targeting antibody-PROTAC conjugate promotes BRD4 degradation for solid tumor treatment.

Theranostics

January 2025

Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.

Proteolysis Targeting Chimeras (PROTACs) are bifunctional compounds that have been extensively studied for their role in targeted protein degradation (TPD). The capacity to degrade validated or undruggable targets provides PROTACs with significant potency in cancer therapy. However, the clinical application of PROTACs is limited by their poor potency and unfavorable pharmacokinetic properties.

View Article and Find Full Text PDF

USP1 promotes pancreatic cancer progression and autophagy by deubiquitinating ATG14.

J Biol Chem

January 2025

Institute of Immunopharmaceutical Sciences, NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, Key Laboratory of Chemical Biology, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University, Guilin, Guangxi, China. Electronic address:

Pancreatic ductal adenocarcinoma (PDAC) is characterized by extremely poor prognosis, high mortality and limited therapeutic strategy. Autophagy is hyperactivated in PDAC and targeting autophagy are emerging as promising therapeutic strategies. The dysfunction of deubiquitinase USP1 results in tumorigenesis and chemotherapy resistance.

View Article and Find Full Text PDF

Inhibition of methionine aminopeptidase in C2C12 myoblasts disrupts cell integrity via increasing endoplasmic reticulum stress.

Biochim Biophys Acta Mol Cell Res

January 2025

Designing Future Health Initiative, Center for Promotion of Innovation Strategy, Head Office of Enterprise Partnerships, Tohoku University, Miyagi 980-8579, Japan.

Proteasome-dependent protein degradation and the digestion of peptides by aminopeptidases are essential for myogenesis. Methionine aminopeptidases (MetAPs) are uniquely involved in, both, the proteasomal degradation of proteins and in the regulation of translation (via involvement in post-translational modification). Suppressing MetAP1 and MetAP2 expression inhibits the myogenic differentiation of C2C12 myoblasts.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!