Effect of serum cholesterol on the mRNA content of amyloid precursor protein in rat livers.
Genes that showed mRNA content profiles, which correlated with serum concentrations of total cholesterol (T.CHO), were screened from the microarray data of phenobarbital (PB)- or clofibrate (CLO)-treated rat livers, and the correlation was evaluated based on Spearman's correlation coefficient. Many genes involved in the cholesterol or bile acid metabolism were highly correlated such as UDP-glucuronosyltransferase-21, apolipoprotein A-I and cMOAT. The mRNA content of the amyloid precursor protein (APP) showed the 5th highest correlation among the 8799 probes in the Affymetrix Rat Genome U34 Array. In the livers of rats fed a high-cholesterol (1%) diet for 33 days, serum T.CHO levels increased by 4.6-fold, and the hepatic APP mRNA content also increased by 1.9-fold compared to the control group. These data suggest that the hepatic APP mRNA content was affected by serum T.CHO, and that hepatic APP was involved in cholesterol metabolism in rat livers.
Kiyosawa
Naoki
N
Medicinal Safety Research Labs., Sankyo Co. Ltd., 717 Horikoshi, Fukuroi, Shizuoka 437-0065, Japan. kiyosawa@fuku.sankyo.co.jp
Ito
Kazumi
K
Niino
Noriyo
N
Sakuma
Kyoko
K
Kanbori
Miyuki
M
Yamoto
Takashi
T
Manabe
Sunao
S
Matsunuma
Naochika
N
D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D002784:Cholesterol / Q000097:blood* / Q000494:pharmacology; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D002994:Clofibrate / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010634:Phenobarbital / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016564:Amyloid beta-Protein Precursor; D002791:Cholesterol, Dietary; D012333:RNA, Messenger; D002784:Cholesterol; D002994:Clofibrate; D010634:Phenobarbital