Boron

Boron both upregulates and inhibits Nrf2 - depends on the dose

Our results revealed that low doses of boron (up to 160 mg) had positive effect, while high doses (especially 640 mg) caused negative effect on the development of the kidney. The cellular apoptosis was in a biphasic manner by altering the boron quantities.

The low doses regulate the oxidative and enzyme activity in the kidney. The IHC and western blot showed maximum localization of Nrf2 in 80 mg/L BA dose group. Furthermore, supplementation of boron at low doses upregulated the expression of genes involved in the antioxidant pathway.

Taken together, the study demonstrated that low levels of boron (up to 160 mg) inhibited the cell apoptosis, regulate the enzyme activity, and improved the antioxidant system, thus may encourage the development of the ostrich chick’s kidney, while a high amount of boron especially 640 mg/L promoted cell apoptosis and reduced the antioxidant capacity, thus caused negative effect to the ostrich chick’s kidney. (R1)

• Low dose of boron upregulates Nrf2
• Higher doses of boron reduce antioxidant capacity

Boron activates eIF2a via PERK

Treatment of DU-145 human prostate cancer cells with 10 μM BA stimulates phosphorylation of elongation initiation factor 2α (eIF2α) at Ser51 leading to activation of the eIF2α/ATF4 pathway which activates the DNA damage-inducible protein GADD34. … DU-145 cells were treated with 10 μM BA and Nrf2 measured by immunofluorescence. Cytoplasmic Nrf2 was translocated to the nucleus at 1.5-2 h in DU-145 and MEF WT cells, but not MEF PERK -/- cells. … The BA signaling pathway can be expressed using the schematic [BA + cADPR → cADPR-BA → [[ER]i Ca2+↓] → 3 pathways: PERK/eIF2αP → pathways ATF4 and Nrf2; and [[ER]i Ca2+↓] → ER stress → ATF6 pathway.

This signaling pathway provides a framework that links many of the molecular changes that underpin the biological effects of boron intake. (R2)

eIF2a is essential in UPR

PERK phosphorylates eIF2α at serine 51, thereby controlling the initiation step of protein synthesis and subsequently preventing an overload of proteins in the ER lumen.

Paradoxically, eIF2α phosphorylation via PERK increases the synthesis of transcription factors that contain upstream open reading frames (uORFs) in the 5’UTR of their mRNAs, including activating transcription factor 4 (ATF4), which is involved in the expression of several UPR target genes.

However, when ER stress is sustained and the adaptive mechanisms of the UPR are not sufficient to recover cellular protein homeostasis, a switch to pro-apoptotic signals triggers the death of damaged cells (R3)