Post-treatment with apocynin at a lower dose regulates the UPR branch of eIF2α and XBP-1 pathways after stroke.

Stroke leads to disturbance in the physiology of the ER (Endoplasmic Reticulum) that triggers UPR (Unfolded Protein Response) pathways aimed to compensate neuronal cell damage. However, sustained UPR causes stressful conditions in the ER lumen forming abnormal protein aggregates. Stroke-induced oxidative stress also amalgamates with UPR to safeguard and ensure the proper functioning of brain cells. Thus we tested the effect of apocynin (a potent antioxidant) post-treatment in experimental stroke on the outcome of ER stress and UPR branch pathways. We administered a low dose of apocynin at 1 mg/kg (intraperitoneal) to adult Sprague-Dawley rats subjected to Middle Cerebral Artery Occlusion (MCAO) for two-time points. The first dose immediately after re-establishing the blood flow and another at 6 h of reperfusion. Apocynin post-treatment significantly reduced ROS (Reactive Oxygen Species) generation at an early reperfusion time point of 4 h. It preserved neuronal morphology, dendritic spine density, reduced protein aggregation, and brain damage after 24 h of reperfusion. Apocynin post-treatment regulates the two UPR branch pathways in our experimental paradigm. 1) Down-regulation of eIF2α (Eukaryotic Initiation Factor 2α) phosphorylation, and CHOP (C/EBP homologous protein) 2) by reducing the XBP-1 (X-Box binding Protein-1) mRNA splicing downstream to PERK (Protein Kinase RNA-Like ER Kinase) and IRE1α (Inositol Requiring Enzyme 1alpha) UPR pathways, respectively. Bioinformatics prediction showed that apocynin has binding sites for PERK (Protein Kinase RNA-Like ER Kinase) and IRE1α proteins. The amino acid residues interacting with apocynin were Cys891 and Gln889 (for PERK), and the amino acids Ser726, Arg722, and Ala719 (for IRE1α) lying within their activation loop. Overall, these studies indicate that apocynin post-treatment might regulate ER stress/UPR pathways and minimize stroke brain damage, thus having implications for developing newer strategies for stroke treatment.

Correlation between serum trace elements and risk of preeclampsia: A case controlled study in Riyadh, Saudi Arabia.

Preeclampsia is a serious medical complication during pregnancy. In response to an increasing number of preeclamptic cases and scarcity of data concerning the interrelation between trace element levels and preeclampsia, we carried out a hospital based case-control study in Riyadh, Saudi Arabia to study the correlation between levels of serum trace elements and risk of preeclampsia. One hundred and twenty pregnant women were enrolled in this study and divided into three groups of 40 each-Control group, HR group (women at high risk of preeclampsia) and PET group (Preeclampsia group). Serum trace element levels were estimated by inductively coupled plasma optical emission spectrophotometer. The analysis found that mean values of Ca, Mg and Zn were 90.08 ± 6.38, 19.33 ± 3.32 and 1.30 ± 0.83 mg/L respectively in normotensive control and 77.85 ± 4.47, 15.44 ± 1.43 and 0.98 ± 0.63 mg/L respectively in the HR group. The mean values of Ca, Mg and Zn in the preeclamptic group were 70.37 ± 4.66, 13.58 ± 1.98 and 0.67 ± 0.59 mg/L, respectively. Interelement analysis reflected a negative correlation between Ca and Mg and between Mg and Zn whereas positive correlation between Ca and Zn in preeclamptic women. However the correlation was not statistically significant. In conclusion, our study suggests that decreased levels of these trace elements in serum may act as predisposing factors in pathogenesis of Preeclampsia.