PMID- 25194809 OWN - NLM STAT- MEDLINE DCOM- 20150225 LR - 20140929 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 452 IP - 3 DP - 2014 Sep 26 TI - Hyperhomocysteinemia-induced oxidative stress differentially alters proteasome composition and activities in heart and aorta. PG - 740-5 LID - S0006-291X(14)01582-4 [pii] LID - 10.1016/j.bbrc.2014.08.141 [doi] AB - 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 (0.6-1.2muM/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. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Derouiche, Faouzia AU - Derouiche F AD - Laboratory of Microbiological Engineering and Application (team of cellular physiology and molecular biology), Constantine University 1, Constantine, Algeria; Khenchela University, Khenchela, Algeria. FAU - Bole-Feysot, Christine AU - Bole-Feysot C AD - INSERM Unit 1073, Rouen, France; Institute for Research and Innovation in Biomedicine, Rouen University, Rouen, France. FAU - Naimi, Dalila AU - Naimi D AD - Laboratory of Microbiological Engineering and Application (team of cellular physiology and molecular biology), Constantine University 1, Constantine, Algeria. FAU - Coeffier, Moise AU - Coeffier M AD - INSERM Unit 1073, Rouen, France; Institute for Research and Innovation in Biomedicine, Rouen University, Rouen, France; Rouen University Hospital, Nutrition Unit, Rouen, France. Electronic address: moise.coeffier@chu-rouen.fr. LA - eng PT - Journal Article DEP - 20140904 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Ubiquitinated Proteins) RN - 0LVT1QZ0BA (Homocysteine) RN - 4Y8F71G49Q (Malondialdehyde) RN - EC 1.11.1.6 (Catalase) RN - EC 1.11.1.9 (Glutathione Peroxidase) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 3.4.25.1 (Proteasome Endopeptidase Complex) RN - GAN16C9B8O (Glutathione) SB - IM MH - Animals MH - Aorta/*metabolism/pathology MH - Catalase/genetics/metabolism MH - Gene Expression Regulation MH - Glutathione/metabolism MH - Glutathione Peroxidase/genetics/metabolism MH - Homocysteine/administration & dosage MH - Hyperhomocysteinemia/chemically induced/genetics/*metabolism/pathology MH - Injections, Intraperitoneal MH - Male MH - Malondialdehyde/metabolism MH - Myocardium/*metabolism/pathology MH - Oxidation-Reduction MH - Oxidative Stress MH - Proteasome Endopeptidase Complex/chemistry/genetics/*metabolism MH - Protein Carbonylation MH - Rats MH - Rats, Wistar MH - Signal Transduction MH - Superoxide Dismutase/genetics/metabolism MH - Ubiquitinated Proteins/genetics/metabolism MH - Ubiquitination OTO - NOTNLM OT - Aorta OT - Heart OT - Homocysteine OT - Oxidative stress OT - Proteasome OT - ROS EDAT- 2014/09/10 06:00 MHDA- 2015/02/26 06:00 CRDT- 2014/09/08 06:00 PHST- 2014/08/19 00:00 [received] PHST- 2014/08/26 00:00 [accepted] PHST- 2014/09/08 06:00 [entrez] PHST- 2014/09/10 06:00 [pubmed] PHST- 2015/02/26 06:00 [medline] AID - S0006-291X(14)01582-4 [pii] AID - 10.1016/j.bbrc.2014.08.141 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2014 Sep 26;452(3):740-5. doi: 10.1016/j.bbrc.2014.08.141. Epub 2014 Sep 4.