Protein variability in male and female Wistar rat liver proteins

Abstract

In the emerging field of mechanistic toxicology, growing attention is being paid to the interpretation of sex-related toxic responses. The Wistar rat outbred stock is a frequently used rodent for toxicity testing. Outbred strains, which display a relatively high degree of genetic variability between the individual animals are often used in risk assessment, as they are considered to best approximate the variability present in a human population. In this study two-dimensional (2-D) protein gel electrophoresis was applied to investigate the liver protein patterns of male and female Wistar rats and to search for (i) sex-related and (ii) interindividual qualitative and quantitative differences in protein expression. Among the sexes, six proteins were detected that were shown to be exclusively present in male rats and one that was present only in females. A male-specific protein was tentatively assigned to alpha 2u globulin. Seven protein spots showed statistically significant abundance changes (p < 0.001) between males and females, one was tentatively assigned to heme oxygenase 1 and another to the 23 kDa morphin-binding protein. Four sets of protein spots were detected that showed positional shifts in the individual patterns and are likely to represent polymorphic proteins inherent in the Wistar rat. These results form a valuable basis for future investigations of drug-induced changes in the male and female Wistar rat liver pattern.

Differences in protein level between neonatal and adult brain

“…In the liver, several sex-specific proteins have been identified [4]. A surprising finding in the brain was an inconsistency in the molecular mass of GFAP in male rats.…”

“…The analysis of animal-tissue-derived proteins by 2-D electrophoresis can be complicated because of eventual differences in the level, resulting from allelic differences and from other differences derived from certain physiological conditions, such as age and sex. Sex-and agerelated differences in the protein level in rats have been reported for serum [1,2], liver [3,4], and urine [5]. In this study, we investigated the differential protein expression in the brain, associated with age and sex of the animals.…”

Nuclear matrix protein expressions in hepatocytes of normal and cirrhotic rat livers under normal and regenerating conditions

“…Recently, a database of the rat liver cells as an in vivo biological system was developed to explore gene expression effects involving regulation of cholesterol synthesis by cholesterol-lowering drugs and a high-cholesterol diet using 2-D gel electrophoresis [Anderson et al, 1991[Anderson et al, , 1995. The liver protein patterns of male and female Wistar rats were investigated and sex-related proteins were detected [Steiner et al, 1995].…”

Determination of variations in gene expression during fracture healing

“…Similarly, Anderson et al (1985) found an approximate overall 15% coefficient of variation when measuring the coomassie blue staining intensities of specific mouse liver proteins from the same extract separated by 2-D gel electrophoresis as measured in 10 independent gels. In a similar analysis using 2-D gels to separate rat liver proteins, Steiner et al (1995) found an approximate 20% variation in protein amounts from 10 2-D gels of the same protein extract. Considering that the independent cDNA preparations we used underwent additional manipulations (PCR) before quantification by polyacrylamide gel electrophoresis, the approximate 24% coefficient of variation we found between two different housekeeping gene mRNA amounts is not an unexpected finding.…”