Mouse plasma glutathione peroxidase. cDNA sequence analysis and renal proximal tubular expression and secretion

Abstract

A mouse kidney cDNA isolated by differential screening was found to be highly homologous to rat, human, and bovine plasma glutathione peroxidase (GPx) sequences. Analysis of the full-length coding region sequence demonstrated an in-frame selenocysteine-encoding opal codon and putative signal sequence, suggesting that the sequence represents the mouse homolog of plasma GPx. The level of expression of plasma GPx in various mouse tissues and during development was investigated by Northern blot analysis. Plasma GPx mRNA was observed to be very abundant in kidney compared with placenta, epididymis, intestine, lung, heart, testis, ovary, salivary gland, spleen, thymus, stomach, brain, and fetal kidney and could not be detected in pancreas or in liver except from pregnant mice. In addition, plasma GPx mRNA levels were shown to increase during postnatal development of the kidney. In situ hybridization localized plasma GPx mRNA to proximal tubules, while primary cell culture demonstrated that plasma GPx is synthesized and secreted by proximal tubular epithelial cells. The relative abundance of plasma GPx mRNA in mouse kidney suggests that proximal tubules may be the primary source of the enzyme detectable in plasma and further suggests that plasma GPx has an important function in protecting the kidney from oxidative damage.