Measurement of peroxiredoxin-4 serum levels in rat tissue and its use as a potential marker for hepatic disease

Abstract

Abstract. Peroxiredoxin (Prx)-4, a secretable endoplasmic reticulum (ER)-resident isoform of the mammalian Prx family, functions as a thioredoxin-dependent peroxidase. It is acknowledged that Prx-4 plays a role in the detoxification of hydrogen peroxide, and potentially other peroxides, which may be generated during the oxidative folding of proteins and oxidative stress in the ER. The present study was undertaken in order to specifically quantify the tissue levels of Prx-4. To accomplish this, an enzyme-linked immunosorbent assay was developed using a specific polyclonal antibody produced by immunizing a rabbit with native recombinant rat Prx-4 protein. The assay was used to detect Prx-4 in the range of 0.1 and 10 ng/ml, and to investigate tissue distribution in rats. Using this immunoassay, we found that the serum levels of Prx-4 were substantially lower in asymptomatic Long-Evans Cinnamon rats, a rat model of Wilson's disease, compared to normal rats. In addition, the treatment of rat hepatoma cells with N-acetylcysteine led to a significant increase in the release of Prx-4 protein into the medium; thus, it appears likely that the secretion of Prx-4 is associated with the redox state within cells. These results suggest that serum Prx-4 has potential for use as a biomarker for hepatic oxidative stress.

Silencing of Peroxiredoxin-4 in Anticancer Activity of Gamma-Tocotrienol

“…A study has shown that PRDX4 is bound to the endothelium and is secreted when there is a redox change in the extracellular matrix [59]. This study is supported with the presence of high PRDX4 in the serum that indicates membrane leakage due to tissue destruction and cell apoptosis [60].…”

PRDX4 (peroxiredoxin 4)

“…Note Prx-4 has the ability to act as a hepato-protective protein due to its ability to act as an antioxidant protein, by virtue of which Prx-4 can protect the hepatic tissue against the Hydrogen peroxide as well as other reactive oxygen species causing oxidative stress. A study in rat model of Wilson's disease has demonstrated that this disease have lower level of Prx-4 expression as compared to normal (Ito et al, 2012). The same study has proposed that Prx-4 can be used as a potential biomarker of hepatic diseases as the Prx-4 serum concentration in this model was found to be quite low.…”

Physiological and pathological views of peroxiredoxin 4

“…The signal sequence is cleavable and allows the enzyme to be extracellularly released. In cultured cells, secretion of PRDX4 protein into the medium has been observed, and significant levels of PRDX4 were also detected in human and rat serum by immunological assay using specific antibodies [20,21].…”

“…Immunological assay using specific antibodies has enabled quantification of the plasma levels of PRDX4 [20,21]. However, the fate of PRDX4, either as ER resident or in secretion, appears to depend on the types of the cells, because no secretion has been observed in some types of cells [19].…”