title: Proteasome activity deregulation in LEC rat hepatitis: following the insights of transcriptomic analysis.
abstract: LEC rats show spontaneous hepatitis and hepatocarcinoma development related to oxidative stress due to abnormal copper accumulation in the liver. We used DNA microarrays bearing 22,012 genes to investigate at the transcriptomic level the progression of the hepatitis in LEC rats in comparison to a control obtained from LEC rats treated with D-penicillamine, a copper chelating agent known to block hepatitis development. Multivariate statistical analyses as partial least square (PLS) regression between transcriptomic data and hepatitis markers in plasma led us to select 483 genes related to hepatitis development in these rats. After a complementary discriminant analysis (PLS-DA), 239 important genes for the separation between the different rat groups were selected. Gene ontology classification revealed an overrepresentation of genes involved in protein metabolism-related functions. More importantly, some genes implicated in proteasome pathway were upregulated. However, analysis of 20S proteasome activity showed that trypsin-like and peptidylglutamyl peptide hydrolase activities were diminished during hepatitis. Because oxidative stress is known to promote the inactivation of the proteasome complex, we propose the deregulation of the proteasome genes expression as a result of oxidative inactivation of proteasome activity during hepatitis in LEC rats. These results bring new insights in the hepatitis and the hepatocarcinogenesis development.
authors: INRA, UMR 1089-Xénobiotiques, F-31000, Toulouse, France.
authors: Adriana
authors: A
authors: Marquez-Quiñones
authors: Alain
authors: A
authors: Paris
authors: Balbine
authors: B
authors: Roussel
authors: Julio
authors: J
authors: Perez-Carreon
authors: Véronique
authors: V
authors: Le Berre
authors: Jean Marie
authors: JM
authors: François
authors: Saúl
authors: S
authors: Villa-Treviño
authors: Françoise
authors: F
authors: Guéraud
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006520:Hepatitis, Animal / Q000201:enzymology* / Q000235:genetics; D016018:Least-Squares Analysis; D008297:Male; D015999:Multivariate Analysis; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D051381:Rats; D020332:Rats, Inbred LEC
chemical_list: D046988:Proteasome Endopeptidase Complex