title: Butyric-acid-induced apoptosis in murine thymocytes and splenic T- and B-cells occurs in the absence of p53.
abstract: Butyric acid, an extracellular metabolite from periodontopathic bacteria, induces apoptosis in murine thymocytes, splenic T-cells, and human Jurkat T-cells. The present study examines the contributions of apoptosis-related proteins (Bcl-2, Bcl-XL, Bax, and p21WAF1/CIP1) in the regulation of T-cell death induced by butyric acid, using p53 knock-out (p53-/-) and wild-type (p53+/+) mice. The results of a DNA fragmentation assay indicated that thymocytes, splenic T-cells, and B-cells from p53-/- mice were susceptible to butyric-acid-induced apoptosis to a degree similar to those from p53+/+ mice. Moreover, butyric acid significantly induced apoptosis in lymphocytes from both p53+/+ and p53-/- mice in a concentration- and time-dependent fashion. Experiments with fractionated subpopulations of splenic T-cells revealed that DNA fragmentation was equally observed in CD4+ and CD8+ splenic T-cells from both p53+/+ and p53-/- lymphocytes. Activation of caspase-3, caspase-6, and caspase-8, but not of caspase-1, in butyric-acid-induced T-cell apoptosis occurred regardless of the presence of p53. Western blotting analysis of splenic T-cells showed that butyric acid treatment decreased Bcl-2 and Bcl-XL expressions in p53+/+ and p53-/- cells. Splenic T-cells had barely detectable Bax and p21WAF1/CIP1, regardless of whether butyric acid and/or p53 was present. These results suggest that butyric-acid-mediated apoptosis of murine T-cells takes place via a pathway that is independent of p53, and is followed by the p53-regulated proteins Bax and p21WAF1/CIP1, which lower the levels of the apoptosis antagonists Bcl-2 and Bcl-XL in cells.
authors.affiliation: Department of Microbiology, Nihon University School of Dentistry at Matsudo, Matsudo-shi, Chiba, Japan. tkurita@mascat.nihon-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Kurita-Ochiai
authors.forename: K
authors.initials: K
authors.lastname: Ochiai
authors.forename: K
authors.initials: K
authors.lastname: Fukushima
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects; D015153:Blotting, Western; D020148:Butyric Acid / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis; D053938:DNA Fragmentation / Q000187:drug effects; D004789:Enzyme Activation; D015870:Gene Expression; D051379:Mice; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D051028:bcl-2-Associated X Protein
chemical_list: C494827:Bax protein, mouse; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D020148:Butyric Acid; D020169:Caspases