DPTA NONOate

DPTA NONOate is a diazeniumdiolate small molecule nitric oxide (NO) donor with a reported NO release half-life of 5 hr (22-25°C). NO release conferred by DPTA NONOate blocked cisplatin-induced cell death in lung carcinoma H-460 cells, suggesting that the expression of Bcl-2, a primary mediator of tumor resistance to cisplatin, is regulated by NO. This mechanism of Bcl-2 regulation was elucidated with DPTA NONOate and other NO donors/inhibitors and ultimately correlated to NO-induced S-nitrosylation of the Bcl-2 protein. This, in turn, blocks the ubiqutination and subsequent proteasomal degradation of the protein. DPTA NONOate release of NO is demonstrated to attenuate the pulmonary hypertension induced by group B Streptococcus exposure.