Anders Øverby

Allyl isothiocyanate depletes glutathione and upregulates expression of glutathione S-transferases in Arabidopsis thaliana

Allyl isothiocyanate (AITC) is a phytochemical associated with plant defense in plants from the Brassicaceae family. AITC has long been recognized as a countermeasure against external threats, but recent reports suggest that AITC is also involved in the onset of defense-related mechanisms such as the regulation of stomatal aperture. However, the underlying cellular modes of action in plants remain scarcely investigated. Here we report evidence of an AITC-induced depletion of glutathione (GSH) and the effect on gene expression of the detoxification enzyme family glutathione S-transferases (GSTs) in Arabidopsis thaliana. Treatment of A. thaliana wild-type with AITC resulted in a time- and dose-dependent depletion of cellular GSH. AITC-exposure of mutant lines vtc1 and pad2-1 with elevated and reduced GSH-levels, displayed enhanced and decreased AITC-tolerance, respectively. AITC-exposure also led to increased ROS-levels in the roots and loss of chlorophyll which are symptoms of oxidative stress. Following exposure to AITC, we found that GSH rapidly recovered to the same level as in the control plant, suggesting an effective route for replenishment of GSH or a rapid detoxification of AITC. Transcriptional analysis of genes encoding GSTs showed an upregulation in response to AITC. These findings demonstrate cellular effects by AITC involving a reversible depletion of the GSH-pool, induced oxidative stress, and elevated expression of GST-encoding genes.

Mouse Models for Assessing the Protective Efficacy of Lactobacillus gasseri SBT2055 against Helicobacter suis Infection Associated with the Development of Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

Helicobacter suis strain TKY infection has been strongly associated with the development of gastric mucosa‐associated lymphoid tissue (MALT) lymphoma in a C57BL/6J mouse model.

In the Aftermath of Helicobacter pylori: Other Helicobacters Rising Up to Become the Next Gastric Epidemic?

Non-Helicobacter pylori-Helicobacters including H. suis, H. heilmanniisensu stricto and H. felis comprise a group of bacteria that may inhabit the stomach of humans and animals. Human gastric infection has been associated with gastritis, ulcer, MALT lymphoma and cancer. Although the fastidious nature of these organisms has hampered their research, recent advancements in in vitro cultivation and recent reports on in vivo models and prevalence studies in humans suggest this group of bacteria to be of more clinical significance than earlier believed. The present review discusses their history, microbiology and relevance to human health.

Allyl Isothiocyanate Inhibits Actin-Dependent Intracellular Transport in Arabidopsis thaliana

Volatile allyl isothiocyanate (AITC) derives from the biodegradation of the glucosinolate sinigrin and has been associated with growth inhibition in several plants, including the model plant Arabidopsis thaliana. However, the underlying cellular mechanisms of this feature remain scarcely investigated in plants. In this study, we present evidence of an AITC-induced inhibition of actin-dependent intracellular transport in A. thaliana. A transgenic line of A. thaliana expressing yellow fluorescent protein (YFP)-tagged actin filaments was used to show attenuation of actin filament movement by AITC. This appeared gradually in a time- and dose-dependent manner and resulted in actin filaments appearing close to static. Further, we employed four transgenic lines with YFP-fusion proteins labeling the Golgi apparatus, endoplasmic reticulum (ER), vacuoles and peroxisomes to demonstrate an AITC-induced inhibition of actin-dependent intracellular transport of or, in these structures, consistent with the decline in actin filament movement. Furthermore, the morphologies of actin filaments, ER and vacuoles appeared aberrant following AITC-exposure. However, AITC-treated seedlings of all transgenic lines tested displayed morphologies and intracellular movements similar to that of the corresponding untreated and control-treated plants, following overnight incubation in an AITC-absent environment, indicating that AITC-induced decline in actin-related movements is a reversible process. These findings provide novel insights into the cellular events in plant cells following exposure to AITC, which may further expose clues to the physiological significance of the glucosinolate-myrosinase system.

Allyl isothiocyanate affects the cell cycle of Arabidopsis thaliana

Isothiocyanates (ITCs) are degradation products of glucosinolates present in members of the Brassicaceae family acting as herbivore repellents and antimicrobial compounds. Recent results indicate that allyl ITC (AITC) has a role in defense responses such as glutathione depletion, ROS generation and stomatal closure. In this study we show that exposure to non-lethal concentrations of AITC causes a shift in the cell cycle distribution of Arabidopsis thaliana leading to accumulation of cells in S-phases and a reduced number of cells in non-replicating phases. Furthermore, transcriptional analysis revealed an AITC-induced up-regulation of the gene encoding cyclin-dependent kinase A while several genes encoding mitotic proteins were down-regulated, suggesting an inhibition of mitotic processes. Interestingly, visualization of DNA synthesis indicated that exposure to AITC reduced the rate of DNA replication. Taken together, these results indicate that non-lethal concentrations of AITC induce cells of A. thaliana to enter the cell cycle and accumulate in S-phases, presumably as a part of a defensive response. Thus, this study suggests that AITC has several roles in plant defense and add evidence to the growing data supporting a multifunctional role of glucosinolates and their degradation products in plants.

