Nitric oxide can function as either a killer molecule or an antiapoptotic effector in cardiomyocytes

Stefanelli, Claudio; Pignatti, Carla; Tantini, Benedetta; Stanic, Ivana; Bonavita, Francesca; Muscari, Claudio; Guarnieri, Carlo; Clô, Carlo; Caldarera, Claudio Marcello

doi:10.1016/s0167-4889(99)00045-2

Cited by 47 publications

(25 citation statements)

References 43 publications

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“…NO can induce apoptosis in some tumor cells, and this cell death can be blocked by increasing cellular redox potential (31). NO-mediated cell death requires a high rate of NO generation rather than a large total amount of NO production.…”

Section: Discussionmentioning

confidence: 99%

Cellular Non-heme Iron Content Is a Determinant of Nitric Oxide-mediated Apoptosis, Necrosis, and Caspase Inhibition

Kim¹,

Chung²,

Simmons³

et al. 2000

Journal of Biological Chemistry

224

131

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In this report, we tested the hypothesis that cellular content of non-heme iron determined whether cytotoxic levels of nitric oxide (NO) resulted in apoptosis versus necrosis. The consequences of NO exposure on cell viability were tested in RAW264.7 cells (a cell type with low non-heme iron levels) and hepatocytes (cells with high non-heme iron content). Whereas micromolar concentrations of the NO donor S-nitroso-N-acetyl-DL-penicillamine induced apoptosis in RAW264.7 cells, millimolar concentrations were required to induce necrosis in hepatocytes. Caspase-3 activation and cytochrome c release were evident in RAW264.7 cells, but only cytochrome c release was detectable in hepatocytes following high dose S-nitroso-N-acetyl-DL-penicillamine exposure. Pretreating RAW264.7 cells with FeSO 4 increased intracellular non-heme iron to levels similar to those measured in hepatocytes and delayed NO-induced cell death, which then occurred in the absence of caspase-3 activation. Iron loading was also associated with the formation of intracellular dinitrosyl-iron complexes (DNIC) upon NO exposure. Cytosolic preparations containing DNIC as well as pure preparations of DNIC suppressed caspase activity. These data suggest that non-heme iron content is a key factor in determining the consequence of NO on cell viability by regulating the chemical fate of NO.

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Section: Discussionmentioning

confidence: 99%

Cellular Non-heme Iron Content Is a Determinant of Nitric Oxide-mediated Apoptosis, Necrosis, and Caspase Inhibition

Kim¹,

Chung²,

Simmons³

et al. 2000

Journal of Biological Chemistry

224

131

View full text Add to dashboard Cite

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“…21 Although the role of β3-AR-mediated signaling in cardiomyocyte apoptosis is still unknown, it is possible that β3-AR exerts antiapoptotic effects through nitric oxide. 22 Several mechanisms of β-AR stimulation-induced apoptosis have been reported.…”

Section: β-Ar-mediated Apoptosis Of Cardiomyocytesmentioning

confidence: 99%

Apoptosis in Heart Failure - The Role of the .BETA.-Adrenergic Receptor-Mediated Signaling Pathway and p53-Mediated Signaling Pathway in the Apoptosis of Cardiomyocytes -

Fujita

Ishikawa

2011

Circ J

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The heart works as a driving force to deliver oxygen and nutrients to the whole body. Interrupting this function for only several minutes can cause critical and permanent damage to the human body. Thus, heart failure (HF) or attenuated cardiac function is an important factor that affects both patient's the quality of life and longevity. Numerous clinical and basic studies have been performed to clarify the complex pathophysiology of HF and to develop effective therapies. Modulating the β-adrenergic receptor-mediated signaling pathway has been one of the most crucial targets for HF therapy. Impressively, recent reports identified p53, a well-known tumor suppressor, as a major player in the development of HF. The present review highlights the apoptosis of cardiomyocytes, which is one of the important mechanisms that leads to HF and can be induced by both β-adrenergic signaling and p53. Consideration of the cross-talk among these major pathways will be important when developing effective and safe therapies for HF. (Circ J 2011; 75: 1811 - 1818

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“…Cytosolic extracts for caspase activation in itro were prepared from confluent cultures of chick embryo heart cells (CEHC), obtained and maintained as described in [24]. To prepare these extracts, the cells from 10-15 plates (10 cm diameter) were collected and washed in PBS.…”

Section: Cytosolic Extracts and Caspase Activationmentioning

confidence: 99%

“…In order to establish a cardiac cell-free model of apoptosis, we obtained cytosolic extracts from CEHC. These non-transformed heart cells can be easily obtained in large quantities, and express a high caspase activity, albeit usually latent [24]. Figure 5(A) shows that cytosolic extracts from CEHC represent a good model, with a very low degree of spontaneous caspase auto-activation.…”

Section: Figure 4 Spermine Causes the Rapid Release Of A Definite Amomentioning

confidence: 99%

Polyamines directly induce release of cytochrome c from heart mitochondria

Stefanelli

Stanic

Zini

et al. 2000

Biochemical Journal

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Cytochrome c release from mitochondria to the cytosol represents a critical step in apoptosis, correlated to the activation of the caspase cascade. In this report, we show that addition of micromolar concentrations of polyamines to isolated rat heart mitochondria induces the release of cytochrome c. Spermine, which is effective at concentrations of 10-100 μM, is more potent than spermidine, whereas putrescine has no effect up to 1 mM. The release of cytochrome c caused by spermine is a rapid, saturable and selective process that is independent of mitochondria damage. Spermine, unlike polylysine, is able to release a discrete amount of cytochrome c from intact, functional mitochondria. The cytochrome c-releasing power of spermine is not affected by cyclosporin A, differently from the effect of permeability transition inducers. In a cardiac cell-free model of apoptosis, the latent caspase activity of cytosolic extracts from cardiomyocytes could be activated by cytochrome c released from spermine-treated heart mitochondria. These data indicate a novel mechanism of cytochrome c release from the mitochondrion, and suggest that prolonged and sustained elevation of polyamines, characteristic of some pathologies such as heart hypertrophy, could be involved in the development of apoptosis.

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Nitric oxide can function as either a killer molecule or an antiapoptotic effector in cardiomyocytes

Cited by 47 publications

References 43 publications

Cellular Non-heme Iron Content Is a Determinant of Nitric Oxide-mediated Apoptosis, Necrosis, and Caspase Inhibition

Cellular Non-heme Iron Content Is a Determinant of Nitric Oxide-mediated Apoptosis, Necrosis, and Caspase Inhibition

Apoptosis in Heart Failure - The Role of the .BETA.-Adrenergic Receptor-Mediated Signaling Pathway and p53-Mediated Signaling Pathway in the Apoptosis of Cardiomyocytes -

Polyamines directly induce release of cytochrome c from heart mitochondria

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