Evaluation of glutathione deficiency in rat livers by microarray analysis.
Hepatic glutathione content was measured and gene expression data were obtained using an Affymetrix RG U34 array after treatment with tap water containing 20mM l-buthionine (S, R)-sulfoximine (BSO) to male F344 rats for four consecutive days. Both Spearman's and Pearson's correlation coefficients were calculated between the glutathione content and the mRNA content level obtained from the microarray analysis individually. Sixty-nine gene probes, which were statistically significant (Spearman's correlation, P < 0.05) and showed a Pearson's correlation coefficients (Pearson's r) less than -0.8 between mRNA content and hepatic glutathione content, were identified as glutathione deficiency-correlated probes. By comparing the hepatic gene expression profiles between BSO- and butylated hydroxyanisole (BHA)-treated rats, 14 probes of genes that showed an increase in the corresponding gene mRNA levels only after the BSO treatment were thought to be good indicators of glutathione deficiency. A principal component analysis successfully illustrated the time-course of hepatic gene expression after the treatment with acetaminophen, phenobarbital and clofibrate, and the expression profiles were thought to reflect the changes in hepatic glutathione levels. The identified gene probes in the present study would be useful as markers for assessing hepatocellular glutathione deficiency, or oxidative stress level, based on microarray data.
Kiyosawa
Naoki
N
Medicinal Safety Research Labs., Sankyo Co. Ltd., 717 Horikoshi, Fukuroi, Shizuoka 437-0065, Japan. kiyosawa@sankyo.co.jp
Ito
Kazumi
K
Sakuma
Kyoko
K
Niino
Noriyo
N
Kanbori
Miyuki
M
Yamoto
Takashi
T
Manabe
Sunao
S
Matsunuma
Naochika
N
D000082:Acetaminophen / Q000494:pharmacology; D000818:Animals; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D020869:Gene Expression Profiling; D005978:Glutathione / Q000172:deficiency*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002083:Butylated Hydroxyanisole; D000082:Acetaminophen; D019328:Buthionine Sulfoximine; D005978:Glutathione