ARS | Publication request: BUTYRATE-INDUCED APOPTOSIS AND CELL CYCLE ARREST IN BOVINE KIDNEY EPITHELIAL CELLS: INVOLVEMENT OF CASPASE AND PROTEASOME PATHWAYS

Submitted to: BARC Poster Day
Publication Type: Abstract Only
Publication Acceptance Date: April 1, 2004
Publication Date: April 29, 2004
Citation: Li, C., Elsasser, T. 2004. Butyrate-induced apoptosis and cell cycle arrest in bovine kidney epithelial cells: involvement of caspase and proteasome pathways [abstract]. BARC Poster Day.

Technical Abstract: Beyond their nutritional impact, short chain fatty acids (SCFA), 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 G2/M in MDBK cells. The cell responses were dose-dependent. We found that at least two proteins, Cdc6 and cdk1, become targeted for destruction upon butyrate treatment. In looking into the possible mechanisms for the apoptosis and cell cycle arrest induced by butyrate, we observed that butyrate treatment activated caspase-3 activities, induced accumulation of acetylated histone, and up-regulated the expression of p21 protein. Moreover, the proteasome inhibitor MG-132 could reverse the cell cycle arrest induced by butyrate, indicating a multiprotein crosstalk wherein the ubiquitination/ proteasome pathway interacted with the caspase signaling pathway, and functionally locating the proteasome upstream of caspase3-like enzymes. All of these results suggest that butyrate functions as both a nutrient and signaling molecule regulating cell growth and proliferation.