Assessing the double-edged of extracellular signal-regulated kinase/CCAAT-enhancer-binding protein beta signaling pathway in arsenic-induced skin damage and its potential foodborne interventions.

Arsenic exposure is a major environmental public health challenge worldwide. As typical manifestations for arsenic exposure, the pathogenesis of arsenic-induced skin lesions has not been fully elucidated, as well as the lack of effective control measures. In this study, we first determined the short-term and high-dose arsenic exposure can increase the apoptosis rates, while long-term low-dose arsenic exposure decrease the apoptosis rates. Then, the HaCaT cells with knockdown and overexpression of CCAAT-enhancer-binding protein ß (CEBPB) and extracellular signal-regulated kinase (ERK) were constructed. The results demonstrate that knockdown of CEBPB and ERK can reduce NaAsO2 -induced cell apoptosis by inhibiting ERK/CEBPB signaling pathway and vice versa. Further cells were treated with Kaji-Ichigoside F1 (KF1). The results clearly show that KF1 can decrease the arsenic-induced cell apoptosis rates and the expression of ERK/CEBPB signaling pathway-related genes. These results provide evidence that ERK/CEBPB signaling pathway acts as a double-edged sword in arsenic-induced skin damage. Another interesting finding was that KF1 can alleviate arsenic-induced skin cell apoptosis by inhibiting the ERK/CEBPB signaling pathway. This study will contribute to a deeper understanding of the mechanisms of arsenic-induced skin cell apoptosis, and our findings will help to identify a potential food-borne intervention in arsenic detoxification.

Ferroptosis As a Mechanism for Health Effects of Essential Trace Elements and Potentially Toxic Trace Elements.

Ferroptosis is a unique form of programmed cell death driven by iron-dependent phospholipid peroxidation that was proposed in recent years. It plays an important role in processes of various trace element-related diseases and is regulated by redox homeostasis and various cellular metabolic pathways (iron, amino acids, lipids, sugars), as well as disease-related signaling pathways. Some limited pioneering studies have demonstrated ferroptosis as a mechanism for the health effects of essential trace elements and potentially toxic trace elements, with crosstalk among them. The aim of this review is to bring together research articles and identify key direct and indirect evidence regarding essential trace elements (iron, selenium, zinc, copper, chromium, manganese) and potentially toxic trace elements (arsenic, aluminum, mercury) and their possible roles in ferroptosis. Our review may help determine future research priorities and opportunities.