A two-photon ratiometric probe for hydrogen polysulfide (H2Sn): Increase in mitochondrial H2Sn production in a Parkinson's disease model

Hydrogen polysulfide (H2S, n > 1), which is primarily generated during the crosstalk between H2S and reactive species (ROS and RNS), is receiving increasing attention in biochemical research. H2S is mostly generated in the mitochondria, and abnormal mitochondrial function and oxidative stress are directly related to many disorders including Parkinson's disease (PD). We now report a two-photon fluorescent probe (SPS-M1) for in situ detection of H2S and its application to a PD model to account the H2S levels. The probe exhibited selective and fast response to H2S along with a marked blue-to-green color change. SPS-M1 is sensitive enough to quantitative detection of endogenous H2S content in mitochondria using two-photon microscopy (TPM). Ratiometric TPM imaging of live neurons and brain slices using SPS-M1 revealed that H2S production is increased to a greater extent in the A53 T a-synuclein (a-syn) overexpressing model than in the wild-type control. These findings suggest that the interactions of H2S and the increased ROS caused by alpha-syn overexpression may generate more H2S. By employing our recently published TP probe for mitochondrial H2S, we also found the relationship between the H2S and H2S; increased H2S and decreased H2S levels, indicating that H2S and H2S may play a significant role in the pathogenesis of PD. This result may be useful to biomedical studies, including PD.