Disease relevance of DETA NONOate

• DETA-NONOate, a nitric oxide (NO) donor, induced cytostasis in the human breast cancer cells MDA-MB-231, and the cells were arrested in the G(1) phase of the cell cycle [1].
• However, NOC-18-induced hyperalgesia was not influenced by L-NAME [2].
• Upregulation of neurogenesis and reduction in functional deficits following administration of DEtA/NONOate, a nitric oxide donor, after traumatic brain injury in rats [3].
• However, L-NAME prolonged EMDv during anoxia and delayed EMDv recovery during reoxygenation while 100 microM DETA-NONOate had the opposite effects [4].
• Endothelium-independent vasodilation to deta-NONOate and pinacidil was not affected in acute and chronic hyperhomocysteinemia, demonstrating intact vascular smooth muscle reactivity [5].

High impact information on DETA NONOate

• We conclude that down-regulation of cyclin D1 protein by DETA-NONOate played an important role in the cytostasis and arrest of these tumor cells in the G(1) phase of the cell cycle [1].
• Synchronized population of the cells exposed to DETA-NONOate remained arrested at the G(1) phase of the cell cycle whereas untreated control cells progressed through the cell cycle after serum stimulation [1].
• Depolarization of mitochondrial membrane potential (MMP) occurred at 4 h of DETA-NONOate treatment, which returned to control values and which was followed by another wave of depolarization at 24 h [6].
• We used the long-acting NO donor DETA-NONOate, which, at a concentration of 1 mM, releases NO in the range produced by activated macrophages [6].
• Except to the HaCat cell line, all of the other human epithelioid cells were sensitive to the antiproliferation effect of S-nitroso-N-acetyl-penicillamine or Deta NONOate, whereas tumor cells had low if any response to sodium nitroprusside [7].

Chemical compound and disease context of DETA NONOate

• Acceleration of the development of thermal hyperalgesia induced by 1 and 10 microg NOC-18 was completely inhibited by Hb, but was not affected by either MK-801, L-NAME or MB [8].
• METHODS: Primary cultured fibroblasts derived from eosinophilic nasal polyps were exposed to NO donors (500 microM of S-nitroso-N-acetyl-D,L-penicillamine (SNAP) 1000 micoM of 3,3-bis(aminoethyl)-1-hydroxy-2-oxo-1-triazene (DETA-NONOate)) and various other compounds over a 24-hour incubation period [9].

Biological context of DETA NONOate

• FTI (25 microM) potentiated the action of lower concentrations of DETA-NONOate (25-100 microM) by inducing apoptosis in these cells within 24 h by increasing cytochrome c release and caspase-9 and -3 activation [10].
• The NO-releasing agent Deta-NONOate (ethanamine-2,2'-(hydroxynitrosohydrazone)bis-) had no effect on a chloramphenicol acetyltransferase (CAT) reporter gene under control of the fos promoter in BHK cells transfected with an empty vector or in cells transfected with a G-kinase Ibeta expression vector [11].
• The demonstration that pretreatment of glomeruli with the tyrosine kinase inhibitor, genistein, could largely prevent the effect of SNAP and DETA-NONOate confirmed the crucial role of tyrosine phosphorylation in the NO-induced increase of P(a) [12].
• DETA-NONOate, a nitric oxide donor, decreased day 4 blastocyst cell number and oxygen consumption, consistent with a role for nitric oxide in the inhibition mitochondrial cytochrome c oxidase [13].
• A specific K(Ca) channel inhibitor, iberiotoxin, decreased deta nonoate-induced vasodilation but to a lesser extent than ODQ [14].

