Effect of inducible nitric oxide synthase on apoptosis in Candida-induced acute lung injury

Abstract

Excessive nitric oxide (NO) generated by inducible nitric oxide synthase (iNOS) aggravates acute lung injury (ALI) by producing peroxinitrite. We previously showed that the expression of iNOS and lung injury were suppressed by inhalation of a novel iNOS inhibitor, ONO-1714, in mice with Candida-induced ALI, and that nitric oxide produced by iNOS and apoptosis of epithelial cells were found to have a crucial role in Candida-induced ALI. In the present study, we investigated the effect of NO on the apoptosis of alveolar epithelial cells in Candida-induced ALI. Mice were pretreated by inhalation of ONO-1714 or saline (vehicle control of ONO-1714), and were given an intravenous injection of Candida albicans to induce ALI. After 24 h from injection of Candida albicans, we performed bronchoalveolar lavage and removed lung tissues. We assessed apoptosis on the basis of TUNEL staining and caspase 3 activity. Our results showed that apoptosis was suppressed by inhibition of iNOS-derived NO production by ONO-1714 inhalation. The augmented production of NO increased FasL, TNF-α, and mRNA production of Bax of lung that induced apoptosis of alveolar epithelial cells. Inhibition of iNOS-derived NO production by ONO-1714 inhalation ameliorated Candida-induced ALI and improved survival by suppressing apoptosis of alveolar epithelial cells.

Nanotechnology for delivery of peptide nucleic acids (PNAs)

“…Increased expression of iNOS in macrophages produces nitric oxide (NO), which results in tissue damage [120, 121]. Inhibition of iNOS reduces the accumulation of NO leading to improved outcome from ALI in experimental models[122]. An iNOS imaging probe was prepared by electrostatic complexation between a radiolabelled antisense PNA-YR 9. .…”

Candida albicans interactions with epithelial cells and mucosal immunity

“…Since the C. albicans hyphal cell wall is highly glycosylated this may provide an important mechanism for the induction of apoptosis in vivo , as it can be envisaged that once C. albicans hyphae are endocytosed into the EC the glycan moieties might then induce cell cycle arrest and activate apoptotic mechanisms to promote survival and potentially pathogenicity. Irrespective of the fungal moieties that activate apoptosis, once triggered, the production of nitric oxide (via peroxynitrite) by ECs may enhance C. albicans -induced mucosal injury [68]. …”

Hyperglycemia induces inducible nitric oxide synthase gene expression and consequent nitrosative stress via c-Jun N-terminal kinase activation

“…nNOS and eNOS are constitutively expressed at low levels. When iNOS is induced, it generates very high concentrations of NO 16. NO has been shown to be involved in cell differentiation, proliferation and apoptosis 17–19.…”