32 research outputs found
Down-regulation of HSP70 sensitizes gastric epithelial cells to apoptosis and growth retardation triggered by H. pylori
<p>Abstract</p> <p>Background</p> <p><it>H. pylori </it>infection significantly attenuated the expression of HSP70 in gastric mucosal cells. However, the role of HSP70 cancellation in <it>H. pylori</it>-associated cell damages is largely unclear.</p> <p>Methods</p> <p>Small interfering RNA (siRNA) was used to down-regulate HSP70 in gastric epithelial cell lines AGS. The transfected cells were then incubated with <it>H. pylori </it>and the functions of HSP70 suppression were observed by viability assay, cell cycle analyses and TUNEL assay. HSP70 target apoptotic proteins were further identified by Western blot.</p> <p>Results</p> <p>The inhibition of HSP70 has further increased the effect of growth arrest and apoptosis activation triggered by <it>H. pylori </it>in gastric epithelial cells. The anti-proliferation function of HSP70 depletion was at least by up-regulating p21 and cell cycle modulation with S-phase accumulation. An increase of apoptosis-inducing factor (AIF) and cytosolic cytochrome C contributes to the activation of apoptosis following down-regulation of intracellular HSP70. Extracellular HSP70 increased cellular resistance to apoptosis by suppression the release of AIF and cytochrome c from mitochondria, as well as inhibition of p21 expression.</p> <p>Conclusions</p> <p>The inhibition of HSP70 aggravated gastric cellular damages induced by <it>H. pylori</it>. Induction of HSP70 could be a potential therapeutic target for protection gastric mucosa from <it>H. pylori</it>-associated injury.</p
Proteomics of Buccal Cavity Mucus in Female Tilapia Fish (Oreochromis spp.): A Comparison between Parental and Non-Parental Fish
Mouthbrooding is an elaborate form of parental care displayed by many teleost
species. While the direct benefits of mouthbrooding such as protection and
transportation of offsprings are known, it is unclear if mouthbrooding offers
additional benefits to embryos during incubation. In addition, mouthbrooding
could incur negative costs on parental fish, due to limited feeding
opportunities. Parental tilapia fish (Oreochromis spp.) display
an elaborated form of parental care by incubating newly hatched embryos in oral
buccal cavity until the complete adsorption of yolk sac. In order to understand
the functional aspects of mouthbrooding, we undertake a proteomics approach to
compare oral mucus sampled from mouthbrooders and non-mouthbrooders,
respectively. Majority of the identified proteins have also been previously
identified in other biological fluids or mucus-rich organs in different
organisms. We also showed the upregulation of 22 proteins and down regulation of
3 proteins in mucus collected from mouthbrooders. Anterior gradient protein,
hemoglobin beta-A chain and alpha-2 globin levels were lower in mouthbrooder
samples. Mouthbrooder oral mucus collectively showed increase levels of proteins
related to cytoskeletal properties, glycolytic pathway and mediation of
oxidative stress. Overall the findings suggest cellular stress response,
probably to support production of mucus during mouthbrooding phase
Effect of acute administration of sildenafil to rats with detrusor overactivity induced by chronic deficiency of nitric oxide
Effects of leminoprazole, omeprazole and sucralfate on indomethacininduced delayed healing of kissing gastric ulcers in rats
The mechanism by which indomethacin delays healing of gastric ulcers induced in rats: Role of neutrophils
Acetic acid ulcers: a new method for producing solitary chronic ulcers in rat stomachs by intraluminal application of acetic acid solution
Endogenous nitric oxide proves not to be involved in the inhibition by IL-1beta of TGF-alpha-stimulated proliferation of RGM1 cells
Involvement of heat shock proteins in the healing of acetic acid-induced gastric ulcers in rats
Effects and sites of action of a M1 receptor positive allosteric modulator on colonic motility in rats and dogs compared with 5-HT4 agonism and cholinesterase inhibition
BACKGROUND: Muscarinic receptor 1 positive allosteric modulators (M1PAMs) enhance colonic propulsive contractions and defecation through the facilitation of M1 receptor (M1R)-mediated signaling. We examined M1R expression in the colons of 5 species and compared colonic propulsion and defecation caused by the M1PAM, T440, the 5-HT4 agonist, prucalopride, and the cholinesterase inhibitor, neostigmine, in rats and dogs. METHODS: M1R expression was profiled by immunostaining and in situ hybridization. In vivo studies utilized male SD rats and beagle dogs. Colonic propulsive contractions were recorded by manometry in anesthetized rats. Gut contractions in dogs were assessed using implanted force transducers in the ileum, proximal, mid, and distal colons. KEY RESULTS: M1R was localized to neurons of myenteric and submucosal plexuses and the epithelium of the human colon. A similar receptor localization was observed in rat, dog, mouse, and pig. T440 enhanced normal defecation in rats in a dose-dependent manner. Prucalopride also enhanced defecation in rats, but the maximum effect was half that of T440. Neostigmine and T440 were similarly effective in enhancing defecation, but the effective dose of neostigmine was close to its lethal dose. In rats, all 3 compounds induced colonic contractions, but the associated propulsion was strongest with T440. In dogs, intestinal contractions elicited by T440 propagated from ileum to distal colon. Prucalopride and neostigmine also induced intestinal contractions, but these were less well coordinated. No loss of effectiveness of T440 on defecation occurred after 5 days of repeated dosing. CONCLUSION AND INFERENCES: These results suggest that M1PAMs produce highly coordinated propagating contraction by actions on the enteric nervous system of the colon. The localization of M1R to enteric neurons in both animals and humans suggests that the M1PAM effects would be translatable to human. M1PAMs provide a potential novel therapeutic option for constipation disorders.Yasuhiro Tsukimi, Ruslan V. Pustovit, Andrea M. Harrington, Sonia Garcia-Caraballo, Stuart M. Brierley, Madeleine Di Natale, Juan C. Molero, John B. Furnes