Nitric oxide-modulated marker gene expression of signal transduction pathways in lung endothelial cells.

Nitric oxide (NO) is a signal molecule involved in regulation of physiological and pathophysiological functions of the vascular endothelium such as apoptosis. We examined whether NO-modulates marker gene expression of signal transduction pathways in cultured pulmonary artery endothelial cell (PAEC). Cells were exposed to a NO donor, 1 mM NOC-18, for 0.5, 5, and 24 h, thereafter, expression levels of 96 marker genes associated with 18 signal transduction pathways were assessed using a signal transduction pathway-finder microarray analysis system. NO modulation of apoptotic pathways and nuclear factor (NF) microarray were further analyzed. Gene array analyses revealed that 17 genes in 13 signal pathways were up- or down-regulated in cells exposed to NO, four of which were significantly altered by NO and are associated with apoptotic pathways. Apoptotic pathways resulted in identification of 11 genes in this group. Nuclear factor microarray studies demonstrated that NO-modulated expression of these signal transduction genes was associated with regulation of NF-binding activities. Gel shift analysis verified the effects of NO on DNA-binding activity of NF. These results demonstrated that NO signaling modulates at least 13 signal transduction pathways including apoptosis-related families in PAEC.