Nitric oxide (NO): an effector of apoptosis

Abstract

It is appreciated that the production of nitric oxide (NO) from Larginine metabolism is an essential determinate of the innate immune system, important for nonspecific host defense, as well as tumor and pathogen killing. Cytotoxicity as a result of a substantial NO-formation is established to initiate apoptosis, characterized by upregulation of the tumor suppressor p53, changes in the expression of pro-and anti-apoptotic Bcl-2 family members, cytochrome c relocation, activation of caspases, chromatin condensation, and DNA fragmentation. Proof for the involvement of NO was demonstrated by blocking adverse effects by NO-synthase inhibition. However, NOtoxicity is not a constant value and NO may achieve cell protection as well. In part this is understood by transcription and translation of protective proteins, such as cyclooxygenase-2. Alternatively, protection may result as a consequence of a diffusion controlled NO/O 2 7 (superoxide) interaction that redirects the apoptotic initiating activity of NO towards protection. NO is endowed with the unique ability to initiate and to block apoptosis, depending on multiple variables that exist to be elucidated. The crosstalk between cell destructive and protective signaling pathways under the modulatory influence of NO will determine the impact of NO in apoptotic cell death and survival.

Resveratrol‐induced apoptosis in MCF‐7 human breast cancer cells involves a caspase‐independent mechanism with downregulation of Bcl‐2 and NF‐κB

“…67,68 Depending on cell type and intracellular redox status, NO can induce apoptosis or necrosis, acting as a molecular switch between the 2 processes. 61 RES increased NO production by MCF-7 cells, in particular at concentrations that also altered DC(m) and ROS generation and induced apoptosis.…”

Nitric oxide induces osteoblast apoptosis through the de novo synthesis of Bax protein

“…As a pathophysiological molecular effector, the chemical biology of NO can be divided into direct and indirect pathways. NO is a high energy radical and has the ability to cause DNA fragmentation by direct attack or indirect activation of serious signal transduction [3,37]. Previous studies have reported that NO induced by proinflammatory cytokines, tumor necrosis factor-ell, interleukin-1p and interferon-y, or an NO donor, Snitroso-N-acetyl-D,L-penicillamine would lead to DNA fragmentation and cell death of a mouse clonal osteogenic cell line, MC3T3-El cell [11,27].…”

On the Electronic Structure ofmer,trans‐[RuCl3(1H‐indazole)2(NO)], a Hypothetical Metabolite of the Antitumor Drug Candidate KP1019: An Experimental and DFT Study

“…[8,9] It should be also noted that NO, which is produced by a number of nitric oxide synthase (NOS) enzymes from larginine in the body, [10] plays a major role as a signaling molecule in biological signal transducing systems, for example, in blood pressure regulation, [11,12] neurotransmission, [13,14] inflammatory response, [15,16] as well as necrosis [17] and apoptosis. [18,19] Nitric oxide is therefore essential in biological systems, but both its excess as well as deficiency leads to pathologies.…”