![]() |
|
|
Eppley Institute for Research in Cancer and Allied Diseases and Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198-6805
Studies on the mechanism of dietary fat and energy modulation of skin carcinogenesis suggest that these diets may act through the cellular binding site of the phorbol ester tumor promoters, protein kinase C (PKC). High-fat diets increase the activity of PKC but have no impact on the steady-state protein levels. Energy restriction reduces the activity of PKC, presumably through reduction in the steady-state levels of particular isoenzymes (PKC
and PKC
). Phorbol-binding studies with epidermal cells from mice fed energy-restricted diets indicated a reduction of phorbol-binding sites in these cells. Investigations into lipid metabolism showed that both dietary fat and energy restriction increased epidermal cell diacylglycerol (DAG). The increase in DAG in cells from energy-restricted mice may be due to increased turnover of phosphatidylinositol, as was evident in the reduced phosphatidylinositol-4-phosphate and phosphatidyl-inositol-4,5-biphosphate and elevated inositol biphosphate and inositol triphosphate in these cells.
KEY WORDS: dietary fat energy restriction protein kinase C diacylglycerol phosphatidylinositol
1 Presented as part of the symposium "Nutritional Modulation of Lipid-Mediated Signal Transduction Systems" given at Experimental Biology 94 meeting, Anaheim, CA, April 26, 1994. This symposium was sponsored by the American Institute of Nutrition and supported by a grant from the Mead Johnson Corporation. Guest editor for this symposium was Alfred H. Merrill, Jr., Emory University School of Medicine, Atlanta, GA.
2 Supported by Public Health Service Grant R01 CA42986, NCI Laboratory Support Grant CA36727 and American Cancer Society Grant SIG-16.
3 To whom correspondence should be addressed: Eppley Institute for Research in Cancer and Allied Diseases and Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, 600 South 42 Street, Omaha, NE 68198-6805.
This article has been cited by other articles:
![]() |
S. Park, S. Hong, J. Lee, S. Sung, and S. Kim Chlorpromazine attenuates pancreatic {beta}-cell function and mass through IRS2 degradation, while exercise partially reverses the attenuation J Psychopharmacol, July 1, 2008; 22(5): 522 - 531. [Abstract] [PDF] |
||||