Diabetogenic agent alloxan is a proteasome inhibitor

Journal Article · Sat Jun 24 04:00:00 EDT 2017 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2017.05.065· OSTI ID:22719007

Zhou, Wenjuan; Wei, Lingling; Xiao, Ting; Lai, Chunyou; Peng, Min; Xu, Lingli; Luo, Xiangwei; Deng, Shaoping; Zhang, Fengxue

Alloxan has been used as a diabetogenic agent to induce diabetes. It selectively induces pancreatic β-cell death. The specific toxicity, however, is not fully understood. In this study, we observed the effect of alloxan on proteasome function. We found that alloxan caused the accumulation of ubiquitinated proteins in NRK cells through the inhibition of the proteolytic activities of the proteasome. Biochemistry experiments with purified 26S and 20S proteasomes revealed that alloxan directly acts on the chymotrypsin- and trypsin-like peptidase activities. These results demonstrate that alloxan is a proteasome inhibitor, which suggests that its specific toxicity toward β-cell is at least in part through proteasome inhibition. - Highlights: • Alloxan inhibits the clearance of ubiquitinated proteins. • Alloxan inhibits the clearance of recombinant proteasome substrate GFP-CL1. • Alloxan inhibits the peptidase activities of the proteasome in the NRK cell nuclear extract. • Alloxan inhibits the proteasome dependent degradation of GST-Sp1 in NRK cell nuclear extract. • Alloxan inhibits the peptidase activities of the purified 26S and 20S proteasomes.

• OSTI ID: 22719007
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 488; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ALLOXAN
APOPTOSIS
BIOCHEMISTRY
CHYMOTRYPSIN
CLEARANCE
INHIBITION
PANCREAS
TOXICITY
TRYPSIN