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 pe ptide masses from tryptic digests of two liver proteins showing dramatic de creases in abundance in response to numerous peroxisome proliferators were used to search sequence databases. The selenium-binding protein 2 (SBP2 for merly 56 kDa acetaminophen-binding protein, AP 56) and selenium-binding pro tein 1 (SBP1 formerly 56 kDa selenium-binding protein, SP 56) in mouse live r, proteins with a high degree of sequence similarity, were the highest ran ked identities obtained. Identity with SBP2 was subsequently confirmed by i mmunodetection with specific antiserum. Treatment of mice with 0.025% cipro fibrate 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% o f the control amount. Dexamethasone treatment, in contrast, caused increase s of 80% and 20% in the abundance of the acidic and basic forms, respective ly. Administration of dexamethasone to mice in combination with ciprofibrat e produced expression of the acidic SBP2 at 23% of the control level and th e basic SBP2 at 36%, a slightly moderated reduction compared with the decre ase that occurred with ciprofibrate alone. These data suggest that peroxiso me 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 SEP, thought to serve as cell growth regulation factors, could be central to the nongenotox ic carcinogenicity of the peroxisome proliferators observed in rodents.