Hepatoprotective effect of endogenous nitric oxide during ischemia-reperfusion in the rat

Cottart, Charles‐Henry; Do, Louis; Blanc, M; Vaubourdolle, Michel; Descamps, Géraldine; Durand, Dominique; Galen, F. X.; Clot, Jean-Pierre

doi:10.1002/hep.510290317

Cited by 114 publications

(85 citation statements)

References 24 publications

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“…(42,43) In cardiomyocytes, hepatocytes, and endothelial cells, NO preconditioning was shown to have antiapoptotic effects in ischemia and reperfusion injury. (12) This study further showed that NO preconditioning produces antiapoptotic effects on oxidative stress-induced osteoblast apoptosis. Bcl-X L contributes to the protection of NO pretreatment from oxidative stress-induced apoptotic insults to osteoblasts.…”

Section: Discussionmentioning

confidence: 63%

“…(11) In ischemia and reperfusion injury, NO preconditioning was shown to produce protective effects on cardiomyocytes, hepatocytes, and endothelial cells. (12) Our previous studies showed that pretreatment with NO protects osteoblasts from oxidative stress-induced apoptotic insults via a mitochondriondependent mechanism. (8,13) Thus NO preconditioning may be applied as a cell model to investigate the survival signals or as an effective treatment of inflammation-induced bone diseases.…”

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confidence: 99%

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GATA-3 transduces survival signals in osteoblasts through upregulation of bcl-x L gene expression

Chen

Lin

Chou

2010

Journal of Bone and Mineral Research

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GATA-3, a transcription factor, participates in regulating cell development, proliferation, and death. This study was aimed at evaluating the roles of GATA-3 in protecting osteoblasts against oxidative stress-induced apoptotic insults and their possible mechanisms. Pretreatment with nitric oxide (NO) for 24 hours protected osteoblasts, prepared from neonatal rat calvaria, against oxidative stressinduced apoptotic insults. Such protection involved enhancement of Bcl-X L messenger (m)RNA and protein syntheses and the translocation of this antiapoptotic protein from the cytoplasm to mitochondria. GATA-3 was detected in rat osteoblasts, and GATA-3-specific DNA-binding elements exist in the promoter region of the bcl-x L gene. NO preconditioning attenuated oxidative stress-caused suppression of GATA-3 mRNA and protein synthesis and the translocation of this transcription factor from the cytoplasm to nuclei. Application of GATA-3 small interfering (si)RNA into osteoblasts decreased the levels of this transcription factor and simultaneously inhibited Bcl-X L mRNA synthesis. Pretreatment with NO lowered the oxidative stress-caused alteration in the binding of GATA-3 to its specific DNA motifs. Oxidative stress-inhibited Runx2 mRNA expression, but NO preconditioning decreased such inhibition. NO pretreatment time-dependently enhanced the association of GATA-3 with Runx2. Knocking down the translation of GATA-3 using RNA interference significantly decreased the protection of NO preconditioning against oxidative stress-induced alterations of cell morphologies, DNA fragmentation, and cell apoptosis. In comparison, overexpression of GATA-3 could promote NO preconditioning-involved Bcl-X L expression and cell survival. Therefore, this study shows that GATA-3 plays critical roles in mediating survival signals in osteoblasts, possibly through upregulating bcl-x L gene expression. ß

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Section: Discussionmentioning

confidence: 63%

mentioning

confidence: 99%

GATA-3 transduces survival signals in osteoblasts through upregulation of bcl-x L gene expression

Chen

Lin

Chou

2010

Journal of Bone and Mineral Research

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“…40,41 Consistently, stimulation of NO production improves blood perfusion in preconditioned livers. 42 However, there is no indication that NO modulates hepatocyte response to hypoxia.…”

Section: Discussionmentioning

confidence: 82%

Ischemic preconditioning reduces Na+ accumulation and cell killing in isolated rat hepatocytes exposed to hypoxia

