PPAR pathway

Selvaraj, RK and Klasing, KC, 2006. Lutein and eicosapentaenoic acid interact to modify iNOS mRNA levels through the PPAR gamma/RXR pathway in chickens and HD11 cell lines. J Nutr 136,1610-1616. 

Chinetti G, Lestavel S, Bocher V, Re-maley AT, Neve B, Torra IP, et al. PPAR-alpha and PPAR-gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway. Nature Med 2001 7 53-58. 

Kliewer, S.A., Lehmann, J.M., Milburn, M.V. and Willson, T.M. (1999) The PPARs and PXRs nuclear xenobiotic receptors that define novel hormone signaling pathways. Recent Progress in Hormone Research, 54, 345-367. 

Not all of the biochemical events in this complex pathway from PPAR-alpha activation to tumors are completely understood, but much is known. It seems that at least some peroxisome-proliferating chemicals that also produce tumors in rodent livers do so through this pathway. If it can be demonstrated that such a mechanism is at work, then it seems that the risk of tumorigenicity for such compounds would be limited to doses that are sufficient to activate PPAK-alpha sufficiently to initiate the dangerous cascade of events within the cell. Experts have developed a number of experimental criteria that should be met if a compound is to be put in this class of carcinogens. Study of P PAR-alpha activation as a route of carcinogensis is an extremely active area of research. 

In addition to targeting adipocytes, myocytes, and hepatocytes, Tzds also have significant effects on vascular endothelium, the immune system, the ovaries, and tumor cells. Some of these responses may be independent of the PPAR-7 pathway. 

Shiner, M., Fuhrman, B., and Aviram, M., Macrophage paraoxonase 2 (PON2) expression is up-regulated by pomegranate juice phenolic antioxidants via PPAR gamma and AP-1 pathway activation, Atherosclerosis, 198, 313, 2006. 

Li AC, Glass CK. PPAR- and LXR-dependent pathways control- 92. ling lipid metabolism and the development of atherosclerosis. J. 

Figure 3 An example of the use of GC-MS for metabolic profiling. Left A section of the total ion chromatogram from the analysis of TMS-derivatized aqueous tissue extracts from the liver of PPAR- null mouse. Metabolites are identified from exact retention times and comparison of corresponding mass spectra with those in the NIST database. 97 metabolites were quantified. Right Summary of metabolite differences in the tissues of the PPAR-a null mouse. Red- increased relative to control, blue- decreased relative to control. The increased/decreased width of certain arrows reflects relative increased/decreased concentrations across these pathways, respectively.

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