|Budget Amount *help
¥3,200,000 (Direct Cost : ¥3,200,000)
Fiscal Year 1999 : ¥1,400,000 (Direct Cost : ¥1,400,000)
Fiscal Year 1998 : ¥1,800,000 (Direct Cost : ¥1,800,000)
Peroxisomes appear in the cells, as cell organnelles of small size in cells and they increase the number and the size during embryonic development, by the administration of various chemicals called peroxisome proliferators, and by various external physiological stimuli. The object of the study is to elucidate the mechanism of these phenomena employing knock out mice as materials. The present study was attempted to show the mechanism regulating the morphogenesis of peroxisomes by transcription factors called PPARs, represented by PPARα. Two kinds of analyses were accomplished on PPARα knock out mouse and cultured cells inhibited the expression of PPARs by anti-sense RNA method. The results of former experiment have been present at the meetings and publications in journals, however, the latter experiments were to difficult to get results deserve publication.
RESULTS: 1) Peroxisomes appear as small spherical cell organnelles in various embryonic organs, their size, number and enzymes increase along with development. 2) The proliferation of cells and peroxisomes occur in brown adipose tissues during cold acclimation, which are regulated by the activation of PPARs. 3) The activation of PPARα induce proliferation of hepatocytes and peroxisomes, fatty liver, and hepatocellular carcinoma. 4) PPARα regulates cell cycle.
DISCUSSION: PPARα regulates the size of peroxisomes and the amount of peroxisomal enzymes, however, other factors may regulate their number. The morphogenesis of peroxisomes has been postulated that they appear as small particles, increase their size and the increase of the size result in the increase of the number. This hypothesis may not always true in every case of peroxisome proliferation. PPARα may also play important role in hepatocarcinogenesis by regulating cell cycle.