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Gender‐related difference in altered gene expression of a sterol regulatory element binding protein, SREBP‐2, by lead nitrate in rats: Correlation with development of hypercholesterolemia
Author(s) -
Kojima Misaki,
Degawa Masakuni
Publication year - 2006
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.1138
Subject(s) - sterol regulatory element binding protein , sterol , medicine , endocrinology , gene expression , cholesterol , reductase , biology , hmg coa reductase , gene , enzyme , chemistry , biochemistry
Changes in gene expression levels of hepatic sterol regulatory element binding protein‐2 (SREBP‐2) and 3‐hydroxy‐3‐methylglutaryl‐CoA reductase (HMGR) after a single i.v. injection of lead nitrate (LN, 100 µmol kg −1 body weight) were examined comparatively by real time reverse transcriptase‐polymerase chain reaction (RT‐PCR) in male and female rats. Significant increases in the gene expression level of SREBP‐2, a transcription factor for the HMGR gene, occurred at 6–12 h in male and at 24–36 h in female rats after LN‐treatment. The gene expression level of HMGR, a rate‐limiting enzyme for cholesterol biosynthesis, significantly increased at 3–48 h in male rats and 12–48 h in female rats. Subsequently, significant increases in the amount of hepatic total cholesterol in male and female rats were also observed at 3–48 h and 24–48 h, respectively. The present findings demonstrate that increases in gene expressions of hepatic SREBP‐2 and HMGR and the amount of hepatic total cholesterol by LN occur earlier in male rats than in the females, and that increases in the gene expression level of HMGR and the amount of hepatic total cholesterol occur prior to the increase in the gene expression level of SREBP‐2 in either sex of rats. Copyright © 2006 John Wiley & Sons, Ltd.