Spermine oxidase, a polyamine catabolic enzyme that links Helicobacter pylori CagA and gastric cancer risk

被引:50
作者
Chaturvedi, Rupesh [1 ,2 ]
de Sablet, Thibaut [1 ,2 ]
Peek, Richard M., Jr. [1 ,2 ,3 ]
Wilson, Keith T. [1 ,2 ,3 ,4 ]
机构
[1] Vanderbilt Univ, Med Ctr, Dept Med, Div Gastroenterol Elepatol & Nutr, Nashville, TN 37232 USA
[2] Tennessee Valley Healthcare Syst, Vet Affairs, Nashville, TN USA
[3] Vanderbilt Univ, Med Ctr, Dept Canc Biol, Nashville, TN USA
[4] Vanderbilt Univ, Dept Pathol Micmbiol & Immunol, Med Ctr, Nashville, TN USA
基金
美国国家卫生研究院;
关键词
polyamines; stomach; infection; epithelial cells; oxidative stress; hydrogen peroxide; DNA damage; apoptosis; Helicobacter pylori;
D O I
10.4161/gmic.19345
中图分类号
R57 [消化系及腹部疾病];
学科分类号
100201 [内科学];
摘要
We have recently reported that Helicobacter pylori strains expressing the virulence factor cytotoxin-associated gene A (CagA) stimulate increased levels of spermine oxidase (SMO) in gastric epithelial cells, while cagA(-) strains did not. SMO catabolizes the polyamine spermine and produces H2O2 that results in both apoptosis and DNA damage. Exogenous overexpression of CagA confirmed these findings, and knockdown or inhibition of SMO blocked CagA-mediated apoptosis and DNA damage. The strong association of SMO, apoptosis, and DNA damage was also demonstrated in humans infected with cagA(+), but not cagA(-) strains. In infected gerbils and mice, DNA damage was CagA-dependent and only present in epithelial cells that expressed SMO. We also discovered SMOhigh gastric epithelial cells from infected animals with dysplasia that are resistant to apoptosis despite high levels of DNA damage. Inhibition of polyamine synthesis or SMO could abrogate the development of this cell population that may represent precursors for neoplastic transformation.
引用
收藏
页码:48 / 56
页数:9
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