Helicobacter pylori induces mono-(adenosine 5'-diphosphate)-ribosylation in human gastric adenocarcinoma.
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| Abstract |
Mono-(adenosine 5'-diphosphate) (ADP)-ribosylation, which transfers an ADP-ribose from nicotinamide adenine dinucleotide (NAD) to an acceptor protein, is an important post-translational modification of cellular proteins. Several bacterial toxins are known to possess the mono-ADP-ribosyltransferase activity to catalyze this reaction as a possible pathogenic factor. Therefore, the aim of this study was to examine whether H. pylori may also induce mono-ADP-ribosylation in a human gastric mucosal protein in association with gastric cancer development. Tumorous and adjacent non-tumorous mucosal tissue specimens were obtained from the surgically removed stomachs of 5 patients with gastric adenocarcinoma, and then were homogenized into cytosolic and membranous fractions. Each homogenate or an H. pylori extract was assayed for mono-ADP-ribosylation with [adenylate-(32)P]-NAD and 3-aminobenzamide, a potent inhibitor of poly-ADP-ribosylation. The radiolabeled proteins were separated by sodium dodecylsulfate-polyacrylamide gel electrophoresis followed by radio-image analysis. In the extracts from H. pylori, a strain-dependent, endogenous radiolabeling of 70-kDa protein was detected. An assay of the membranous fractions from 5 gastric adenocarcinomas with the extract of OMH4, a clinical H. pylori isolate, revealed notable radiolabelings of 55- and 45-kDa proteins, which were not found without the OMH4 extract. In contrast, the radiolabelings were minimal in the membranous fractions from respective non-tumorous mucosae, and they were not detected in any of the examined cytosolic fractions. All three radiolabelings of 70-, 55-, and 45-kDa proteins were dependent on NAD, but not on ADP-ribose. Snake venom phosphodiesterase digestion of the 3 radiolabeled proteins released only AMP. We thus found that H. pylori had an enzymatic mono-ADP-ribosyltransferase activity which enabled it to modify the 55- and 45-kDa membranous proteins of human gastric adenocarcinoma, as well as the 70-kDa protein of H. pylori itself. The possible roles underlying our observations on carcinogenesis or development of human gastric carcinoma are yet to be elucidated.
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| Authors | Takashi Akai, Yoshihiro Nabeya, Kinnosuke Yahiro, Naoko Morinaga, Kanae Mitsuhashi, Masahito Inoue, Akio Sakamoto, Takenori Ochiai, Masatoshi Noda |
| Journal | International journal of oncology (Int J Oncol) Vol. 29 Issue 4 Pg. 965-72 (Oct 2006) ISSN: 1019-6439 [Print] Greece |
| PMID | 16964392 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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