Inducible Nitric Oxide Synthase and Apoptosis in Murine Proximal Tubule Epithelial Cells
Open Access
- 21 March 2006
- journal article
- research article
- Published by Oxford University Press (OUP) in Toxicological Sciences
- Vol. 91 (2), 493-500
- https://doi.org/10.1093/toxsci/kfj168
Abstract
Since inducible nitric oxide synthase (iNOS) and proximal tubule injury are known to be critical determinants of lipopolysaccharide (LPS)-induced renal failure, the role of nitric oxide (NO) in proximal tubule cell apoptosis was examined. An 18-h treatment with a combination of LPS (5 μg/ml) and interferon-γ (IFN-γ, 100 units/ml) synergistically induced iNOS and produced a 20-fold increase in NO generation in the TKPTS murine proximal tubule cell line. NO generation by LPS + IFN-γ was blocked by a specific iNOS blocker, L-N6-(1-iminoethyl)-lysine (L-NIL, 1mM). To assess the role of iNOS-derived NO in proximal tubule cell apoptosis, annexin V– and propidium iodide–labeled cells were analyzed by flow cytometry. Neither the induction of iNOS nor its inhibition produced significant apoptotic cell death in TKPTS cells. Two exogenous NO donors were used to examine the role of NO more directly in proximal tubule apoptosis. Although both sodium nitroprusside (SNP), an iron-containing, nitrosonium cation donor, and S-nitroso-N-acetylpenicillamine (SNAP), a noniron-containing, NO generator, produced a concentration-dependent increase in NO generation, only SNP increased apoptotic cell death in TKPTS cells (5.9 ± 0.7% in control cells vs. 21.6 ± 3.8% in SNP [500μM]-treated cells; n = 4–9; p < 0.01). SNP-mediated tubule cell apoptosis was not dependent on the activation of caspases or p53 but was possibly related to the generation of reactive oxygen species by SNP. Thus, in TKPTS cells induction of iNOS and generation of NO by LPS does not lead to tubular epithelial cell death.Keywords
This publication has 51 references indexed in Scilit:
- Disruption of renal peritubular blood flow in lipopolysaccharide-induced renal failure: role of nitric oxide and caspasesAmerican Journal of Physiology-Renal Physiology, 2005
- p53-dependent Caspase-2 Activation in Mitochondrial Release of Apoptosis-inducing Factor and Its Role in Renal Tubular Epithelial Cell InjuryOnline Journal of Public Health Informatics, 2005
- Mechanism of Bradykinin-Induced Ca2+Mobilization in Murine Proximal Tubule Epithelial CellsThe Journal of pharmacology and experimental therapeutics, 2005
- Oxidative stress-induced apoptosis in retinal photoreceptor cells is mediated by calpains and caspases and blocked by the oxygen radical scavenger CR-6Online Journal of Public Health Informatics, 2004
- Regulation of an inwardly rectifying K+channel by nitric oxide in cultured human proximal tubule cellsAmerican Journal of Physiology-Renal Physiology, 2004
- Differential Mechanisms of Nitric Oxide- and Peroxynitrite-Induced Cell DeathMolecular Pharmacology, 2004
- Regulation of the apoptosis–necrosis switchOncogene, 2004
- Human renal epithelial cells express iNOS in response to cytokines but not bacteriaKidney International, 2002
- Protective effect of deferoxamine on sodium nitroprusside-induced apoptosis in PC12 cellsNeuroscience Letters, 1998
- NF-κB and transcriptional control of renal epithelial-inducible nitric oxide synthaseKidney International, 1995