Overlooked role of aqueous chromate (VI) as a photosensitizer in enhancing the photochemical reactivity of ferrihydrite and production of hydroxyl radical.

The reactive oxygen species (ROS) photochemically generated from natural iron minerals have gained significant attention. Amidst the previous studies on the impact of heavy metal ions on ROS generation, our study addresses the role of the anion Cr(VI), with its intrinsic photoactivity, in influencing ROS photochemical generation with the co-presence of minerals. We investigated the transformation of inorganic/organic pollutants (Cr(VI) and benzoic acid) at the ferrihydrite interface, considering sunlight-mediated conversion processes (300-1000 nm). Increased photochemical reactivity of ferrihydrite was observed in the presence of aqueous Cr(VI), acting as a photosensitizer. Meanwhile, a positive correlation between hydroxyl radical (•OH) production and concentrations of aqueous Cr(VI) was observed, with a 650% increase of •OH generation at 50 mg L-1 Cr(VI) compared to systems without Cr(VI). Our photochemical batch experiments elucidated three potential pathways for •OH photochemical production under varying wet chemistry conditions: (1) ferrihydrite hole-mediated pathway, (2) chromium intermediate O-I-mediated pathway, and (3) chromium intermediates CrIV/V-mediated pathway. Notably, even in the visible region (> 425 nm), the promotion of aqueous Cr(VI) on •OH accumulation was observed in the presence of ferrihydrite and TiO2 suspensions, attributed to Cr(VI) photosensitization at the mineral interface. This study sheds light on the overlooked role of aqueous Cr(VI) in the photochemical reactivity of minerals, thereby enhancing our understanding of pollutant fate in acid mining-impacted environments.

Differences in endoplasmic reticulum stress signalling kinetics determine cell survival outcome through activation of MKP-1.

Endoplasmic reticulum (ER) stress signalling pathways are involved in various alterations of the central nervous system such as neurodegenerative diseases or ischemia. The current mechanisms linking ER stress activation to neuronal cell fate upon chronic or acute stresses remain however to be fully understood. Recent studies have associated ER stress severity and the relative activation levels of certain output pathways to influence cell-fate decisions. In the present report, to further test the impact of ER stress severity on neuronal survival, we designed an experimental system recapitulating acute and chronic stress in cerebellar granule neurons (CGNs) and c17.2 mouse neural stem cells (NSCs). Two well characterized ER stress inducers, tunicamycin (TM) and dithiothreitol (DTT), were used to induce "slow motion" and "fast motion" stresses, respectively. We show that the duration of JNK activation is critical for cell survival upon ER stress. TM-induced transient JNK activation is a protective event in CGNs and c17.2 NSCs via the phosphorylation of BAD, while DTT-induced prolonged JNK activation mediates pro-apoptotic signalling. In addition, we demonstrate that ER stress mediated MKP-1/DUSP1 expression regulates JNK activation kinetics. MKP-1 phosphorylation and protein expression level are differentially altered upon TM and DTT treatment. Increased MKP-1 protein stability via its phosphorylation on ser359 induced by TM accounts for transient JNK activation and the resulting cell survival in CGNs and c17.2 NSCs subjected to ER stress. These results suggest that MKP-1 plays a pivotal role in ER stress-induced cell apoptosis through regulating JNK-BAD signalling.

GABAB receptor activation protects neurons from apoptosis via IGF-1 receptor transactivation.

The G-protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs) play key roles in cell-cell communication. Several studies revealed important synergisms between these two types of receptors, with some of the actions of either receptor being mediated through transactivation of the other. Among the large GPCR family, GABA(B) receptor is activated by the neurotransmitter GABA, and is expressed in most neurons where it mediates slow and prolonged inhibition of synaptic transmission. Here we show that this receptor is involved in the regulation of life and death decisions of cerebellar granule neurons (CGNs). We show that specific activation of GABA(B) receptor can protect neurons from apoptosis through a mechanism that involves transactivation of the IGF-1 receptor (IGF-1R). Further work demonstrated that this cross talk was dependent on G(i/o)-protein, PLC, cytosolic Ca(2+), and FAK1 but independent of PKC, while IGF-1R-induced signaling involved Src kinase, PI3 kinase, and Akt activation. These results reveal a new function for this important GPCR and further highlight the importance of functional cross-talk networks between GPCRs and RTKs. Our results reveal GABA(B) receptor as a potential drug target for the treatment of neurodegenerative disorders.