<i>Helicobacter pylori</i>upregulates prion protein expression in gastric mucosa: A possible link to prion disease

Konturek, Peter C.; Bazela, Karolina; Kukharskyy, Vitaliy; Bauer, Michael; Hahn, Eckhart G.; Schuppan, Detlef

doi:10.3748/wjg.v11.i48.7651

Cited by 24 publications

(14 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the S. Tm infected mice, PrP C expression was increased by 3-fold in the caecum and increased by approximately 1.5-fold in the draining MLN, consistent with increased PrP C expression detected in the stomach of humans with Helicobacter -induced gastritis [40]. Since PrP C expression directly correlates with incubation period, or the time from prion inoculation to development of terminal scrapie [41], the elevated PrP C expression in the caecum may lead to increased PrP conversion and accelerated prion transport and neuroinvasion.…”

Section: Discussionsupporting

confidence: 54%

Bacterial Colitis Increases Susceptibility to Oral Prion Disease

et al. 2009

View full text Add to dashboard Cite

Dietary exposure to prion-contaminated materials has caused kuru and variant Creutzfeldt-Jakob disease in humans, and transmissible spongiform encephalopathies (TSEs) of cattle, mink, and felines. The epidemiology of dietary prion infections suggest that host genetic modifiers, and possibly exogenous cofactors, may play a decisive role in determining disease susceptibility. However, few cofactors influencing prion susceptibility have been identified. Here we investigated whether colitis might represent one such cofactor. We report that moderate colitis caused by an attenuated strain of Salmonella more than doubles the susceptibility of mice to oral prion infection, and modestly accelerates the development of disease after prion challenge. The prion protein was upregulated in intestines and mesenteric lymph nodes of mice with colitis, providing a possible mechanism for the impact of colitis onto prion pathogenesis. Therefore, moderate intestinal inflammation at the time of prion exposure may constitute one of the elusive risk factors underlying the development of TSE.

show abstract

Section: Discussionsupporting

confidence: 54%

Bacterial Colitis Increases Susceptibility to Oral Prion Disease

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Pammer et al (9) found that the expression of PrP C was negative or weak in the neck region of gastric mucosa but was up-regulated in the mucosa of patients infected with Helicobacter pylori (Hp). Recent work (10) confirmed the result and further proved that up-regulation of gastric PrP C expression by Hp infection was linked to Hp-induced hypergastrinemia. Since Hp infection is thought to play an important role in carcinogenesis of gastric mucosa, it is interesting to investigate the relationship between PrP C and gastric cancer.…”

mentioning

confidence: 55%

“…Role of PrP C in against oxidative stress and serum deprivation have also been intensively studied (5,6). In addition to the nervous system, PrP C is also expressed in the mucosa of gastrointestinal tract (23), especially in the case of Hp infection (10). Our previous studies showed that PrP C was overexpressed in gastric cancer tissues and correlated with tumor histological types and TNM stages (12,13).…”

Section: Discussionmentioning

confidence: 99%

Cellular prion protein promotes proliferation and G1/S transition of human gastric cancer cells SGC7901 and AGS

et al. 2007

View full text Add to dashboard Cite

The function of cellular prion protein (PrP(C)), the essential protein for the pathogenesis and transmission of prion diseases, is still largely unknown. The putative roles of PrP(C) are thought to be related to cell signaling, survival, and differentiation. In a previous study, we showed that PrP(C) was overexpressed in gastric cancer tissues. In the present report, we show that ectopic expression of PrP(C) could promote tumorigenesis, proliferation, and G1/S transition in gastric cancer cells. Furthermore, CyclinD1, a protein related to cell cycle, was shown to be significantly up-regulated by PrP(C) at both mRNA and protein levels. PI3K/Akt pathway mediated above PrP(C) signal since PrP(C) increased the expression of phosphorylated Akt, and the specific inhibitor of Akt, LY294002, could markedly suppress growth of SGC7901 and transactivation of CyclinD1 induced by PrP(C). Octapeptide repeat region played a vital role in this function, as deletion of this region abolished or reduced these effects. Collectively, this study demonstrates that overexpression of PrP(C) might promote the tumorigenesis and proliferation of gastric cancer cells at least partially through activation of PI3K/Akt pathway and subsequent transcriptional activation of CyclinD1 to regulate the G1/S phase transition, in which octapeptide repeat region might be an indispensable region.

show abstract

“…Infection by Helicobacter pylori significantly upregulates PrP C expression, and may be an important factor in human susceptibility to infectious prions in contaminated food [45].…”

Section: Functional Dynamics and Environmental Vulnerability Of Prpmentioning

confidence: 99%

Prion Stability and Infectivity in the Environment

Wiggins

2008

Neurochem Res

View full text Add to dashboard Cite

The biology of normal prion protein and the property of infectivity observed in abnormal folding conformations remain thinly characterized. However, enough is known to understand that prion proteins stretch traditional views of proteins in biological systems. Numerous investigators are resolving details of the novel mechanism of infectivity, which appears to feature a protein-only, homologous replication of misfolded isoforms. Many other features of prion biology are equally extraordinary. This review focuses on the status of infectious prions in various natural and man-made environments. The picture that emerges is that prion proteins are durable under extreme conditions of environmental exposure that are uncommon in biological phenomena, and this durability offers the potential for environmental reservoirs of persistent infectivity lasting for years. A recurrent theme in prion research is a propensity for these proteins to bind to mineral and metal surfaces, and several investigators have provided evidence that the normal cellular functions of prion protein may include metalloprotein interactions. This structural propensity for binding to mineral and metal ions offers the hypothesis that prion polypeptides are intrinsically predisposed to non-physiological folding conformations that would account for their environmental durability and persistent infectivity. Similarly, the avidity of binding and potency of prion infectivity from environmental sources also offers a recent hypothesis that prion polypeptides bound to soil minerals are actually more infectious than studies with purified polypeptides would predict. Since certain of the prion diseases have a history of epidemics in economically important animal species and have the potential to transmit to humans, urgency is attached to understanding the environmental transmission of prion diseases and the development of protocols for their containment and inactivation.

show abstract

Helicobacter pyloriupregulates prion protein expression in gastric mucosa: A possible link to prion disease

Abstract: H pylori infection leads to the upregulation of gastric PrPc expression. This can be linked to H pylori induced hypergastrinemia and increased mucosal PGE(2) and IL-1beta synthesis. H pylori creates a milieu for enhanced propagation of prions in the gastrointestinal tract.

Cited by 24 publications

References 35 publications

Bacterial Colitis Increases Susceptibility to Oral Prion Disease

Bacterial Colitis Increases Susceptibility to Oral Prion Disease

Cellular prion protein promotes proliferation and G1/S transition of human gastric cancer cells SGC7901 and AGS

Prion Stability and Infectivity in the Environment

Contact Info

Product

Resources

About