Original ContributionImmunohistochemical analysis of paraoxonases-1, 2, and 3 expression in normal mouse tissues
Introduction
The paraoxonase (PON) multigene family comprises 3 members, PON1, PON2, and PON3 whose genes are located adjacent to each other on chromosome 7q21-22 in man and on chromosome 6 in mice [1], [2]. In humans, PON1 and PON3 gene expressions are basically only observed in the liver and kidney and their protein products are associated with high-density lipoprotein (HDL) in the circulation [3], [4], [5], [6]. On the other hand, PON2 gene expression is found in a variety of tissues, and this protein is thought to be a ubiquitously expressed intracellular enzyme but is not found in plasma [7]. The physiological role of these enzymes is still uncertain. PON1 has paraoxonase, arylesterase, and lactonase activitites [8] and plays a role in the protection against xenobiotic intoxication [9]. PON2 and PON3 are not active against organophosphate substrates, but have lactonase activity [10]. All the PONs are able to retard the oxidation of LDL, indicating an antiatherogenic role for the enzymes [11]. In addition PON2 retards cellular oxidative stress and prevents apoptosis in vascular endothelial cells [12]. Studies utilising a variety of mouse models of atherosclerosis have consistently shown that expressing human PON1, 2, or 3 inhibits or reverses the development of atherosclerosis by mechanisms involving the reduction of oxidative stress, the promotion of cholesterol efflux from macrophages, and the normalisation of vascular endothelium function [13], [14], [15], [16].
In contrast to the information provided by gene expression studies, there is a paucity of information on the histological distribution of the PON family of proteins in different tissues of humans or experimental animals. In this manuscript we describe the immunohistochemical localisation of the PON proteins in the normal mouse.
Section snippets
Animal handling and sampling
The handling of animals and the procedures described were approved by the Ethics Committee of the Rovira i Virgili University. The study was performed in two normal mice, male and female, from the C57BL/6J strain. We sacrificed the animals under anesthesia and they were perfused with saline solution for 10 min before the organs and tissues were removed. These included skin, tongue, submandibular gland, stomach, large and small intestine, liver, pancreas, brain, spinal cord, skeletal muscle,
Results
The written version of this study presents figures corresponding to 13 representative tissues or organs. The remaining figures are shown as supplementary data on line (Appendix).
Discussion
To the best of our knowledge this is the first comprehensive study of the immunohistochemical localisation of the three PON family members in a mammalian species. As such it should provide a platform to investigate changes in the distribution of these enzymes in a variety of diseases for which the mouse may be used as a convenient model. The information about the tissue distribution of PON family protein expression is scarce. At the moment, only the Swedish Human Protein Atlas program has
Acknowledgments
Supported by grants from the Instituto de Salud Carlos III (FIS 05/1607, RCMN C03/08, and RD06), Ministerio de Sanidad, Madrid, Spain. J.M. is the recipient of a postgraduate fellowship from the Generalitat de Catalunya (FI 05/00068). The authors are grateful to Esther Tous and Mònica Monterde for their invaluable technical support. Editorial assistance was provided by Dr. Peter R. Turner from t-SciMed, Reus, Spain.
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