Volatile fatty acid, metabolic by-product of periodontopathic bacteria, induces apoptosis in WEHI 231 and RAJI B lymphoma cells and splenic B cells.
The ability of butyric acid, an extracellular metabolite from periodontopathic bacteria, to induce apoptosis in murine WEHI 231 cells, splenic B cells, and human RAJI cells was examined. The culture filtrate of Porphyromonas gingivalis, Prevotella loescheii, and Fusobacterium nucleatum, which contains high a percentage of butyric acid, induced DNA fragmentation in WEHI 231 cells. Volatile fatty acid, especially butyric acid, significantly suppressed B-cell viability in a concentration-dependent fashion. The DNA fragmentation assay indicated that butyric acid rapidly induced apoptosis in WEHI 231 cells (with 1.25 mM butyric acid and 6 h after treatment), splenic B cells (with 1.25 mM butyric acid), and RAJI cells (with 2.5 mM butyric acid). Incubation of WEHI 231 cells with butyric acid for 16 h resulted in the typical ladder pattern of DNA fragmentation and the apoptoic change such as chromatin condensation and hypodiploid nuclei. Cell cycle analysis implied that butyric acid arrested the cells at the G1 phase. The inhibitory assay suggested that butyric acid-induced apoptosis of WEHI 231 and splenic B cells was inhibited by W-7, a calmodulin inhibitor. These results suggest that calmodulin-dependent regulation is involved in the signal transduction pathway of butyric acid.
Kurita-Ochiai
T
T
Department of Microbiology, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba 271, Japan. tkurita@mascat.nihon-u.ac.jp
Ochiai
K
K
Fukushima
K
K
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000187:drug effects*; D001438:Bacteroidaceae / Q000472:pathogenicity*; D002087:Butyrates / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D053938:DNA Fragmentation; D005227:Fatty Acids / Q000494:pharmacology*; D005260:Female; D005673:Fusobacterium / Q000472:pathogenicity; D045782:Hemiterpenes; D006801:Humans; D008297:Male; D051379:Mice; D010421:Pentanoic Acids / Q000494:pharmacology; D010510:Periodontal Diseases / Q000382:microbiology; D016966:Porphyromonas gingivalis / Q000472:pathogenicity; D018720:Prevotella / Q000472:pathogenicity; D011422:Propionates / Q000494:pharmacology; D015398:Signal Transduction
D002087:Butyrates; D005227:Fatty Acids; D045782:Hemiterpenes; D010421:Pentanoic Acids; D011422:Propionates; C008216:isovaleric acid; C029658:propionic acid