et al. 2000

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Short periods of ischemia followed up by reperfusion are known to protect the heart against injury caused by a subsequent sustained ischemia. This phenomenon, known as ischemic preconditioning, has also been recently shown to reduce ischemic liver damage, but the mechanisms involved are still unknown. By using isolated hepatocytes as an in vitro model of liver preconditioning, we have investigated the possible effect of preconditioning on intracellular pH and Na ؉ homeostasis. Freshly isolated rat hepatocytes were preconditioned by 10 minutes of incubation under hypoxic conditions followed up by 10 minutes of reoxygenation and subsequently exposed to 90 minutes of hypoxia. Although preconditioning did not ameliorate adenosine triphosphate (ATP) depletion, preconditioned hepatocytes exhibited an increased resistance to cell killing during hypoxic incubation. Intracellular acidosis and Na ؉ accumulation developing during hypoxia were appreciably reduced in preconditioned cells. The effects of preconditioning on intracellular pH, Na ؉ homeostasis, and citotoxicity were mimicked by stimulating protein kinase C (PKC) with 4␤-phorbol-12-myristate-13-acetate (PMA) or 1,2 dioctanoyl-glycerol (1,2 DOG). Conversely, inhibiting PKC with chelerythrine or blocking vacuolar proton ATPase (V-ATPase) with bafilomycin A 1 abolished the protection given by preconditioning or by PMA treatment on hypoxic acidosis, Na ؉ overload, and hepatocyte killing. Similarly, the addition of Na ؉ ionophore monensin also reverted the cytoprotection exerted by preconditioning. This indicated that ischemic preconditioning of isolated hepatocytes decreased cell killing during hypoxia by preventing intracellular Na ؉ accumulation. We propose that, after preconditioning, the stimulation of PKC might activate proton extrusion through V-ATPase, thus, limiting intracellular acidosis and Na ؉ overload promoted by Na ؉ -dependent acid buffering systems. (HEPATOLOGY 2000;31:166-172.)In 1986, Murry et al. 1 reported that a short period of ischemia led to an unexpected resistance of the myocardium to a subsequent prolonged ischemia. Since then, the resistance to ischemic injury acquired after 1 or more brief periods of ischemia followed up by reperfusion has been termed ischemic preconditioning. 1,2 In the myocardium, ischemic preconditioning occurs in 2 phases: an early phase (early preconditioning) that immediately follows the transient hypoxia and lasts 2 to 3 hours, and a late phase (late preconditioning) that begins 12 to 24 hours from the transient ischemia and lasts for 3 to 4 days. 3 Besides the heart, ischemic preconditioning has been shown in several organs including the brain, the skeletal muscles, and the small intestine. 3 Recently, the development of preconditioning has also been observed in livers exposed to brief interruptions of blood perfusion. [4][5][6] Hepatic preconditioning prevents hepatocellular damage caused by both warm and cold ischemia and improves liver transplantation in rats. [4][5][6] Extensive studies in the myocardium have s...

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“…18,19 In ischemia and reperfusion injury, NO preconditioning was shown to produce protective effects on cardiomyocytes, hepatocytes, and endothelial cells. 20 It was suggested that NO is a mediator of estrogen action on bone in ovariectomized rats. 21 In this study, we used neonatal rat calvarial osteoblasts as the experimental model to evaluate the effects of the NO pretreatment on oxidative stress-induced cellular insults and the possible mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Nitric oxide protects osteoblasts from oxidative stress‐induced apoptotic insults via a mitochondria‐dependent mechanism

Chang

Liao

Lin

et al. 2006

Journal Orthopaedic Research

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Nitric oxide (NO) contributes to the regulation of osteoblast activities. In this study, we evaluated the protective effects of NO pretreatment on oxidative stress-induced osteoblast apoptosis and its possible mechanism using neonatal rat calvarial osteoblasts as the experimental model. Exposure of osteoblasts to sodium nitroprusside (SNP) at a low concentration of 0.3 mM significantly increased cellular NO levels without affecting cell viability. However, when the concentration reached a high concentration of 2 mM, SNP increased the levels of intracellular reactive oxygen species and induced osteoblast injuries. Thus, administration of 0.3 and 2 mM SNP in osteoblasts were respectively used as sources of NO and oxidative stress. Pretreatment with NO for 24 h significantly ameliorated the oxidative stress-caused morphological alterations and decreases in alkaline phosphatase activity, and reduced cell death. Oxidative stress induced osteoblast death via an apoptotic mechanism, but NO pretreatment protected osteoblasts against the toxic effects. The mitochondrial membrane potential was significantly reduced following exposure to the oxidative stress. However, pretreatment with NO significantly lowered the suppressive effects. Oxidative stress increased cellular Bax protein production and cytochrome c release from mitochondria. Pretreatment with NO significantly decreased oxidative stress-caused augmentation of Bax and cytochrome c protein levels. In parallel with cytochrome c release, oxidative stress induced caspase-3 activation and DNA fragmentation. Pretreatment with NO significantly reduced the oxidative stress-enhanced caspase-3 activation and DNA damage. Results of this study show that NO pretreatment can protect osteoblasts from oxidative stress-induced apoptotic insults. The protective action involves a mitochondria-dependent mechanism. ß

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Hepatoprotective effect of endogenous nitric oxide during ischemia-reperfusion in the rat

Abstract: The aim of this study was to evaluate the protective or deleterious effects of endogenous nitric oxide (NO) on liver cells during hepatic ischemia-reperfusion (IR) in the rat.

Cited by 114 publications

References 24 publications

GATA-3 transduces survival signals in osteoblasts through upregulation of bcl-x L gene expression

GATA-3 transduces survival signals in osteoblasts through upregulation of bcl-x L gene expression

Ischemic preconditioning reduces Na+ accumulation and cell killing in isolated rat hepatocytes exposed to hypoxia

Nitric oxide protects osteoblasts from oxidative stress‐induced apoptotic insults via a mitochondria‐dependent mechanism

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