Splenic B lymphocyte programmed cell death is prevented by nitric oxide release through mechanisms involving sustained Bcl-2 levels.

Genaro, Ana Marı́a; Hortelano, Sonsoles; Álvarez, Alberto; Martı́nez, Carmen; Boscá, Lisardo

doi:10.1172/jci117869

Cited by 318 publications

(158 citation statements)

References 45 publications

(49 reference statements)

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“…Although studies have shown that NO or related molecules can exert either pro-or anti-apoptotic effects depending on the cell type and stimulus (39,(43)(44)(45)(46)(47)(48)(49), the emerging picture is one where the predominant physiologic effect of NOS is inhibition of apoptosis. For instance, NO inhibits apoptosis in murine splenic B cells, human B cell lines, rat ovarian follicles, and human eosinophils (39,(47)(48)(49). The cellular factors and target proteins that are responsible for the specificity of NO-related effects on apoptosis remain to be determined.…”

Section: Discussionmentioning

confidence: 99%

Nitric Oxide Inhibits Fas-induced Apoptosis

Mannick¹,

Miao²,

Stamler³

1997

Journal of Biological Chemistry

297

168

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Section: Discussionmentioning

confidence: 99%

Nitric Oxide Inhibits Fas-induced Apoptosis

Mannick¹,

Miao²,

Stamler³

1997

Journal of Biological Chemistry

297

168

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“…In splenic B cells, NO induces Bcl-2 expression and prevent apoptosis (Genaro et al, 1995). Thus, different types of cells appear to differ in the regulation of Bcl-2 expression.…”

Section: Discussionmentioning

confidence: 99%

Growth factors prevent changes in Bcl-2 and Bax expression and neuronal apoptosis induced by nitric oxide

et al. 1998

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Recent studies have shown that nitric oxide (NO) donors can trigger apoptosis of neurons, and growth factors such as insulin-like growth factor-1 (IGF-1) and basic fibroblast growth factor (bFGF) can protect against NO-induced neuronal cell death. The purpose of this study was to elucidate the possible mechanisms of NO-mediated neuronal apoptosis and the neuroprotective action of these growth factors. Both IGF-1 and bFGF prevented apoptosis induced by NO donors, sodium nitroprusside (SNP) or 3-morpholinosydnonimin (SIN-1) in hippocampal neuronal cultures. Incubation of neurons with SNP induced caspase-3-like activation following downregulation of Bcl-2 and upregulation of Bax protein levels in cultured neurons. Treatment of neurons with a bax antisense oligonucleotide inhibited the caspase-3-like activation and neuronal death induced by SNP. In addition, treatment of neurons with an inhibitor of caspase-3, Ac-DEVD-CHO, together with SNP did not affect the changes in the protein levels, although it inhibited NO-induced cell death. Pretreatment of cultures with either IGF-1 or bFGF prior to NO exposure inhibited caspase-3-like activation together with the changes in Bcl-2 and Bax protein levels. These results suggest that the changes in Bcl-2 and Bax protein levels followed by caspase-3-like activation are a component in the cascade of NOinduced neuronal apoptosis, and that the neuroprotective actions of IGF-1 and bFGF might be due to inhibition of the changes in the protein levels of the Bcl-2 family.

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“…They also discovered that treatment of H460 cells with the stress inducers Fas ligand or buthionine sulfoxide also induced Bcl-2 S-nitrosylation. Several observations clearly demonstrate that nitric oxide from iNOS involving Bcl-2 is important in preventing normal B-cell lymphocyte apoptosis 143 , as in human B-cell lymphomas [144][145][146] . In the case of the treatment of B-cell lymphomas with resveratrol, it was shown to prevent iNOS expression, to cause decreased expression levels of Bcl-2, and to enhance cellular apoptosis 145,146 .…”

Section: Bcl-2 S-nitrosylation and Cancer Cell Apoptosismentioning

confidence: 99%

Nitric Oxide and Cancer Development

et al. 2007

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Abstract:The role of nitric oxide (NO) in cancer development has become a very active research area. This review presents an overview of many studies that implicate an important role of NO in the development of cancer. These include results in experimental models as well as many observations made on NO and inducible nitric oxide synthase (iNOS) in human cancers. Our survey of the literature has allowed us to conclude that in general large levels of NO will kill cancer cells but paradoxically at intermediate to lower levels NO prevents cancer cell apoptosis and enhances tumor growth. This basic tenet has been demonstrated in many experimental models. The mechanistic basis of how intermediate levels of NO mediate tumor development is an active area of research and is the subject of this review. NO mediated S-nitrosylation of key enzymes and regulatory proteins plays a critical role. Key proteins S-nitrosylated which enhance tumor development include several caspases involved in apoptosis, PTEN the tumor suppressor protein, Bcl-2 the mitochondrial protein which protects from apoptosis, OGG1 the DNA repair protein and methionine adenosyl transferase the liver protein which synthesizes adenosylmethionine. The S-nitrosylation of these proteins enhances DNA mutations, prevents cancer cell apoptosis and enhances oncogenic cell growth. (J Toxicol Pathol 2007; 20: 77-92)

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Splenic B lymphocyte programmed cell death is prevented by nitric oxide release through mechanisms involving sustained Bcl-2 levels.

Cited by 318 publications

References 45 publications

Nitric Oxide Inhibits Fas-induced Apoptosis

Nitric Oxide Inhibits Fas-induced Apoptosis

Growth factors prevent changes in Bcl-2 and Bax expression and neuronal apoptosis induced by nitric oxide

Nitric Oxide and Cancer Development

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