Enhancement of CREB(superscript Serine-133) Phosphorylation through Nitric Oxide-Mediated Signaling Induced by Bacterial Lipopolysaccharide in Vascular Smooth Muscle Cells from Rats

San-Nan Yang；Chin-Hwa Yang；Li-Tung Huang；Yu-Tsun Wu；Chih-Lu Wang

atherosclerosis ； differentiation ； smooth muscle cell ； CREB

The Chinese Journal of Physiology

45卷2期（2002 / 06 / 30）

69 - 74

英文

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 (CREB(superscript Ser-133)) in cultured vascular smooth muscle cells (VSMCs) from rats. Addition of LPS (1-10 μg/ml) for 48 hours increased not only the production NO, but also the phosphorylation of CREB(superscript Ser-133) The use of NOS inhibitor (100-500 μM L-NAME) blocked the magnitudes of both LPS-induced NO production and CREB(superscript Ser-133) phosphorylation. In addition, either a guanylyl cyclase (GC) inhibitor (30μM ODQ) or a cGMP-dependent protein kinase (PKG) inhibitor (20μM(Rp)-8-pCPT-cGMPs) significantly attenuated the magnitudes of LPS-induced CREB(superscript Ser-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 CREB(superscript Ser-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.

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