Hyperhomocysteinemia-induced oxidative stress differentially alters proteasome composition and activities in heart and aorta.

Abstract

BACKGROUND AND AIMS:

Hyperhomocysteinemia (HHcy) is associated with cardiovascular diseases and is thought to induce endogenous oxidative stress and causes many cellular damages. Proteasome that degrades oxidized and ubiquitinated proteins can regulate the cellular response to oxidative stress. We aimed to investigate whether hyperhomocysteinemia induces oxidative stress and alters proteasome function and composition in heart and aorta tissues of rat.

METHODS AND RESULTS:

To create hyperhomocysteinemia, male Wistar rats (Pasteur Institute-Algiers) were received daily intraperitoneal injections of dl-homocysteine (0.6-1.2μM/g body weight) for 3weeks. Biomarkers of oxidative stress (malondialdehyde (MDA), protein carbonyl (PC), superoxide dismutase (SOD) and catalase (CAT)) were first measured by biochemical methods and tissue damages by histological sections. Proteasome activities were quantitated using fluorogenic synthetic peptides; ubiquitinated proteins and proteasome subunits expression were then evaluated by SDS PAGE and Western blot analysis. We showed increased MDA and PC but decreased SOD and CAT levels both in plasma, heart and aorta accompanied by histological changes. A significant decrease of proteasome activities was observed in heart, whereas proteasome activity was not affected in aorta. However proteasome composition was altered in both tissues, as the accumulation of ubiquitinated proteins.

CONCLUSION:

Data demonstrated an alteration of the ubiquitin-proteasome system in hyperhomocysteinemia as a result of accumulating oxidized and ubiquitinated proteins in response to oxidative stress. Further studies must be conducted to better understanding mechanisms responsible of proteasome alterations in hyperhomocysteinemia.

• Authors: Faouzia Derouiche, Christine Bôle-Feysot, Dalila Naïmi, Moïse Coëffier
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 452 Issue 3 Pg. 740-5 (Sep 26 2014) ISSN: 1090-2104 [Electronic] United States
• PMID: 25194809 (Publication Type: Journal Article)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Ubiquitinated Proteins
• Homocysteine
• Malondialdehyde
• Catalase
• Glutathione Peroxidase
• Superoxide Dismutase
• Proteasome Endopeptidase Complex
• Glutathione

Topics

• Animals
• Aorta (metabolism, pathology)
• Catalase (genetics, metabolism)
• Gene Expression Regulation
• Glutathione (metabolism)
• Glutathione Peroxidase (genetics, metabolism)
• Homocysteine (administration & dosage)
• Hyperhomocysteinemia (chemically induced, genetics, metabolism, pathology)
• Injections, Intraperitoneal
• Male
• Malondialdehyde (metabolism)
• Myocardium (metabolism, pathology)
• Oxidation-Reduction
• Oxidative Stress
• Proteasome Endopeptidase Complex (chemistry, genetics, metabolism)
• Protein Carbonylation
• Rats
• Rats, Wistar
• Signal Transduction
• Superoxide Dismutase (genetics, metabolism)
• Ubiquitinated Proteins (genetics, metabolism)
• Ubiquitination