Abstract
Dietary restriction is known to decrease cell proliferation and increase apoptosis in the liver; however, the role of withdrawal of single dietary factors on cells of the liver is less well understood. In this study, we investigated the effects of short-term choline deficiency (CD; also for choline deficient) on cell survival, proliferation and the expression of proteins related to the transforming growth factor-beta1 (TGF-beta1) growth-inhibitory signaling pathway in the liver. In animals fed a CD diet for 6 weeks, classical apoptotic bodies were detected in 0.28 +/- 0.04% of hepatocytes in CD livers compared to 0.096 +/- 0.006% of hepatocytes in control rats fed a choline-sufficient (CS) diet. These classical apoptotic cells exhibited DNA fragmentation when probed with an in situ end-labeling immunohistochemical method; TUNEL-positive nuclei were also seen in hepatocytes in CD livers which had accumulated large amounts of lipid, consistent with the known DNA-damaging effects of CD. In CS control livers, TGF-beta1 protein was found only in bile duct epithelium and nonparenchymal-type cells, and not in hepatocytes. However, the majority of hepatocytes in the CD liver expressed high levels of TGF-beta1 protein, as well as TGF-beta1 receptor types I and II. Nuclear localization of p27Kip1 protein, which may link TGF-beta1 expression to apoptosis, showed a 10-fold increase in CD hepatocytes (4.1 +/- 1.1 vs. 0.35 +/- 0.04% of cells) compared to controls. In addition, there was a 5-fold increase (0.54 +/- 0.031 vs. 0.011 +/- 0.007% of cells) in the mitotic index in CD-compared control livers. We conclude that feeding a CD diet for 6 weeks induces apoptosis in hepatocytes in the whole rat liver and that this form of cell death appears to be mediated, in part, by TGF-beta1 and related proteins.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.