Altered gene expression of hepatic lanosterol 14alpha-demethylase (CYP51) in lead nitrate-treated rats.
Effects of lead nitrate (LN), a hepatic mitogen, on hepatic gene expressions of lanosterol 14alpha-demethylase (CYP51) and the sterol regulatory element binding proteins (SREBP-1a, SREBP-1c and SREBP-2), which are thought to be transcription factors for hepatic CYP51 gene, were examined by the methods of Northern blot and/or real time reverse transcriptase-polymerase chain reaction (RT-PCR). In both immature (4-week-old) and mature (7-week-old) rats, LN treatment resulted in definite increases in hepatic gene expression of CYP51 at 12 h and in the liver weight at 48 h. As for transcription factors for the CYP51 gene, enhanced gene expression of SREBP-2 was observed 6-12 h after LN treatment, whereas no enhanced gene expression of other SREBPs, SREBP-1a and SREBP-1c, was observed at any time after the treatment; for SREBP-1a, there was no significant change; for SREPB-1c, there was a drastic decrease. In addition, the serum total cholesterol level was increased 12 h after LN treatment to 7-week-old rats, and the increased level was maintained at least up to 48 h later. In the present study, we demonstrate for the first time that LN, a heavy-metal ion, activates the expression of the SREBP-2 and CYP51 genes without decreasing the serum total cholesterol level and further suggest that only SREBP-2 among SREBPs might play an important role in the LN-enhanced CYP51 gene expression.
Laboratory of Animal Gene Function, Department of Physiology and Genetic Regulation, Institute of Insect and Animal Sciences, National Institute of Agrobiological Sciences, Kannondai 2-1-2, Tsukuba, Ibaraki 305-8602, Japan. misaki@affrc.go.jp
Misaki
M
Kojima
Kiyomitsu
K
Nemoto
Uta
U
Murai
Nami
N
Yoshimura
Yuko
Y
Ayabe
Masakuni
M
Degawa
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000096:biosynthesis; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D015870:Gene Expression; D015386:Hazardous Substances / Q000633:toxicity*; D006965:Hyperplasia / Q000139:chemically induced / Q000201:enzymology; D007854:Lead / Q000633:toxicity*; D008099:Liver / Q000201:enzymology*; D008297:Male; D009566:Nitrates / Q000633:toxicity*; D010088:Oxidoreductases / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D058886:Sterol 14-Demethylase; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors / Q000096:biosynthesis
D022762:CCAAT-Enhancer-Binding Proteins; C548417:Cyp51 protein, rat; D004268:DNA-Binding Proteins; D015386:Hazardous Substances; D009566:Nitrates; D012333:RNA, Messenger; C497389:Srebf1 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors; D007854:Lead; C017461:lead nitrate; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D058886:Sterol 14-Demethylase