title: YC-1 prevents sodium nitroprusside-mediated apoptosis in vascular smooth muscle cells.
abstract: OBJECTIVE
  Nitric oxide signaling pathways are of central importance in both the maintenance of vascular homeostasis and the progression of vascular disease. Since smooth muscle cell apoptosis is associated with numerous vascular disorders, the authors investigated whether YC-1, a soluble guanylyl cyclase (sGC) activator, regulates apoptosis in vascular smooth muscle cells (VSMC).
  
  
  RESULTS
  Sodium nitroprusside (SNP) (1 mM) induced cGMP (guanosine 3':5'-cyclic monophosphate)-independent apoptosis in rat vascular smooth muscle cells using MTT assay and TUNEL-reaction techniques. Furthermore, sodium nitroprusside induced apoptosis via Bcl-2 down-regulation, cytochrome c release reaction, and caspase-3 activation by Western blotting analysis and enzymatic assay methods. YC-1 abolished these apoptotic signaling cascades and prevented apoptosis through a cGMP-involved pathway, and phosphatidylinositol (PI) 3-kinase behaved a downstream event in this pathway.
  
  
  CONCLUSIONS
  These results suggest that YC-1 inhibits sodium nitroprusside-induced vascular smooth muscle cells apoptosis via a cGMP- and phosphatidylinositol 3-kinase-involved inhibition on Bcl-2 down-regulation/cytochrome c release/caspase-3 activation cascades. The ability of YC-1 to prevent smooth muscle cell apoptosis may play an important role in blocking lesion formation at sites of vascular injury.
authors.affiliation: Pharmacological Institute, College of Medicine, National Taiwan University, No. 1, Jen-Ai Road, Section 1, 100 Taipei, Taiwan.
authors.forename: Shiow L
authors.initials: SL
authors.lastname: Pan
authors.forename: Jih H
authors.initials: JH
authors.lastname: Guh
authors.forename: Ya L
authors.initials: YL
authors.lastname: Chang
authors.forename: Sheng C
authors.initials: SC
authors.lastname: Kuo
authors.forename: Fang Y
authors.initials: FY
authors.lastname: Lee
authors.forename: Che M
authors.initials: CM
authors.lastname: Teng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D003864:Depression, Chemical; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D019254:Genes, bcl-2; D006162:Guanylate Cyclase / Q000378:metabolism*; D007191:Indazoles / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000032:analysis; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D007191:Indazoles; D017382:Reactive Oxygen Species; D014665:Vasodilator Agents; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; D009599:Nitroprusside; D045304:Cytochromes c; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A