Future work will be required to estab lish the role of immune physiology and cellular defence mechanisms in the regenerating fish skin and also the involvement of stem cells in this process. Inhibitors,Modulators,Libraries At the same time as the immune response, there is a clear requirement to rapidly re construct this external bar rier with various genes involved in metabolic processes Inhibitors,Modulators,Libraries such Brefeldin_A as amino acid biosynthesis and also cell division and proliferation. Interestingly, in a link with the IPA results, several of these genes have been described in cancer stu dies.
Cyclin dependant kinase inhibitor Inhibitors,Modulators,Libraries is involved in hae matopoietic cell cycle regulation and has been shown to be over expressed in breast and prostate cancer, S phase kinase associated protein interacts with c myc dur ing the G1 S phase transition of the cell and is a co factor of c myc which is a known transcriptional regulator of oncoproteins and involved in cell growth, apoptosis and oncogenesis, whilst the mitotic check point serine threonine protein kinase has been shown to be preferen tially expressed in cells with a high mitotic index. Adaptation to new conditions involves an element of cytoskeletal re modelling, as evidenced by the up reg ulation of cytokeratin which has been associated with epi dermis development, fibrinolysis and also regulation of angiogenesis. It is tempting to speculate that the up regu lation of cytokeratin in response to scale removal may represent a keratinization like phenotype provoked by the osmotic shock.
There was also up regulation of genes involved in apoptosis such as Galectin 3 and the multi functional S phase kinase associated protein and the somewhat confusingly named cation trans port regulator like protein. Hence competing inter ests Inhibitors,Modulators,Libraries between infection inflammation control and cellular proliferation tissue repair in fish with scales removed appear to be ongoing. The effect of food deprivation with no scale removal Skin tissue metabolism is clearly being redirected as the animals cope with adaptation to food deprivation. One he up regulation of angiopoietin related protein 4, MYND and KIAA0711, all of which have been shown to play roles in the inhibition of proliferation. Another regulator of a proto oncogene is present in the form of ubiquitin carboxyl terminal hydrolase and levels of MYC decline is response to intracellular stress signals. Molecular signals of cell stress are also present with up regulation of antioxidants. During periods of food deprivation fish seem to main tain energy homeostasis, at least during the initial stages of fasting, by mobilizing energy reserves such as lipids and hepatic glycogen and reduction in the rate of glu cose utilization and enhancement of lipid metabolism.