A novel apoptosis-inducing protein from Helicobacter pylori.
Helicobacter pylori infection induces apoptosis in gastric epithelial cells. Here, we report a novel apoptosis-inducing protein that functions as a leading factor in H. pylori-mediated apoptosis induction. We purified the protein from H. pylori by separating fractions that showed apoptosis-inducing activity. This protein induced apoptosis of AGS cells in a dose-dependent manner. The purified protein consisted of two protein fragments with molecular masses of about 40 and 22 kDa, which combined to constitute a single complex in their natural form. N-terminal sequencing indicated that both these protein fragments were encoded by the HP1118 gene. The purified protein exhibited gamma-glutamyl transpeptidase activity, the inhibition of which by 6-diazo-5-oxo-l-norleucine resulted in a complete loss of apoptosis-inducing activity. To the best of our knowledge, the apoptosis-inducing function is a newly identified physiological role for bacterial gamma-glutamyl transpeptidase. The apoptosis-inducing activity of the isogenic mutant gamma-glutamyl transpeptidase-deficient strain was significantly lower compared with that of the parent strain, demonstrating that gamma-glutamyl transpeptidase plays a significant role in H. pylori-mediated apoptosis. Our findings provide new insights into H. pylori pathogenicity and reveal a novel aspect of the bacterial gamma-glutamyl transpeptidase function.
Shibayama
Keigo
K
Department of Bacterial Pathogenesis and Infection Control, National Institute of Infectious Diseases, Tokyo 208-0011, Japan. keigo@nih.go.jp
Kamachi
Kazunari
K
Nagata
Noriyo
N
Yagi
Tetsuya
T
Nada
Toshi
T
Doi
Yohei
Y
Shibata
Naohiro
N
Yokoyama
Keiko
K
Yamane
Kunikazu
K
Kato
Haru
H
Iinuma
Yoshitsugu
Y
Arakawa
Yoshichika
Y
D017209:Apoptosis; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology; D017353:Gene Deletion; D016480:Helicobacter pylori / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D014407:Tumor Cells, Cultured; D014774:Virulence; D005723:gamma-Glutamyltransferase / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
D001426:Bacterial Proteins; D005723:gamma-Glutamyltransferase