P-selectin expression has been shown inHelicobacter pylori-infected persons, an infection that has been clinically associated with platelet-related diseases, such as idiopathic thrombocytopenic purpura. However, the role of P-selectin expression during H pylori infection remains unclear. In this study, we hypothesized that P-selectin expression was associated with platelet aggregation during H pylori infection. Using flow cytometry, we examined the levels of adhesion between H pylori and platelets as well as the levels of P-selectin expression and platelet phosphatidylserine (PS) expression during H pylori infection. Significantly high levels of adhesion between proaggregatory bacteria and platelets were observed. We identified that H pylori IgG is required for bacteria to induce Pselectin expression and that a significant release of P-selectin is essential for H pylori to induce aggregation. In addition, cellular apoptotic signs, such as membrane blebbing, were observed in platelet aggregates. PS expression was also detected in platelets during infection with both pro-aggrogatory and nonaggregatory strains of H pylori. These results suggest that the decrease in platelet counts seen during H pylori infection is the result of P-selection-dependent platelet aggregation and PS expression induced by the bacteria. IntroductionMany diseases associated with platelet aggregation have been described as being related to Helicobacter pylori infection. For example, H pylori-infected persons have a tendency toward suffering from myocardial infarctions, 1-3 coronary heart disease, 4,5 and stroke. 6 It has also been suggested that H pylori may trigger the formation of thrombotic thrombocytopenic purpura (TTP) by inducing platelet aggregation through an interaction with the von Willebrand factor (VWF). 7 There have also been implications that chronic H pylori infection may be associated with idiopathic thrombocytopenic purpura (ITP), as eradication of the bacteria from gastric mucosa has shown improvement in some ITP patients. [8][9][10][11][12][13][14][15][16] There is ongoing interest in identifying the various H pylori virulence factors that may predict the risk of developing symptoms of ITP. Studies have primarily focused on 2 groups of putative bacterial virulence factors, the cag pathogenicity island (for which CagA is a marker) and the vacuolating cytotoxin, such as VacA 17,18 ; however, CagA and VacA have not been suggested to be causes of H pylori-induced platelet aggregation. 19 There has been evidence showing that associations exist between H pylori and platelet aggregation in vivo. Platelet aggregation was observed in rat gastric mucosal microcirculation in vivo after H pylori administration. 20 An increase in arterial thrombosis was also found in chronic H pylori-infected mice. 17 However, the mechanisms of how H pylori induces platelet aggregation are not clearly understood. Byrne et al proposed that the H pylori strain 60190 (ATCC 49503) induces platelet aggregation through interactions between H pylori, its ant...

It is known that Fas death domain-associated protein (Daxx) possesses both putative nuclear and cytoplasmic functions. However, the nuclear transport mechanism is largely unknown. This study examined the nuclear location signal (NLS) of Daxx and whether the nuclear transport of Daxx was mediated by small ubiquitin-related modifier (SUMO). Two NLS motifs of Daxx, leucine (L)-rich nuclear export signal (NES)-like motif (188IXXLXXLLXL197) and C-terminal lysine (K) rich NLS2 (amino acids 627-634) motif, were identified and the K630 and K631 on the NLS2 motif were characterized as the major sumoylation sites of Daxx by in vitro sumoylation analysis. Proteins of inactive SUMO (SUMO-delta), a sumoylation-incompetent mutant, and Daxx NLS mutants (Daxx-NES(mut) and Daxx NLS2(mut)) were dispersed in cytoplasm. The cytoplasmic dispersed Daxx mutants could be relocalized to nucleus by cotransfection with active SUMO, but not with inactive SUMO-delta, demonstrating the role of SUMO on regulating the cytoplasmonuclear transport of Daxx. However, inactive SUMO-delta could also be relocalized to nucleus during cotransfection with wild-type Daxx, suggesting that SUMO regulation of the cytoplasmonuclear transport of its target protein Daxx does not need covalent modification. This study shows that cytoplasmic SUMO has a biological role in enhancing the cytoplasmonuclear transport of its target protein Daxx and it may be done through the non-sumoylation interactions.

This work is the first to verify IL-1RN*2 as an independent factor that governs the development of duodenal ulcers. Our data indicate that H. pylori infection and IL-1RN*2 synergistically determine susceptibility to duodenal ulcer. The blood group phenotype is possibly a crucial determinant for the outcome of the impact of an interleukin-1 locus polymorphism on H. pylori-infected individuals.