The Effect of Various Nitric Oxide-Donor Agents on Hydrogen Peroxide-Mediated Toxicity: A Direct Correlation between Nitric Oxide Formation and Protection

Wink, David A.; Cook, John A.; Pacelli, Roberto; DeGraff, William; Gamson, Janet; Liebmann, James; Krishna, Murali C.; Mitchell, James B.

doi:10.1006/abbi.1996.0304

Cited by 203 publications

(121 citation statements)

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“…Similarly, another NO donor, glycerol trinitrate (GTN) induced Apo2L/TRAIL mRNA in human leukemia cells and demonstrated antitumor activity (55). However, most conventional NO donors, especially those with short half-lives such as GTN, SNP, and SNAP, induce significant toxicity to normal cells due to spontaneous NO release (56,57), a drawback to their use.…”

Section: Discussionmentioning

confidence: 99%

Suppression of NF-κB Survival Signaling by Nitrosylcobalamin Sensitizes Neoplasms to the Anti-tumor Effects of Apo2L/TRAIL

Chawla‐Sarkar

Bauer

Lupica

et al. 2003

Journal of Biological Chemistry

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We have previously demonstrated the anti-tumor activity of nitrosylcobalamin (NO-Cbl), an analog of vitamin B12 that delivers nitric oxide (NO) and increases the expression of tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) and its receptors in human tumors. The specific aim of this study was to examine whether NO-Cbl could sensitize drug-resistant melanomas to Apo2L/TRAIL. Antiproliferative effects of NO-Cbl and Apo2L/TRAIL were assessed in malignant melanomas and non-tumorigenic melanocyte and fibroblast cell lines. Athymic nude mice bearing human melanoma A375 xenografts were treated with NO-Cbl and Apo2L/TRAIL. Apoptosis was measured by TUNEL and confirmed by examining levels and activity of key mediators of apoptosis.

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Section: Discussionmentioning

confidence: 99%

Suppression of NF-κB Survival Signaling by Nitrosylcobalamin Sensitizes Neoplasms to the Anti-tumor Effects of Apo2L/TRAIL

Chawla‐Sarkar

Bauer

Lupica

et al. 2003

Journal of Biological Chemistry

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“…Although it has been proposed that NO causes cell death (9,10), the above data show that compounds that only release NO, such as NOC-5 and NOC-12, at concentrations as high as 2 mM did not cause chondrocyte cell death in either the monolayer or alginate bead culture systems. As shown in other cell types (30)(31)(32), these NONOate compounds also had the capacity to afford protection against oxidative stress induced by both L-cystine and GSH depletion and by the addition of an oxidant (H 2 O 2 or tBH). It is plausible that in OA cartilage, pathologically high levels of NO coupled to increased intracellular O 2 Ϫ production do exist (19,20).…”

Section: Discussionmentioning

confidence: 73%

“…It has been reported that NO has the capacity to be cytoprotective under conditions of oxidative stress (14,(30)(31)(32); therefore, the protective capacity of NOC-5, NOC-12, SIN-1, and SNP was assessed under conditions of oxidative stress caused by 50 M tBH. To address the assumption that intracellular thiols might have an antioxidant effect on the survival of chondrocytes, cells were cultured in RPMI 1640 in the absence and presence of L-cystine and GSH for 24 hours prior to incubation with the oxidant and the respective NO donor compound.…”

Section: No and Chondrocyte Survival 397mentioning

confidence: 99%

Nitric oxide–mediated chondrocyte cell death requires the generation of additional reactive oxygen species

