title: Enhancement of CREBSerine-133 phosphorylation through nitric oxide-mediated signaling induced by bacterial lipopolysaccharide in vascular smooth muscle cells from rats.
abstract: Nitric oxide (NO) induced by bacterial lipopolysaccharide (LPS) plays a critical role in various patho-physiological implications, such as atherosclerosis, vasculitis and septic shock. In addition, cAMP-responsive element binding protein (CREB), an important transcription factor for cell differentiation, has been shown to be involved in atherosclerogenesis in VSMCs. Here we investigated the possibility whether LPS-induced NO signaling led to phosphorylation of cAMP-responsive element binding protein on Serine-133 (CREBSer-133) in cultured vascular smooth muscle cells (VSMCs) from rats. Addition of LPS (1-10 microg/ml) for 48 hours increased not only the production NO, but also the phosphorylation of CREBSer-133. The use of NOS inhibitor (100-500 microM L-NAME) blocked the magnitudes of both LPS-induced NO production and CREBSer-133 phosphorylation. In addition, either a guanylyl cyclase (GC) inhibitor (30 microM ODQ) or a cGMP-dependent protein kinase (PKG) inhibitor (20 microM (Rp)-8-pCPT-cGMPs) significantly attenuated the magnitudes of LPS-induced CREBSer-133 phosphorylation, suggesting the involvement of NO-GC-PKG signaling. Thus, the present study suggests that NO-mediated signaling activated by bacterial LPS, at least in part, enhance CREBSer-133 phosphorylation in cultured VSMCs. The findings here may provide not only signaling pathway involved in VSMC differentiation during inflammatory response, but also new insight into possible therapeutic intervention.
authors.affiliation: Department of Pediatrics, Chang-Gung Children's Hospital at Kaohsiung, Chang-Gung University, Niao-Sung, Kaohsiung, Taiwan 833, ROC. y520729@ms65.hinet.net
authors.forename: San Nan
authors.initials: SN
authors.lastname: Yang
authors.forename: Chin-Hwa
authors.initials: CH
authors.lastname: Yang
authors.forename: Li-Tung
authors.initials: LT
authors.lastname: Huang
authors.forename: Yu-Tsun
authors.initials: YT
authors.lastname: Wu
authors.forename: Chih-Lu
authors.initials: CL
authors.lastname: Wang
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D012694:Serine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D006162:Guanylate Cyclase