Anatomical context of DETA NONOate

• ODQ (10 mumol/L) attenuated deta nonoate- and nitroglycerin-mediated relaxation of contracted aortas [15].
• The 1-substituted diazen-1-ium-1, 2-diolate NOC-18 induced HIF-1 DNA-binding activity in normoxic bovine pulmonary artery endothelial cells and rat aortic smooth muscle cells in a time- and dose-dependent manner [16].
• ODQ (10 mumol/L) reduced deta nonoate-stimulated cGMP production in COS-7 cells overexpressing soluble guanylyl cyclase and in rat aortic vascular smooth muscle cells [15].
• Deta nonoate produced a concentration-dependent relaxation of precontracted coronary arteries [14].
• Finally, L-arginine (10 mM) and NOC-18 (0.3 mM) inhibited both basal and Fe/Asc (0.1 mM/0.2 mM)-stimulated lipid peroxidation in X. laevis oocytes [17].

Associations of DETA NONOate with other chemical compounds

• Here we have determined whether mitochondrial membrane protein thiols can be S-nitrosated on exposure to free NO from 3,3-bis(aminoethyl)-1-hydroxy-2-oxo-1-triazene (DETA-NONOate) by interaction with S-nitrosoglutathione or S-nitroso-N-acetylpenicillamine (SNAP) and by the NO derivative peroxynitrite [18].
• In BHK cells co-transfected with guanylate cyclase and G-kinase expression vectors, CAT activity was increased 5-fold in the absence of Deta-NONOate and 7-fold in the presence of Deta-NONOate [11].
• Addition of NO donors, 1 mM S-nitroso-N-acetyl-DL-penicillamine (SNAP) or 1 mM diethylenetriamine-NO adduct (NOC-18), to PC12 cells resulted in a steady-state level of 1-3 microM: NO, rapid and almost complete inhibition of cellular respiration (within 1 min), and a rapid decrease in mitochondrial membrane potential within the cells [19].
• Nitric oxide donors such as DETA-NONOate promote functional recovery after stroke [20].
• Both SNP- and DETA-NONOate-induced gene expression had faded after 24 h, despite continued elevation of cGMP in the medium [21].

Gene context of DETA NONOate

• The iNOS selective inhibitor L-NIL also suppressed TNF-alpha-induced osteoclast survival, whereas low concentrations of NO releaser NOC-18 were sufficient to promote osteoclast survival [22].
• However, the NO donor NOC-18 (500 microM) increased HO-1 expression twofold and HO activity 25-fold, whereas cytomix treatment increased HO activity eightfold [23].
• By means of a competitive nitric oxide synthase (NOS) inhibitor: L-nitro arginine methyl ester (L-NAME) and a slow NO releasing: diethyl-aminetriamine (DETA-NONOate), we demonstrated that NO system could be the intermediary in the ET-1 diminishing P4 production [24].
• Costimulation with interferon-gamma (IFN-gamma) reversed the NOC-18-mediated suppression of IL-1alpha protein concentration into an almost fivefold increase in RAW 264.7 cells [25].
• Conversely, after addition of the NO-generating compound NOC-18, IL-1beta and IL-1alpha concentrations in supernatants were dose-dependently reduced [25].

Analytical, diagnostic and therapeutic context of DETA NONOate

• Similarly, microinjection of NOC 18 (10 nmol/50 nL) reduced MAP in both strains, and the depressor response was also significantly greater in SHR than in WKY (-38+/-7 versus -22+/-3 mm Hg, respectively; n=8, P<.05) [26].
• The protection exerted by increased Nrf2 activity was overcome by adding the NO donor DETA-NONOate to the co-cultures or by inhibiting GSH synthesis and release from astrocytes [27].
• 2. Exposure to S-nitrosothiols, DETA-NONOate and NO itself inhibited ongoing DNA synthesis and S phase progression in a concentration-dependent manner, as measured by thymidine incorporation and flow cytometry [28].
• In the sham-surgery control groups, intrathecal injection of 10 or 100 microg of NOC-18 did not produce any change in withdrawal latencies [8].
• Northern blot analysis revealed that the level of mRNA for osteocalcin, one of the osteoblastic differentiation markers, was enhanced in the ROB cells, which was continuously treated by NOC-18 [29].

References