title: Hyperhomocysteinemia-induced oxidative stress differentially alters proteasome composition and activities in heart and aorta.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Laboratory of Microbiological Engineering and Application (team of cellular physiology and molecular biology), Constantine University 1, Constantine, Algeria; Khenchela University, Khenchela, Algeria.
authors.forename: Faouzia
authors.initials: F
authors.lastname: Derouiche
authors.affiliation: INSERM Unit 1073, Rouen, France; Institute for Research and Innovation in Biomedicine, Rouen University, Rouen, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Bôle-Feysot
authors.affiliation: Laboratory of Microbiological Engineering and Application (team of cellular physiology and molecular biology), Constantine University 1, Constantine, Algeria.
authors.forename: Dalila
authors.initials: D
authors.lastname: Naïmi
authors.affiliation: 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.
authors.forename: Moïse
authors.initials: M
authors.lastname: Coëffier
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006710:Homocysteine / Q000008:administration & dosage; D020138:Hyperhomocysteinemia / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007274:Injections, Intraperitoneal; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050050:Protein Carbonylation; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D057149:Ubiquitinated Proteins / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D057149:Ubiquitinated Proteins; D006710:Homocysteine; D008315:Malondialdehyde; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D046988:Proteasome Endopeptidase Complex; D005978:Glutathione
keywords: Aorta; Heart; Homocysteine; Oxidative stress; Proteasome; ROS