Mouse liver selenium-binding protein decreased in abundance by peroxisome proliferators.
Several studies with two-dimensional gel electrophoresis (2-DE) have shown that the abundance of numerous mouse liver proteins is altered in response to treatment with chemicals known to cause peroxisome proliferation. The peptide masses from tryptic digests of two liver proteins showing dramatic decreases in abundance in response to numerous peroxisome proliferators were used to search sequence databases. The selenium-binding protein 2 (SBP2 formerly 56 kDa acetaminophen-binding protein, AP 56) and selenium-binding protein 1 (SBP1 formerly 56 kDa selenium-binding protein, SP 56) in mouse liver, proteins with a high degree of sequence similarity, were the highest ranked identities obtained. Identity with SBP2 was subsequently confirmed by immunodetection with specific antiserum. Treatment of mice with 0.025% ciprofibrate resulted in the more basic of this pair of proteins being decreased to 30% of control abundance while the acidic protein was decreased to 7% of the control amount. Dexamethasone treatment, in contrast, caused increases of 80% and 20% in the abundance of the acidic and basic forms, respectively. Administration of dexamethasone to mice in combination with ciprofibrate produced expression of the acidic SBP2 at 23% of the control level and the basic SBP2 at 36%, a slightly moderated reduction compared with the decrease that occurred with ciprofibrate alone. These data suggest that peroxisome proliferators such as ciprofibrate cause a decrease in the abundance of the SBP2, which leads to increased cell proliferation, even in the presence of an inhibitor such as dexamethasone. Such a decrease in SBP, thought to serve as cell growth regulation factors, could be central to the nongenotoxic carcinogenicity of the peroxisome proliferators observed in rodents.
Giometti
C S
CS
Biosciences Division, Argonne Laboratory, IL 60439, USA. csgiometti@anl.gov
Liang
X
X
Tollaksen
S L
SL
Wall
D B
DB
Lubman
D M
DM
Subbarao
V
V
Rao
M S
MS
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002455:Cell Division; D015180:Electrophoresis, Gel, Two-Dimensional; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D020025:Peroxisome Proliferators / Q000494:pharmacology*; D051137:Selenium-Binding Proteins
D002352:Carrier Proteins; D020025:Peroxisome Proliferators; C495176:Selenbp1 protein, mouse; C495177:Selenbp2 protein, mouse; D051137:Selenium-Binding Proteins