title: Inhibition of cell proliferation and induction of apoptosis by Helicobacter pylori through increased phosphorylated p53, p21 and Bax expression in endothelial cells.
abstract: Microcirculation plays a crucial role in mucosal physiological function as well as repair of gastric mucosal damage. Endothelial cell damage is known to disturb microcirculation and suppress angiogenesis. Therefore, the direct effect of Helicobacter pylori on endothelial cells in vitro was investigated with H. pylori water extract. The effect of H. pylori water extract on cell proliferation and apoptosis of human umbilical vein endothelial cells (HUVECs) was evaluated. The ratio of BrdU-positive HUVECs in both cagA/vacA-positive and -negative H. pylori water extract-treated groups was significantly lower at 24 h than that in the control group, but Escherichia coli water extract did not affect the proliferation of these endothelial cells. Apoptosis was induced by H. pylori water extracts after incubation for 24 h in a cagA/vacA-independent manner. In the mitochondrial permeability transition assay, tetramethylrhodamine methyl ester was accumulated in mitochondria of HUVECs. Western blot analysis showed no difference in the level of total p53 protein in H. pylori water extract-treated and non-treated cells, but the level of phosphorylated p53 protein was increased in the treated cells at 15 and 60 min after addition of the extract. Reverse transcription (RT)-PCR products for p21 and Bax were elevated in the H. pylori water extract-treated cells. p21 levels began to increase 0.5-1 h after addition of the extract, whereas Bax increased in the period 0.5-2 h. H. pylori induced a disturbance of cell proliferation and apoptosis in the vascular endothelial cells which may contribute to gastric mucosal injury and to delayed healing of gastric lesions.
authors: Department of Gastroenterology, Juntendo University, School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors: Akihiko
authors: A
authors: Kurosawa
authors: Department of Gastroenterology, Juntendo University, School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors: Hiroto
authors: H
authors: Miwa
authors: Department of Gastroenterology, Juntendo University, School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors: Miyoko
authors: M
authors: Hirose
authors: Department of Gastroenterology, Juntendo University, School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors: Isao
authors: I
authors: Tsune
authors: Department of Gastroenterology, Juntendo University, School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors: Akihito
authors: A
authors: Nagahara
authors: Department of Gastroenterology, Juntendo University, School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors: Nobuhiro
authors: N
authors: Sato
mesh_terms: D017209:Apoptosis / Q000502:physiology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000382:microbiology* / Q000473:pathology; D015964:Gene Expression Regulation, Bacterial; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D018919:Neovascularization, Physiologic / Q000276:immunology; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014471:Umbilical Veins; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein