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Geranylgeranylacetone selectively binds to the HSP70 of Helicobacter pylori and alters its coccoid morphology.

Grave E, Yokota S, Yamamoto S, Tamura A, Ohtaki-Mizoguchi T, Yokota K, Oguma K, Fujiwara K, Ogawa N, Okamoto T, Otaka M, Itoh H - Sci Rep (2015)

Bottom Line: GGA-treated cells elicited enhanced interleukin-8 production by gastric cancer cell lines and potentiated susceptibility to complement as compared to untreated cells.This morphological conversion by GGA resulted in accelerated growth of H. pylori.These results suggest a model in which GGA sensitizes H. pylori to antibiotic treatment by converting the cells to an actively growing state.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Science, Graduate School and Faculty of Engineering Science, Akita University, Akita 010-8502, Japan.

ABSTRACT
Geranylgeranylacetone (GGA) is used to treat patients suffering from peptic ulcers and gastritis. We examined the effect of GGA on Helicobacter pylori, which is a causative factor of gastrointestinal diseases. Previously, we have reported that GGA binds specifically to the molecular chaperone HSP70. In this paper, we report that GGA bounds to H. pylori HSP70 (product of the DnaK gene) with 26-times higher affinity than to human HSP70, and induced large conformational changes as observed from surface plasmon resonance and circular dichroism. Binding of GGA suppressed the activity of the H. pylori chaperone. GGA also altered several characteristics of H. pylori cells. GGA-treated cells elicited enhanced interleukin-8 production by gastric cancer cell lines and potentiated susceptibility to complement as compared to untreated cells. GGA also caused morphological alterations in H. pylori as reflected in fewer coccoid-like cells, suggesting that GGA converts H. pylori to an actively dividing, spiral state (vegetative form) from a non-growing, coccoid state. This morphological conversion by GGA resulted in accelerated growth of H. pylori. These results suggest a model in which GGA sensitizes H. pylori to antibiotic treatment by converting the cells to an actively growing state.

No MeSH data available.


Related in: MedlinePlus

Effect of GGA on Interleukin-8 (IL-8) production induced by H. pylori live cells in gastric carcinoma cell line MKN28 and MKN45.H. pylori SS1 was precultured in the absence or presence of GGA at a concentration of 0 (open circle), 1 (closed red diamond), and 5 (closed black square) mM. The resulting cells were inoculated to MKN28 cells or MKN45 cells at MOI 10 or 100. After 24 h incubation, IL-8 in the culture supernatant was measured by ELISA. Each experiment was performed in triplicate.
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f8: Effect of GGA on Interleukin-8 (IL-8) production induced by H. pylori live cells in gastric carcinoma cell line MKN28 and MKN45.H. pylori SS1 was precultured in the absence or presence of GGA at a concentration of 0 (open circle), 1 (closed red diamond), and 5 (closed black square) mM. The resulting cells were inoculated to MKN28 cells or MKN45 cells at MOI 10 or 100. After 24 h incubation, IL-8 in the culture supernatant was measured by ELISA. Each experiment was performed in triplicate.

Mentions: We examined effect of GGA pretreatment of H. pylori cells on their induction of IL-8 in gastric carcinoma cell lines, MKN28 and MKN45. IL-8 is the most important chemokine produced by epithelial cells for the inflammatory response induction and pathogenesis of H. pylori26. GGA pretreatment decreased the ability of H. pylori to induce IL-8 in both cancer cell lines (Fig. 8).


Geranylgeranylacetone selectively binds to the HSP70 of Helicobacter pylori and alters its coccoid morphology.

Grave E, Yokota S, Yamamoto S, Tamura A, Ohtaki-Mizoguchi T, Yokota K, Oguma K, Fujiwara K, Ogawa N, Okamoto T, Otaka M, Itoh H - Sci Rep (2015)

Effect of GGA on Interleukin-8 (IL-8) production induced by H. pylori live cells in gastric carcinoma cell line MKN28 and MKN45.H. pylori SS1 was precultured in the absence or presence of GGA at a concentration of 0 (open circle), 1 (closed red diamond), and 5 (closed black square) mM. The resulting cells were inoculated to MKN28 cells or MKN45 cells at MOI 10 or 100. After 24 h incubation, IL-8 in the culture supernatant was measured by ELISA. Each experiment was performed in triplicate.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4561889&req=5

f8: Effect of GGA on Interleukin-8 (IL-8) production induced by H. pylori live cells in gastric carcinoma cell line MKN28 and MKN45.H. pylori SS1 was precultured in the absence or presence of GGA at a concentration of 0 (open circle), 1 (closed red diamond), and 5 (closed black square) mM. The resulting cells were inoculated to MKN28 cells or MKN45 cells at MOI 10 or 100. After 24 h incubation, IL-8 in the culture supernatant was measured by ELISA. Each experiment was performed in triplicate.
Mentions: We examined effect of GGA pretreatment of H. pylori cells on their induction of IL-8 in gastric carcinoma cell lines, MKN28 and MKN45. IL-8 is the most important chemokine produced by epithelial cells for the inflammatory response induction and pathogenesis of H. pylori26. GGA pretreatment decreased the ability of H. pylori to induce IL-8 in both cancer cell lines (Fig. 8).

Bottom Line: GGA-treated cells elicited enhanced interleukin-8 production by gastric cancer cell lines and potentiated susceptibility to complement as compared to untreated cells.This morphological conversion by GGA resulted in accelerated growth of H. pylori.These results suggest a model in which GGA sensitizes H. pylori to antibiotic treatment by converting the cells to an actively growing state.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Science, Graduate School and Faculty of Engineering Science, Akita University, Akita 010-8502, Japan.

ABSTRACT
Geranylgeranylacetone (GGA) is used to treat patients suffering from peptic ulcers and gastritis. We examined the effect of GGA on Helicobacter pylori, which is a causative factor of gastrointestinal diseases. Previously, we have reported that GGA binds specifically to the molecular chaperone HSP70. In this paper, we report that GGA bounds to H. pylori HSP70 (product of the DnaK gene) with 26-times higher affinity than to human HSP70, and induced large conformational changes as observed from surface plasmon resonance and circular dichroism. Binding of GGA suppressed the activity of the H. pylori chaperone. GGA also altered several characteristics of H. pylori cells. GGA-treated cells elicited enhanced interleukin-8 production by gastric cancer cell lines and potentiated susceptibility to complement as compared to untreated cells. GGA also caused morphological alterations in H. pylori as reflected in fewer coccoid-like cells, suggesting that GGA converts H. pylori to an actively dividing, spiral state (vegetative form) from a non-growing, coccoid state. This morphological conversion by GGA resulted in accelerated growth of H. pylori. These results suggest a model in which GGA sensitizes H. pylori to antibiotic treatment by converting the cells to an actively growing state.

No MeSH data available.


Related in: MedlinePlus