In cultured endothelial cells, incubation with TNF-α (50 ng/ml) for 48 h markedly reduced viability of endothelial cells. A 6 h preincubation with Sper/NO (0.03- -1 μM) protected endothelial cells in a concentration-dependent manner and increased viability by 63% of control. The NO scavenger PTIO (30 μM) completely abolished cytoprotection by Sper/NO. A cytoprotective effect comparable to Sper/NO was observed when preincubating the cells with 8-bromo cyclic GMP (1-10 μM). Moreover, no protection by Sper/NO occurred in the presence of ODQ (0.1 μM), a selective inhibitor of soluble guanylyl cyclase. Our results demonstrate that NO produces a long-term endothelial protection against cellular injury by TNF-α, presumably via a cyclic GMP-dependent pathway.
Bibliographical noteFunding Information:
This work was supported by the Deutsche Forschungsgemeinschaft (Schr 298/8-1). We would like to thank Martina Heidler for assistance in the preparation of this manuscript.
- Cyclic GMP
- Endothelial cell
- Nitric oxide
- Tumor necrosis factor-α