Abstract
PON3 is a member of the paraoxonase gene family that includes PON1 and PON2. For example, PON3 and PON1 share approximately 60% identity at the amino acid level. Recent studies have demonstrated that PON3 is present in human and rabbit HDL but not in mouse HDL. Mouse PON3 appears to be cell-associated and is expressed in a wide range of tissues such as liver, adipose, macrophage, and the artery wall. In vitro studies have shown that PON3 can prevent LDL oxidation and destroy bacterial quorum-sensing molecules. Previous studies also showed that human PON3 transgenic mice were protected from obesity and atherosclerosis in both the C57BL/6 J wild-type and LDLR knockout genetic background. Administration of adenovirus expressing the human PON3 gene into apoE –/– mice also decreased atherosclerotic lesion formation. In order to further understand the functions of PON3 in physiology and disease, we performed in situ hybridization analysis to examine Pon3 gene expression patterns in newborn and adult mice, in various tissues, including atherosclerotic lesions of apoE –/– mice. Our results show relatively high levels of Pon3 mRNA labeling in the adrenal gland, submaxillary gland, lung, liver, adipose, pancreas, large intestine, and other tissues of newborn mice. In the adult mouse, Pon3 mRNA levels were much lower in the corresponding tissues as mentioned above for the newborn mouse. Sections of the aortic root from the hearts of both wild-type and apoE –/– mice displayed moderate levels of Pon3 mRNA labeling. Pon3 mRNA was also detected in the atherosclerotic lesion areas at the aortic root of apoE –/– hearts. Our data revealed that mouse Pon3 is expressed in a wide range of tissues, and that its expression is temporally controlled.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Blatter, M.C., James, R.W., Messmer, S., Barja, F., and Pometta, D. (1993). Identification of a distinct human high-density lipoprotein subspecies defined by a lipoprotein-associated protein, K-45. Identity of K-45 with paraoxonase. Eur J Biochem 211, 871–879.
Cole, T.B., Jampsa, R.L., Walter, B.J., Arndt, T.L., Richter, R.J., Shih, D.M., Tward, A., Lusis, A.J., Jack, R.M., Costa, L.G., et al. (2003). Expression of human paraoxonase (PON1) during development. Pharmacogenetics 13, 357–364.
Draganov, D.I., Stetson, P.L., Watson, C.E., Billecke, S.S., and La Du, B.N. (2000). Rabbit serum paraoxonase 3 (PON3) is a high density lipoprotein-associated lactonase and protects low density lipoprotein against oxidation. J Biol Chem 275, 33435–33442.
Draganov, D.I., Teiber, J.F., Speelman, A., Osawa, Y., Sunahara, R., and La Du, B.N. (2005). Human paraoxonases (PON1, PON2, and PON3) are lactonases with overlapping and distinct substrate specificities. J Lipid Res 46, 1239–1247.
Hassett, C., Richter, R.J., Humbert, R., Chapline, C., Crabb, J.W., Omiecinski, C.J., and Furlong, C.E. (1991). Characterization of cDNA clones encoding rabbit and human serum paraoxonase: the mature protein retains its signal sequence. Biochemistry 30, 10141–10149.
Marsillach, J., Mackness, B., Mackness, M., Riu, F., Beltran, R., Joven, J., and Camps, J. (2008). Immunohistochemical analysis of paraoxonases-1, 2, and 3 expression in normal mouse tissues. Free Radic Biol Med 45, 146–157.
Ng, C.J., Bourquard, N., Hama, S.Y., Shih, D., Grijalva, V.R., Navab, M., Fogelman, A.M., and Reddy, S.T. (2007). Adenovirus-mediated expression of human paraoxonase 3 protects against the progression of atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 27, 1368–1374.
Ng, C.J., Wadleigh, D.J., Gangopadhyay, A., Hama, S., Grijalva, V.R., Navab, M., Fogelman, A.M., and Reddy, S.T. (2001). Paraoxonase-2 is a ubiquitously expressed protein with antioxidant properties and is capable of preventing cell-mediated oxidative modification of low density lipoprotein. J Biol Chem 276, 44444–44449.
