title: Sulphide signalling potentiates apoptosis through the up-regulation of IP3 receptor types 1 and 2.
abstract: OBJECTIVE
  To investigate an interaction between the calcium and sulphide signalling pathways, particularly effects of the slow H2 S release donor morpholin-4-ium-4-methoxyphenyl-(morpholino)-phosphinodithioate (GYY4137) on the expression of inositol 1,4,5-trisphosphate receptors (IP3 R) with the possible impact on the apoptosis induction in HeLa cells.
  
  
  METHODS
  Gene expression, Western blot analysis, apoptosis determination by Annexin-V-FLUOS and drop in mitochondrial membrane potential by 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide (JC1) and immunofluorescence were used to determine differences in control and GYY4137-treated HeLa cells.
  
  
  RESULTS
  In HeLa cell line, GYY4137 (10 μm) up-regulated expression of the IP3 R1 and IP3 R2, but not IP3 R3 on both mRNA and protein levels. Concurrently, cytosolic calcium increased and reticular calcium was depleted in concentration-dependent manner, partially by the involvement of IP3 R. Depletion of calcium from reticulum was accompanied by increase in endoplasmic reticulum (ER) stress markers, such as X-box, CHOP and ATF4, thus pointing to the development of ER stress due to GYY4137 treatment. Also, GYY4137 treatment of HeLa cells increased the number of apoptotic cells.
  
  
  CONCLUSIONS
  These results suggest an involvement of H2 S in both IP3 -induced calcium signalling and induction of apoptosis, possibly through the activation of ER stress.
authors.affiliation: Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Bratislava, Slovak Republic.
authors.forename: L
authors.initials: L
authors.lastname: Lencesova
authors.forename: S
authors.initials: S
authors.lastname: Hudecova
authors.forename: L
authors.initials: L
authors.lastname: Csaderova
authors.forename: J
authors.initials: J
authors.lastname: Markova
authors.forename: A
authors.initials: A
authors.lastname: Soltysova
authors.forename: M
authors.initials: M
authors.lastname: Pastorek
authors.forename: J
authors.initials: J
authors.lastname: Sedlak
authors.forename: M E
authors.initials: ME
authors.lastname: Wood
authors.forename: M
authors.initials: M
authors.lastname: Whiteman
authors.forename: K
authors.initials: K
authors.lastname: Ondrias
authors.forename: O
authors.initials: O
authors.lastname: Krizanova
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics / Q000378:metabolism*; D009025:Morpholines; D009946:Organothiophosphorus Compounds; D015854:Up-Regulation
chemical_list: C529376:GYY 4137; C506926:ITPR1 protein, human; C506927:ITPR2 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D009025:Morpholines; D009946:Organothiophosphorus Compounds; D006862:Hydrogen Sulfide
keywords: IP3 receptors; apoptosis; endoplasmic reticulum stress; sulphide signalling