Carlo

Loeser

2002

Arthritis & Rheumatism

227

178

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Objective. Chondrocyte cell death, possibly related to increased production of endogenous nitric oxide (NO), has been observed during the pathogenesis of osteoarthritis and rheumatoid arthritis. The purpose of this study was to investigate the potential role of NO in causing chondrocyte cell death and to determine the contribution of other reactive oxygen species (ROS).Methods. Cell death and cytotoxicity were evaluated in human articular chondrocytes in response to various NO donor compounds with and without agents that stimulate or inhibit the production of additional ROS using both the alginate bead and the monolayer culture systems. Cell death was quantified by a total cell count with fluorescent labels, and cytotoxicity was measured as a function of cellular NADH-and NADPHdependent dehydrogenase activity. To determine if the redox status of the chondrocyte could influence the observed effect of NO, cells were preincubated for 24 hours in L-cystine-and glutathione (GSH)-depleted media to reduce intracellular GSH levels, a major defense mechanism against oxidative stress. Apoptosis was analyzed with the quantification of histoneassociated DNA fragments. Conclusion. These results show that NO by itself is not cytotoxic to cultured chondrocytes and can even be protective under certain conditions of oxidative stress. Chondrocyte cell death from NO occurs under conditions where other ROS are also generated. Results. Treatment of chondrocytes with peroxynitrite (ONOONitric oxide (NO) participates in the normal functioning of a wide array of mammalian processes, including vasodilation, inhibition of platelet aggregation, neurotransmission, and macrophage-mediated immunity (1-4). Paradoxically, however, NO has also been proposed to be the cytotoxic species responsible for an increasing number of pathologic disorders, including rheumatic (5) and neurodegenerative (6) diseases. Expression of inducible nitric oxide synthase (iNOS) has been associated with chondrocytes during the pathogenesis of osteoarthritis (OA) (7) and rheumatoid arthritis (RA) (8); however, the exact role of NO in this regard is not fully understood. While it has been reported that NO causes chondrocyte cell death (9,10), other more recent reports have proposed NO to be a physiologic regulator of mitochondrial respiration in chondrocytes (11,12). Moreover, production of high levels of endogenous NO by overexpression of the iNOS gene in transfected chondrocytes did not cause cell death (13).The direct investigation of the function of exogenous NO production on chondrocytes has been hampered by the lack of uniformity that exists between the different types of NO donor compounds. Knowledge of the precise reactive nitrogen species (RNS) that is

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“…NO, an activator of soluble guanylate cyclase, has previously been shown to cause an increase in the cellular [cGMP] in parotid acinar cells [11,12]. We found that stimulation of rat parotid acinar cells with 200 µM SNAP, a well-characterized NO donor that releases NO spontaneously within seconds of being dissolved [13], induces a strong sustained rise in the [cGMP] corresponding to an increase of 900 % after 10 s [11]. To investigate whether this rise in [cGMP] is associated with a change in [Ca# + ] i , we measured [Ca# + ] i in individual fura 2-loaded cells from rat parotid acini.…”

Section: The No-induced Rise In [Ca 2 + ] I Is Cgmp-mediatedmentioning

confidence: 81%

Nitric oxide and cGMP activate Ca2+-release processes in rat parotid acinar cells

et al. 2001

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We characterized the enzymic properties of ADP-ribosyl cyclase in rat parotid acinar cells by using a fluorescence technique. ADP-ribosyl cyclase is capable of synthesizing the Ca# + -mobilizing nucleotide cADP-ribose (cADPR) from NAD + and has previously been shown to be regulated by cGMP via a cGMP-dependent protein kinase (G kinase). We therefore investigated whether NO\cGMP-activated pathways are present in rat parotid acinar cells and whether NO\cGMP signalling exerts control over cellular Ca# + signalling processes. Our results showed that stimulation of acinar cells with adrenaline, isoproterenol, substance P and NO resulted in a rise in the [cGMP]. In addition, NO induced a release of Ca# + from intracellular ryanodine-

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The Effect of Various Nitric Oxide-Donor Agents on Hydrogen Peroxide-Mediated Toxicity: A Direct Correlation between Nitric Oxide Formation and Protection

Cited by 203 publications

References 0 publications

Suppression of NF-κB Survival Signaling by Nitrosylcobalamin Sensitizes Neoplasms to the Anti-tumor Effects of Apo2L/TRAIL

Suppression of NF-κB Survival Signaling by Nitrosylcobalamin Sensitizes Neoplasms to the Anti-tumor Effects of Apo2L/TRAIL

Nitric oxide–mediated chondrocyte cell death requires the generation of additional reactive oxygen species

Nitric oxide and cGMP activate Ca2+-release processes in rat parotid acinar cells

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