HELICOBACTER PYLORI INFECTION IN THE MOUSE REDUCES METALLOTHIONEIN EXPRESSION.

Cuong D Tran, Ross N Butler, Hien Huynh, Fiona Campbell & Peter Coyle:
Digestive Disease Week, 20-23 May, 2001, Atlanta, Georgia.

ABSTRACT:

Metallothionein (MT) is a ubiquitous low molecular weight cysteine-rich heavy metal-binding protein involved in metal detoxification and regulation of zinc metabolism. MT can also protect against oxidative damage by sequestering reactive oxygen species (ROS). Helicobacter pylori (Hp) is a gram-negative bacterium affecting about half the world's population, causing gastric inflammation possibly via enhanced production of reactive oxygen species in gastric epithelium. Thus, MT has potential in gastric protection against Hp infection. However, little is known about the role of MT in inhibiting Hp-induced gastritis. The aim of this study was to investigate the relationship between MT and Hp infection in a mouse model. C57Bl/6 mice were infected with 1 X 107 Hp/ml (SS1 strain). Bacterial load was determined by culturing homogenized gastric tissue on Helicobacter-selective agar plates. MT concentration in gastric tissue was determined using the Cd/haemoglobin affinity assay at 1 and 4 weeks post-Hp infection. Significance was determined by the Student's t-test or ANOVA followed by Tukey's LSD. Bacterial load was significantly increased (p<0.05) at 4 weeks (6x 106 CFU/g tissue; mean) post-Hp infection compared to 1 week (3 X 106 CFU/g tissue). MT levels (4.1 ± 0.2 nmol Cd bound/g tissue; mean ± sem) were significantly decreased (p<0.05) after 1 week of Hp infection compared to non-infected controls (5.7 ± 0.6 nmol Cd bound/g tissue). In addition, after 4 weeks of Hp infection MT levels were further depleted (2.9 ± 0.2 nmol Cd bound/g tissue) compared to non-infected controls (p<0.01). These findings suggest that MT degradation may be enhanced after sequestration of ROS or, alternatively, Hp infection may inhibit the endogenous expression of gastric MT. As the exact role of MT in relation to Hp infection is not fully understood, further work characterizing susceptibility to Hp infection in mice lacking MT expression may help elucidate its role.