Gene expression of drug metabolizing enzymes in adult and aged mouse liver: a modulation by immobilization stress.
The role of stress in the regulation of enzymatic systems involved in the biotransformation of xenobiotics, as well as endogenous substrates in the liver was investigated using single immobilization stress as a model. Adult (3 months of age) and aged (26 months) C3H/a male mice were used. Cytochrome P450 1A1 and 1A2 (CYP1A1 and CYP1A2), glutathione S-transferase M1 (GSTM1), aryl hydrocarbon receptor (AHR), aryl hydrocarbon receptor nuclear translocator (ARNT) and catechol-O-methyltransferase (COMT) mRNA levels in the mouse liver were measured by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) method. Excluding CYP1A1, experiments revealed significant differences in the expression of these genes between adult- and aged-control animals. The influence of stress on the expression of genes studied was shown to be higher in adult mice than in aged ones. Our results clearly demonstrate the lack of response or even the attenuation of gene expression in aged animals that may play an important role in age-related pathologies and diseases.
Mikhailova
O N
ON
Laboratory of Molecular Mechanisms of Carcinogenesis, Institute of Molecular Biology and Biophysics, Timakov Str. 2, Novosibirsk 630117, Russia. pharmacogenomics@ngs.ru
Gulyaeva
L F
LF
Filipenko
M L
ML
D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D015870:Gene Expression / Q000235:genetics*; D008658:Inactivation, Metabolic / Q000235:genetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D012333:RNA, Messenger / Q000235:genetics; D012149:Restraint, Physical; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013315:Stress, Psychological / Q000201:enzymology / Q000235:genetics*
D012333:RNA, Messenger