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Butyric-acid-induced Apoptosis in Murine Thymocytes and Splenic T- and B-cells Occurs in the Absence of p53

Department of Microbiology, Nihon University School of Dentistry at Matsudo, Matsudo-shi, Chiba 271-8587, Japan

K. Ochiai

Department of Microbiology, Meikai University School of Dentistry, Sakado, Saitama 350-0283, Japan

K. Fukushima

Department of Microbiology, Nihon University School of Dentistry at Matsudo, Matsudo-shi, Chiba 271-8587, Japan

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 p21 ^WAFI/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 p21^WAF1/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 p21^WAF1/CIP1, which lower the levels of the apoptosis antagonists Bcl-2 and Bcl-XL in cells.

Key Words: butyric acid • apoptosis • p53 • knock-out mice.

Journal of Dental Research, Vol. 79, No. 12, 1948-1954 (2000)
DOI: 10.1177/00220345000790120501


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