Reverse transcription (RT -PCR analysis RT -PCRd significanalysisession of inducible nitrevealede significantNA and high lexpressionitric ofinduciblectionitricecoxideant parasynthaseected J774A.1 cells.
Considering that high levels of nitric oxide (NO) exert anti-cancer effect and the derivatives of oleanolic acid (OA) have shown potent anti-cancer activity, new O2-vinyl diazeniumdiolate-based NO releasing derivatives (5a l, 11a l) of OA were designed, synthesized, and biologically evaluated in the present study.
The most active compound 7 produced relatively high levels of nitric oxide (NO) and reactive oxygen species (ROS) in drug-resistant lung cancer A549/Taxol cells which over-express glutathione S-transferase π (GSTπ), and significantly inhibited the cells' proliferation (IC50 = 0.349 ± 0.051 μM), superior to the positive controls CDDO-Me, JS-K and Taxol.
In contrast, macrophages infected with subsp. tularensis (4A iv)) and LVS (4A ii)) expressed relatively high levels of nitric oxide and these strains exhibited minimal replication in these cells.
Based on an increasing body of information, it also seems that the generation of high levels of nitric oxide by iNOS during gut ischemia is involved in the pathogenesis of gut injury [16], [17], [32].
We have previously shown that ookinete invasion induces high levels of nitric oxide synthase expression in the cell cytoplasm [25] that is followed by peroxidase-mediated protein nitration [32] and proposed that these cellular responses limit Plasmodium survival [25] [32].
Since the F. tularensis strains that either replicated minimally or failed to replicate within rat BMDM (subsp. tularensis, LVS and subsp. novicida) also induced high levels of nitric oxide within the BMDM, we determined the effect that inhibition of nitric oxide production by the macrophages would have on F. tularensis replication.
Inducible nitric oxide synthase (iNOS) is responsible for generating high levels of nitric oxide (NO) in activated macrophages.
Inflammation caused by noninfective challengers may lead to inducible nitric oxide synthase synthesis and hence high levels of nitric oxide.
It can also be inhibited by high levels of nitric oxide (NO), which compete with O2 for the binding site.
