2. Academic Validation
  3. Diabetogenic agent alloxan is a proteasome inhibitor

Diabetogenic agent alloxan is a proteasome inhibitor

  • Biochem Biophys Res Commun. 2017 Jun 24;488(2):400-406. doi: 10.1016/j.bbrc.2017.05.065.
Wenjuan Zhou 1,  Lingling Wei 1,  Ting Xiao 1,  Chunyou Lai 1,  Min Peng 1,  Lingli Xu 1,  Xiangwei Luo 1,  Shaoping Deng 1,  Fengxue Zhang 2
Affiliations

Affiliations

  • 1 Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, SC 610072, China.
  • 2 Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, SC 610072, China. Electronic address: zhangfengxue@med.uestc.edu.cn.
PMID: 28502636 DOI: 10.1016/j.bbrc.2017.05.065
Abstract

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.

Keywords

Alloxan; Diabetes; Proteasome; β-cell toxicity.

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