Selenium‐binding protein 2, the major hepatic target for acetaminophen, shows sex differences in protein abundance

Abstract

Liver samples from female and male mice of two subspecies, Mus musculus musculus and Mus musculus domesticus, were investigated by a combination of 2-DE and MALDI-MS. The image analysis of the generated 2-DE patterns revealed several protein spots with significant differences in intensity/abundance between the sexes. Seven protein spots, which were prominent in 2-DE patterns of male mice, but which showed very low intensities in females, were identified as selenium-binding protein 2 (SBP2) also known as 56-kDa acetaminophen-binding protein. Edman degradation indicated that at least three of these protein spots represent N-terminally truncated SBP2 variants. Furthermore, it was shown that the observed differences in SBP2 abundance correlate with sex differences in transcription of the gene encoding SBP2, selenbp2, as revealed by RT-PCR and restriction digest as well as sequence analysis of the products. Since SBP2 has been described as the major target for acetaminophen in mouse liver cytosol, these findings are discussed with respect to their possible relevance for sex differences in acetaminophen-mediated toxicity, which have been described in a variety of mammals including mice and rats.

Stress resistance and aging: Influence of genes and nutrition

“…Sex-specific differences are well described in both rat and mouse models of APAP toxicity, and are the result of variation in biotransformation pathways (Galinsky et al, 1990;Hoivik et al, 1995;Tarloff et al, 1996;Mugford and Tarloff, 1997) and the abundance of specific target proteins in cellular membranes (Mattow et al, 2006). Although males are typically more susceptible to APAP-toxicity, in this study we found that GHR-KO females exhibited a higher degree of mortality after APAP injection relative to males.…”

Proteomic Analysis of the Rat Ovary Following Chronic Low-Dose Exposure to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD)

“…Selenium-binding protein 2 (SBP2), also known as 56-kD acetaminophen-binding protein (Mattow et al, 2006), has specific binding properties for selenium and APAP (N-acetylp-aminophenol) (Lanfear et al, 1993). Our findings show that SBP2 expression in the ovary was significantly higher in TCDD-treated female rats.…”

Proteomic Analysis of Membrane-Associated Proteins from Rat Liver Autophagosomes

“…8 (54 kDa; pI 6.3) was unequivocally identified as selenium-binding protein 2 (SBP2) by 21/42 peptides (p = 6.1e-18) and a sequence coverage of 48% (Table 12). No peptide was recovered from the N-terminus, which has been reported to be blocked in the mouse liver, 169 but inclusion of the 8-23 peptide as well as the C-terminal peptide, along with the high mass value (54 kDa, i.e., comparable to the mass of 53 kDa calculated for this protein), would indicate that the autophagosomal SBP2 represents the full-length protein. In the mouse, SBP2 is most highly expressed in the liver; 170 where as many as five isoelectric point variants may be found.…”