Plant phytochemicals: potential anticancer agents against gastric cancer.

Isothiocyanates (ITCs) are plant phytochemicals derived from vegetables consumed by human. ITCs comprise potent anti-carcinogenic agents of which the consumption has been linked to a reduced risk of cancer at several locations in the body. However, the studies on coping with gastric cancer remain unsatisfied. In the present review, ITCs are discussed in this context as ITCs may target gastric tumorigenesis at multiple levels. ITCs are taken up in the stomach, exposing mucosal and muscle layer cells as well as affecting Helicobacter pylori residing in the stomach. The natural and potent anti-cancer ITCs from vegetables have a great potential against gastric cancer, a disease in need of new treatment or preventive modalities.

Allyl-isothiocyanate treatment induces a complex transcriptional reprogramming including heat stress, oxidative stress and plant defence responses in Arabidopsis thaliana

BackgroundIsothiocyanates (ITCs) are degradation products of the plant secondary metabolites glucosinolates (GSLs) and are known to affect human health as well as plant herbivores and pathogens. To investigate the processes engaged in plants upon exposure to isothiocyanate we performed a genome scale transcriptional profiling of Arabidopsis thaliana at different time points in response to an exogenous treatment with allyl-isothiocyanate.ResultsThe treatment triggered a substantial response with the expression of 431 genes affected (P < 0.05 and log2 ≥ 1 or ≤ -1) already after 30 min and that of 3915 genes affected after 9 h of exposure, most of the affected genes being upregulated. These are involved in a considerable number of different biological processes, some of which are described in detail: glucosinolate metabolism, sulphate uptake and assimilation, heat stress response, oxidative stress response, elicitor perception, plant defence and cell death mechanisms.ConclusionExposure of Arabidopsis thaliana to vapours of allyl-isothiocyanate triggered a rapid and substantial transcriptional response affecting numerous biological processes. These include multiple stress stimuli such as heat stress response and oxidative stress response, cell death and sulphur secondary defence metabolism. Hence, effects of isothiocyanates on plants previously reported in the literature were found to be regulated at the gene expression level. This opens some avenues for further investigations to decipher the molecular mechanisms underlying the effects of isothiocyanates on plants.

Naturally occurring phenethyl isothiocyanate-induced inhibition of gastric cancer cell growth by disruption of microtubules

Phenethyl isothiocyanate (PEITC) derives from vegetables commonly consumed by man and has been demonstrated as a promising chemopreventive agent against several types of cancer. However, the potential in preventing gastric cancer as well as the underlying mechanisms are to date not fully understood. The present study aimed at elucidating the cellular effects induced by PEITC in gastric cancer cells leading to apoptosis.

Evidence for a primate origin of zoonotic Helicobacter suis colonizing domesticated pigs

Helicobacter suis is the second most prevalent Helicobacter species in the stomach of humans suffering from gastric disease. This bacterium mainly inhabits the stomach of domesticated pigs, in which it causes gastric disease, but it appears to be absent in wild boars. Interestingly, it also colonizes the stomach of asymptomatic rhesus and cynomolgus monkeys. The origin of modern human-, pig- or non-human primate-associated H. suis strains in these respective host populations was hitherto unknown. Here we show that H. suis in pigs possibly originates from non-human primates. Our data suggest that a host jump from macaques to pigs happened between 100 000 and 15 000 years ago and that pig domestication has had a significant impact on the spread of H. suis in the pig population, from where this pathogen occasionally infects humans. Thus, in contrast to our expectations, H. suis appears to have evolved in its main host in a completely different way than its close relative Helicobacter pylori in humans.

Prevalence of Gastric Non-Helicobacter pylori-Helicobacters in Japanese Patients with Gastric Disease

Background: Non-Helicobacter pylori-helicobacters (NHPH) compose a group of gram negative zoonotic bacteria that may induce in humans gastric diseases including gastritis, gastroduodenal ulcer and MALT lymphoma. Their prevalence in the general population has previously been reported to 0.1-6.2%, although such reports still remain less in number. Aims: This study aimed at estimating the prevalence of gastric NHPH in Japanese people, and further aimed at linking this to different gastric diseases and co-infection with H. pylori. Methods: Endoscopically obtained biopsy samples from 280 Japanese patients with various gastric diseases were collected. Samples were analyzed by immunohistochemistry and by species-specific PCR for detection of gastric helicobacters. Results: The total prevalence of gastric NHPH among 280 Japanese patients was 6.1%, and the prevalence of H. pylori was 65.7%. There was no significant difference in prevalence of either NHPH or H. pylori when infected with H. pylori or NHPH, respectively. NHPH infection was found to be the highest in patients with gastric MALT lymphoma and duodenal ulcer, the former being independent of co-infection with H. pylori and the latter being dependent. Conclusions: This study reports a total prevalence of 6.1% of gastric NHPH in Japanese patients, and further highlights gastric MALT lymphoma and duodenal ulcer (when co-infected with H. pylori) as important related diseases.