Gene interactions and pathways from curated databases and text-mining
J Cell Biochem 2009, PMID: 19306295

Clinorotation upregulates inducible nitric oxide synthase by inhibiting AP-1 activation in human umbilical vein endothelial cells.

Wang, Yong-Chun; Zhang, Shu; Du, Ting-Yuan; Wang, Bing; Sun, Xi-Qing

Alterations of nitric oxide contribute to post-flight orthostatic intolerance. The aim of this study was to investigate the changes of inducible nitric oxide synthase (iNOS) and the mechanisms underlying regulation of iNOS by simulated microgravity in human umbilical vein endothelial cells (HUVECs). Clinorotation, a simulated-model of microgravity, increased iNOS expression and promoter activity in HUVECs. The transactivations of NF-kappaB and AP-1 were suppressed by 24 h clinorotation. A key role for AP-1, but not NF-kappaB in the regulation of iNOS was shown. (1) PDTC, a NF-kappaB inhibitor, had no effect on clinorotation upregulation of iNOS. (2) SP600125, a JNK-specific inhibitor, which resulted in inhibition of AP-1 activity, enhanced the iNOS expression and promoter activity in clinorotation. (3) Overexpression of AP-1 remarkably attenuated the upregulation effect of clinorotation. These findings indicate that clinorotation upregulates iNOS in HUVECs by a mechanism dependent on suppression of AP-1, but not NF-kappaB. These results support a key role for AP-1 in the signaling of postflight orthostatic intolerance.

Diseases/Pathways annotated by Medline MESH: Orthostatic Intolerance
Document information provided by NCBI PubMed

Text Mining Data

iNOS ⊣ AP-1: " A key role for AP-1 , but not NF-kappaB in the regulation of iNOS was shown "

NF-kappaB ⊣ AP-1: " These findings indicate that clinorotation upregulates iNOS in HUVECs by a mechanism dependent on suppression of AP-1 , but not NF-kappaB "

Manually curated Databases

No curated data.