An old adage once held that stomach ulcers arise from “hurry, worry, and curry.” Scientists dispelled that notion in the early 1980s with the discovery that the bacterium Helicobacter pylori causes most such ulcers. Twenty years later, with the modern knowledge that half the world’s people harbor H. pylori in their stomachs, scientists remain baffled as to why only a fraction of these infections leads to ulcers.
Research in mice now suggests that a protein on the surface of cells paves the way for a toxin produced by H. pylori to damage the stomach lining.
Earlier tests had turned up the protein, known as Ptprz, on cells exposed to
H. pylori toxin in lab dishes, says Masaharu Noda, a molecular neurobiologist at the National Institute for Basic Biology in Okazaki, Japan. Other research had indicated that the toxin destabilizes cells by causing the development of acid-filled compartments in them (SN: 10/4/97, p. 218).
To determine whether Ptprz plays a role in ulcers, Noda and his colleagues gave 24 mice oral doses of the H. pylori toxin called VacA. Half the mice lacked the gene that encodes Ptprz; the others produced the protein. Mice without Ptprz showed no ill effects from VacA. Within days of receiving the toxin, 10 of the 12 other mice formed ulcers, the researchers report in the March Nature Genetics.
Oddly, acid-filled compartments formed in the stomach cells of both groups, suggesting that this isn’t the way H. pylori causes ulcers. Instead, the researchers note that the VacA-Ptprz combination disrupts bonds between stomach cells.
Ptprz belongs to a family of proteins involved in cell-to-cell adhesion, says Richard M. Peek Jr. of Vanderbilt University School of Medicine in Nashville. The findings show that when VacA binds to Ptprz on cells, it initiates signals that induce those cells to detach from one another, he says. This tissue breakdown in the stomach lining could expose deeper layers of cells to harsh digestive acids–a recipe for ulcers, Peek says.
Once scientists understand the interplay between VacA and Ptprz, they might recognize a target for a vaccine against ulcers, he says. Or, measurements of Ptprz could identify people at high risk of developing ulcers, Peek says.
The new animal data imply that “if some people produce excess Ptprz, they would have greater risk,” Noda reasons. However, scientists don’t know much about Ptprz’ function and prevalence in people. Shutting off Ptprz doesn’t seem to cause side effects, Noda says.
If you have a comment on this article that you would like considered for publication in Science News, please send it to email@example.com.