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United States Department of Agriculture

Agricultural Research Service

Title: Ubiquitin-Proteasome Pathway Is Involved in Butyrate-Induced Apoptosis and Cell Cycle Arrest in Bovine Kidney Epithelial Cells

item Li, Congjun
item Elsasser, Theodore

Submitted to: Keystone Symposia
Publication Type: Abstract Only
Publication Acceptance Date: November 17, 2004
Publication Date: July 1, 2005
Citation: Li, C.J., Elsasser, T.H. 2005. Ubiquitin-proteasome pathway is involved in butyrate-induced apoptosis and cell cycle arrest in bovine kidney epithelial cells [abstract]. Keystone Symposia, Ubiquitin and Signaling. Abstract Book. p55.

Technical Abstract: Beyond their nutritional impact, short chain fatty acids, especially butyrate, modulate cell differentiation, proliferation, motility, and in particular, they induce cell cycle arrest and apoptosis. We utilized a bovine kidney epithelial cell line (MDBK) to investigate the cell cycle regulatory and apoptotic effects of butyrate. Our results indicated that butyrate not only induced apoptosis, but also induced cell cycle arrest at the G1/S boundary and M/G2 in MDBK cells. The cell responses were dose-dependent. In looking into the possible mechanisms for the apoptosis and cell cycle arrest induced by butyrate, we observed that butyrate treatment activates caspase-3 activities and induces accumulation of acetylated histone. We also found that at least two proteins become targeted for destruction upon butyrate treatment. Cdc6 and cdk1 are significantly down-regulated by proteolytic pathways. Moreover, the proteasome inhibitor MG-132 reverses the cell cycle arrest induced by butyrate, indicating a multi-protein crosstalk wherein the ubiquitination/ proteasome pathway interacted with the caspase signaling pathway. Since proteasome inhibitor MG-132 can block activation of caspase-3, our results functionally locate the proteasome pathway upstream of caspase pathway. All of these results suggest that butyrate functions as both a nutrient and signaling molecule regulating the cell growth and proliferation.

Last Modified: 4/18/2015
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