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Miro2 sulfhydration by CBS/H2S promotes human trophoblast invasion and…

- - - - Insufficient CTB migration and invasion into the maternal myometrium delay the transformation of CTB into the spiral artery endothelium
        
        thus leads to pregnancy related complications like Intra-uterus Growth Restriction (IUGR), pre-eclampsia (PE) and abortion as consequences
  - - - H2S in serum from PE patients was reported to be significantly decreased
        
        placenta samples from PE patients demonstrated shallow CTB migration and invasion [7] into the maternal myometrium
    - - cystathionine γ-lyase (CSE)
        
        which mainly functions in the cardiovascular system
        
        low concentration of H2S (less than 5 µM) stimulated CBS aggregation in trophoblasts indicating low H2S maintains CBS protein level as well as tissue H2S production.
      - cystathionine β-synthetase (CBS)
        
        in the central nervous system
      - 3-mercaptopyruvate sulfurtransferase (MST3)
        
        in mitochondria in mammals
  - - - CSE/CBS-H2S signal determines cell fates based on cell type and stress state
- - - - significant decrease (~50% reduction) of plasma H2S from PE patients comparing with that from normal pregnancy women
        
        CBS, CSE, and MST3 were all detected in human placenta
        
        assessed the distribution of CBS, CSE and MST3 in placenta.
        
        immunofluorescence results showed CBS and CSE were co-localized with CK-7 marked cells (extravillous invasive trophoblast, EVT marker) in placenta
    - - low dose of exogenous H2S donor application (GYY4137, 1 and 5 µM)
        
        evaluated the transcriptional expression of the gene CBS
        
        tested LONP1 expression in HTR-8/SVneo
        
        heat shock protein 60 (HSP60) was tested and increased significantly after GYY4137 application
        
        assessed the CBS distribution in the cellular compartment to find out if CBS localized differently in the cell.
  - - - transmission electron microscope (TEM) study
        
        mitochondria length/width ratio and length
        
        To study the functional significance of CBS-translocation onto mitochondria
        
        ATP and ROS production, Δψm
        
        designed and selected the most efficient si-CBS to knockdown the CBS translation
  - - - Live cell tracking was used to assess HTR-8/SVneo migration accumulative moving distance and speed under a confocal microscope
        
        The HTR-8/SVneo moving distance was recorded and analyzed for about 16 hours. The cell moving path was dotted with Harmony 4.9 software
        
        Mitochondrial division inhibitor 1 (Mdivi-1)