Observation of formaldehyde-induced ER stress by an ER-targeting two-photon probe

The presence of formaldehyde (FA) residue in leather during processing impacts the quality of the leather. Additionally, FA penetrates the nervous system through inhalation and skin contact, resulting in neuroinflammation and the build-up of misfolded proteins in the brain. Furthermore, it disrupts the endoplasmic reticulum, leading to abnormal protein aggregation and endoplasmic reticulum stress. As a result, the development of a dependable approach for monitoring endoplasmic reticulum stress caused by FA in scrap leather is crucial. With this research we developed a two-photon fluorescence probe (SKD-1-HCHO) sensitive to FA and targeting the endoplasmic reticulum. The extent of endoplasmic reticulum stress during the neuroinflammation process induced by scrap leather was investigated. According to the experimental results, the probe displayed a rapid Turn-ON response, remarkable specificity, and high sensitivity toward FA in the two-photon mode. Moreover, the probe exhibited an extensive linear range both in vitro and in cells. The induction of neuroinflammation by scrap leather was observed through BV-2 cells and mice. It was found that the formaldehyde content in scrap leather could induce cellular inflammatory responses, leading to initiation of endoplasmic reticulum stress processes. Significantly, while the anti-inflammatory drug NS-398 could not regulate the formaldehyde levels in cells, it could significantly inhibit cellular inflammation and the process of endoplasmic reticulum stress.