Upregulation of myocardial 11S-activated proteasome in experimental hyperglycemia

Saul R. Powell, Samson Mathews Samuel, Ping Wang, Andras Divald, Mahesh Thirunavukkarasu, Srikanth Koneru, Xuejun Wang, Nilanjana Maulik

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

This study examined the hypothesis that the ubiquitin proteasome system (UPS) degrades proteins damaged by exposure to hyperglycemia. Experimental hyperglycemia was induced in male rats by treatment with streptozotocin. After 30 days, echocardiography confirmed the presence of cardiomyopathy as ejection fraction, fractional shortening, and diastolic function (E/A ratio) were decreased, and chamber diameter was increased in hyperglycemic animals. Proteasome non-ATP-dependent chymotryptic activity was increased over 2-fold in hyperglycemic hearts, but the ATP-dependent activity was decreased and levels of ubiquitinated proteins were increased. Protein levels of the PA28α of the 11S-activator ring were increased by 128% and the PA28β subunit increased by 58% in the hyperglycemic hearts. The α3 subunit of the 20S-proteasome was increased by 82% while the catalytic β5 subunit was increased by 68% in hyperglycemic hearts. Protein oxidation as indicated by protein carbonyls was significantly higher in hyperglycemic hearts. These studies support the conclusion that the UPS becomes dysfunctional during long term hyperglycemia. However, 11S-activated proteasome was increased suggesting a response to oxidative protein damage and a potential role for this form of the proteasome in a cardiac pathophysiology.

Original languageEnglish (US)
Pages (from-to)618-621
Number of pages4
JournalJournal of Molecular and Cellular Cardiology
Volume44
Issue number3
DOIs
StatePublished - Mar 2008

Keywords

  • Cardiomyopathy
  • Hyperglycemia
  • PA28
  • Protein oxidation
  • Ubiquitin proteasome system

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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