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Boric acid induces cytoplasmic stress granule formation, eIF2α phosphorylation, and ATF4 in prostate DU-145 cells.

Henderson KA, Kobylewski SE, Yamada KE, Eckhert CD - Biometals (2014)

Bottom Line: Low ER [Ca(2+)] has been reported to induce ER stress and activate the eIF2α/ATF4 pathway.Mild activation of eIF2α and its downstream transcription factor, ATF4, enables cells to reconfigure gene expression to manage stress conditions and mild activation of ATF4 is also required for the differentiation of osteoblast cells.Our results using physiological levels of boric acid identify the eIF2α/ATF pathway as a plausible mode of action that underpins the reported health effects of dietary boron.

View Article: PubMed Central - PubMed

Affiliation: Interdepartmental Program in Molecular Toxicology, University of California, Los Angeles, CA, USA.

ABSTRACT
Dietary boron intake is associated with reduced prostate and lung cancer risk and increased bone mass. Boron is absorbed and circulated as boric acid (BA) and at physiological concentrations is a reversible competitive inhibitor of cyclic ADP ribose, the endogenous agonist of the ryanodine receptor calcium (Ca(+2)) channel, and lowers endoplasmic reticulum (ER) [Ca(2+)]. Low ER [Ca(2+)] has been reported to induce ER stress and activate the eIF2α/ATF4 pathway. Here we report that treatment of DU-145 prostate cells with physiological levels of BA induces ER stress with the formation of stress granules and mild activation of eIF2α, GRP78/BiP, and ATF4. Mild activation of eIF2α and its downstream transcription factor, ATF4, enables cells to reconfigure gene expression to manage stress conditions and mild activation of ATF4 is also required for the differentiation of osteoblast cells. Our results using physiological levels of boric acid identify the eIF2α/ATF pathway as a plausible mode of action that underpins the reported health effects of dietary boron.

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Related in: MedlinePlus

BA induces ER vacuolization and expansion in DU-145 cells. TEM images of DU-145 cells treated for 24 h with 0, 10, 50, and 250 µM BA (n = 3). Cells exhibited a dose-dependent swelling and vacuolization of the ER, (N nucleus, ER endoplasmic reticulum). White boxes indicate magnified area shown on the right
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Fig1: BA induces ER vacuolization and expansion in DU-145 cells. TEM images of DU-145 cells treated for 24 h with 0, 10, 50, and 250 µM BA (n = 3). Cells exhibited a dose-dependent swelling and vacuolization of the ER, (N nucleus, ER endoplasmic reticulum). White boxes indicate magnified area shown on the right

Mentions: Light microscopy analysis of BA treated DU-145 cells showed cell flattening (Barranco and Eckhert 2006), therefore we were interested in knowing how this morphological change manifested at the ultrastructural level. We used TEM on DU-145 cells treated for 24 h with 0, 10, 50 or 250 µM BA. The results show a dose-dependent increase in ER expansion, cytoplasmic granularity and cytoplasmic vacuole formation (Fig. 1).Fig. 1


Boric acid induces cytoplasmic stress granule formation, eIF2α phosphorylation, and ATF4 in prostate DU-145 cells.

Henderson KA, Kobylewski SE, Yamada KE, Eckhert CD - Biometals (2014)

BA induces ER vacuolization and expansion in DU-145 cells. TEM images of DU-145 cells treated for 24 h with 0, 10, 50, and 250 µM BA (n = 3). Cells exhibited a dose-dependent swelling and vacuolization of the ER, (N nucleus, ER endoplasmic reticulum). White boxes indicate magnified area shown on the right
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4300416&req=5

Fig1: BA induces ER vacuolization and expansion in DU-145 cells. TEM images of DU-145 cells treated for 24 h with 0, 10, 50, and 250 µM BA (n = 3). Cells exhibited a dose-dependent swelling and vacuolization of the ER, (N nucleus, ER endoplasmic reticulum). White boxes indicate magnified area shown on the right
Mentions: Light microscopy analysis of BA treated DU-145 cells showed cell flattening (Barranco and Eckhert 2006), therefore we were interested in knowing how this morphological change manifested at the ultrastructural level. We used TEM on DU-145 cells treated for 24 h with 0, 10, 50 or 250 µM BA. The results show a dose-dependent increase in ER expansion, cytoplasmic granularity and cytoplasmic vacuole formation (Fig. 1).Fig. 1

Bottom Line: Low ER [Ca(2+)] has been reported to induce ER stress and activate the eIF2α/ATF4 pathway.Mild activation of eIF2α and its downstream transcription factor, ATF4, enables cells to reconfigure gene expression to manage stress conditions and mild activation of ATF4 is also required for the differentiation of osteoblast cells.Our results using physiological levels of boric acid identify the eIF2α/ATF pathway as a plausible mode of action that underpins the reported health effects of dietary boron.

View Article: PubMed Central - PubMed

Affiliation: Interdepartmental Program in Molecular Toxicology, University of California, Los Angeles, CA, USA.

ABSTRACT
Dietary boron intake is associated with reduced prostate and lung cancer risk and increased bone mass. Boron is absorbed and circulated as boric acid (BA) and at physiological concentrations is a reversible competitive inhibitor of cyclic ADP ribose, the endogenous agonist of the ryanodine receptor calcium (Ca(+2)) channel, and lowers endoplasmic reticulum (ER) [Ca(2+)]. Low ER [Ca(2+)] has been reported to induce ER stress and activate the eIF2α/ATF4 pathway. Here we report that treatment of DU-145 prostate cells with physiological levels of BA induces ER stress with the formation of stress granules and mild activation of eIF2α, GRP78/BiP, and ATF4. Mild activation of eIF2α and its downstream transcription factor, ATF4, enables cells to reconfigure gene expression to manage stress conditions and mild activation of ATF4 is also required for the differentiation of osteoblast cells. Our results using physiological levels of boric acid identify the eIF2α/ATF pathway as a plausible mode of action that underpins the reported health effects of dietary boron.

Show MeSH
Related in: MedlinePlus