A two-photon ratiometric probe for hydrogen polysulfide (H₂S_n): Increase in mitochondrial H₂S_n production in a Parkinson’s disease model

다국어 초록 (Multilingual Abstract)

<P><B>Abstract</B></P> <P>Hydrogen polysulfide (H<SUB>2</SUB>S<SUB>n</SUB>, n>1), which is primarily generated during the crosstalk between H<SUB>2</SUB>S and reactive species (ROS and RNS), is receiving increasing attention in biochemical research. H<SUB>2</SUB>S<SUB>n</SUB> 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 (<B>SPS-M1</B>) for in situ detection of H<SUB>2</SUB>S<SUB>n</SUB> and its application to a PD model to account the H<SUB>2</SUB>S<SUB>n</SUB> levels. The probe exhibited selective and fast response to H<SUB>2</SUB>S<SUB>n</SUB> along with a marked blue-to-green color change. <B>SPS-M1</B> is sensitive enough to quantitative detection of endogenous H<SUB>2</SUB>S<SUB>n</SUB> content in mitochondria using two-photon microscopy (TPM). Ratiometric TPM imaging of live neurons and brain slices using <B>SPS-M1</B> revealed that H<SUB>2</SUB>S<SUB>n</SUB> production is increased to a greater extent in the A53 T α-synuclein (α-syn) overexpressing model than in the wild-type control. These findings suggest that the interactions of H<SUB>2</SUB>S and the increased ROS caused by α-syn overexpression may generate more H<SUB>2</SUB>S<SUB>n</SUB>. By employing our recently published TP probe for mitochondrial H<SUB>2</SUB>S, we also found the relationship between the H<SUB>2</SUB>S<SUB>n</SUB> and H<SUB>2</SUB>S; increased H<SUB>2</SUB>S<SUB>n</SUB> and decreased H<SUB>2</SUB>S levels, indicating that H<SUB>2</SUB>S and H<SUB>2</SUB>S<SUB>n</SUB> may play a significant role in the pathogenesis of PD. This result may be useful to biomedical studies, including PD.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A two-photon excitable and emission ratiometric probe for hydrogen polysulfide (H<SUB>2</SUB>S<SUB>n</SUB>) in mitochondria was developed. </LI> <LI> The probe is able to direct visualization of the endogenous H<SUB>2</SUB>S<SUB>n</SUB> level using two-photon microscopy (TPM). </LI> <LI> Ratiometric TPM imaging revealed that H<SUB>2</SUB>S<SUB>n</SUB> production is increased in a Parkinson’s Disease model. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>