Ozer, E.A., Pezzulo, A., Shih, D.M., Chun, C., Furlong, C., Lusis, A.J., Greenberg, E.P., and Zabner, J. (2005). Human and murine paraoxonase 1 are host modulators of Pseudomonas aeruginosa quorum-sensing. FEMS Microbiol Lett 253, 29–37.
Parsek, M.R., and Greenberg, E.P. (2000). Acyl-homoserine lactone quorum sensing in gram-negative bacteria: a signaling mechanism involved in associations with higher organisms. Proc Natl Acad Sci U S A 97, 8789–8793.
Reddy, S.T., Wadleigh, D.J., Grijalva, V., Ng, C., Hama, S., Gangopadhyay, A., Shih, D.M., Lusis, A.J., Navab, M., and Fogelman, A.M. (2001). Human paraoxonase-3 is an HDL-associated enzyme with biological activity similar to paraoxonase-1 protein but is not regulated by oxidized lipids. Arterioscler Thromb Vasc Biol 21, 542–547.
Rosenblat, M., Draganov, D., Watson, C.E., Bisgaier, C.L., La Du, B.N., and Aviram, M. (2003). Mouse macrophage paraoxonase 2 activity is increased whereas cellular paraoxonase 3 activity is decreased under oxidative stress. Arterioscler Thromb Vasc Biol 23, 468–474.
Rothem, L., Hartman, C., Dahan, A., Lachter, J., Eliakim, R., and Shamir, R. (2007). Paraoxonases are associated with intestinal inflammatory diseases and intracellularly localized to the endoplasmic reticulum. Free Radic Biol Med 43, 730–739.
Shamir, R., Hartman, C., Karry, R., Pavlotzky, E., Eliakim, R., Lachter, J., Suissa, A., and Aviram, M. (2005). Paraoxonases (PONs) 1, 2, and 3 are expressed in human and mouse gastrointestinal tract and in Caco-2 cell line: selective secretion of PON1 and PON2. Free Radic Biol Med 39, 336–344.
Shih, D.M., Xia, Y.R., Wang, X.P., Wang, S.S., Bourquard, N., Fogelman, A.M., Lusis, A.J., and Reddy, S.T. (2007). Decreased obesity and atherosclerosis in human paraoxonase 3 transgenic mice. Circ Res 100, 1200–1207.
Stoltz, D.A., Ozer, E.A., Ng, C.J., Yu, J.M., Reddy, S.T., Lusis, A.J., Bourquard, N., Parsek, M.R., Zabner, J., and Shih, D.M. (2007). Paraoxonase-2 deficiency enhances Pseudomonas aeruginosa quorum sensing in murine tracheal epithelia. Am J Physiol Lung Cell Mol Physiol 292, L852–L860.
Teiber, J.F., Billecke, S.S., La Du, B.N., and Draganov, D.I. (2007). Estrogen esters as substrates for human paraoxonases. Arch Biochem Biophys 461, 24–29.
Yang, F., Wang, L.H., Wang, J., Dong, Y.H., Hu, J.Y., and Zhang, L.H. (2005). Quorum quenching enzyme activity is widely conserved in the sera of mammalian species. FEBS Lett 579, 3713–3717.
Acknowledgment
We thank Yi-Shou Shi, XuPing Wang, and Phylogeny, Inc. (Columbus, OH) for excellent technical support. This work is supported by NIH grants PO1 HL30568 (to AJL and DMS), and 2RO1 HL071776-05A1 (to DMS), and AHA grant 0755069Y (to DMS).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Humana Press, a part of Springer Science+Business Media, LLC
About this paper
Cite this paper
Shih, D.M., Xia, YR., Yu, J.M., Lusis, A.J. (2010). Temporal and Tissue-Specific Patterns of Pon3 Expression in Mouse: In situ Hybridization Analysis. In: Reddy, S. (eds) Paraoxonases in Inflammation, Infection, and Toxicology. Advances in Experimental Medicine and Biology, vol 660. Humana Press. https://doi.org/10.1007/978-1-60761-350-3_8
Download citation
DOI: https://doi.org/10.1007/978-1-60761-350-3_8
Published:
Publisher Name: Humana Press
Print ISBN: 978-1-60761-349-7
Online ISBN: 978-1-60761-350-3
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)