Boric acid induces cytoplasmic stress granule formation, eIF2α phosphorylation, and ATF4 in prostate DU-145 cellsReportar como inadecuado

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, Volume 28, Issue 1, pp 133–141

First Online: 26 November 2014Received: 08 July 2014Accepted: 13 November 2014DOI: 10.1007-s10534-014-9809-5

Cite this article as: Henderson, K.A., Kobylewski, S.E., Yamada, K.E. et al. Biometals 2015 28: 133. doi:10.1007-s10534-014-9809-5


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 channel, and lowers endoplasmic reticulum ER Ca. Low ER Ca 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.

KeywordsBoron Boric acid eIF2α ATF4 DU-145 cells AbbreviationsBABoric acid

cADPRCyclic ADP ribose

EREndoplasmic reticulum

TIA-1T-cell intracellular antigen-1

Grp78Binding immunoglobulin protein BiP also known as 78 kDa glucose-regulated protein

ATF4Activating transcription factor 4

SGStress granule

ISRIntegrated stress response

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Autor: Kimberly A. Henderson - Sarah E. Kobylewski - Kristin E. Yamada - Curtis D. Eckhert


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