title: Hydrogen sulfide regulates cardiac sarcoplasmic reticulum Ca(2+) uptake via K(ATP) channel and PI3K/Akt pathway.
abstract: OBJECTIVE
  To investigate the effects of hydrogen sulfide (H(2)S) on calcium uptake activity of the rat cardiac sarcoplasmic reticulum (SR) and possible signaling.
  
  
  METHODS
  Crude SR was isolated after treatment with H(2)S, then SR Ca(2+) uptake and SR Ca(2+)-ATPase (SERCA) activity was measured by the isotopic tracer method. The possible roles of the K(ATP) channel and PI3K/Akt and SR-membrane protein phospholamban (PLB) pathway were analyzed by specific blockers, and target protein activation was assayed by measuring protein phosphorylation.
  
  
  RESULTS
  Exogenous H(2)S lowered Ca(2+) uptake into the SR time or concentration dependently, which was associated with decreased SERCA activity. Inhibiting endogenous H(2)S production by DL-propargylglycine increased SR Ca(2+) uptake and SERCA activity. H(2)S inhibition of PLB phosphorylation was through SERCA activity and was reversed by two PI3K inhibitors, wortmannin and LY294002. Glibenclamide (a K(ATP) channel blocker) blocked the inhibitory effects of H(2)S on PLB and Akt phosphorylation. Pinacidil (a K(ATP) channel opener) reduced the phosphorylation of PLB and reversed the effects of DL-propargylglycine. H(2)S preconditioning increased PLB phosphorylation but did not affect SERCA activity.
  
  
  CONCLUSIONS
  Endogenous H(2)S transiently and reversibly inhibits SR Ca(2+) uptake in rat heart SR because of downregulated SERCA activity associated with PLB phosphorylation by the PI3K/Akt or K(ATP) channel. The transient negative regulation of SR Ca(2+) uptake and the L-type Ca(2+) channel contributes to Ca(2+) cycle homeostasis, which might be an important molecular mechanism in ischemic diseases.
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Science, Peking University, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Junbao
authors.initials: J
authors.lastname: Du
authors.forename: Guoheng
authors.initials: G
authors.lastname: Xu
authors.forename: Chaoshu
authors.initials: C
authors.lastname: Tang
authors.forename: Bin
authors.initials: B
authors.lastname: Geng
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D015221:Potassium Channels / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D000099211:Phospholamban
chemical_list: D002135:Calcium-Binding Proteins; D006862:Hydrogen Sulfide; D019869:Phosphatidylinositol 3-Kinases; D015221:Potassium Channels; D051057:Proto-Oncogene Proteins c-akt; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban; C117780:mitochondrial K(ATP) channel