title: Baicalein, isolated from Scutellaria baicalensis, protects against endothelin-1-induced pulmonary artery smooth muscle cell proliferation via inhibition of TRPC1 channel expression.
abstract: BACKGROUND
  We investigated the antiproliferative effects of baicalein, isolated from Scutellaria baicalensis (Huang-qin), on ET-1-mediated pulmonary artery smooth muscle cells (PASMCs) proliferation and the mechanisms underlying these effects.
  
  
  METHODS
  Intrapulmonary artery smooth muscle cells were isolated and cultured from female Sprague-Dawley rats and used during passages 3-6. The proliferation of PASMCs was quantified by cell counting and XTT assay. The protein expression of TRPC1 and PKCα were determined by western blotting. The cell cycle pattern was assayed by flow cytometry. The intracellular calcium concentrations ([Ca(2+)](i)) were measured using the fluorescent indicator fura-2-AM and flow cytometry.
  
  
  RESULTS
  Baicalein (0.3-3 μM) inhibited PASMCs proliferation, promoted cell cycle progression, enhanced [Ca(2+)](i) levels, increased capacitative Ca(2+) entry (CCE), upregulated the canonical transient receptor potential 1 (TRPC1) channel and membrane protein kinase Cα (PKCα) expression induced by ET-1 (0.1 μM). The PKC activator PMA (1 μM) reversed the inhibitory effects of baicalein on ET-1-induced upregulation of TRPC1 expression and S phase accumulation, while the PKC inhibitor chelerythrine (1 μM) potentiated baicalein-mediated G(2)/M phase arrest and TRPC1 channel inhibition.
  
  
  CONCLUSIONS
  Our findings suggest that baicalein protects against ET-1-induced PASMCs proliferation via modulation of the PKC-mediated TRPC channel.
authors.affiliation: Department of Pharmacology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Lin
authors.forename: Rong-Jyh
authors.initials: RJ
authors.lastname: Lin
authors.forename: Kuo-Pyng
authors.initials: KP
authors.lastname: Shen
authors.forename: Zen-Kong
authors.initials: ZK
authors.lastname: Dai
authors.forename: Ing-Jun
authors.initials: IJ
authors.lastname: Chen
authors.forename: Jiunn-Ren
authors.initials: JR
authors.lastname: Wu
authors.forename: Bin-Nan
authors.initials: BN
authors.lastname: Wu
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000502:physiology*; D005260:Female; D044950:Flavanones / Q000302:isolation & purification / Q000494:pharmacology*; D005434:Flow Cytometry; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051571:Protein Kinase C-alpha / Q000037:antagonists & inhibitors; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D031364:Scutellaria baicalensis / Q000737:chemistry*; D050052:TRPC Cation Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D019332:Endothelin-1; D044950:Flavanones; D050052:TRPC Cation Channels; C096351:transient receptor potential cation channel, subfamily C, member 1; C006680:baicalein; D051571:Protein Kinase C-alpha; D002118:Calcium