Hypoxia/reoxygenation induces apoptosis through biphasic induction of protein synthesis in cultured rat brain neurons

Bossenmeyer, Carine; Chihab, Rifki; Müller, S.; Schroeder, Henri; Daval, Jean‐Luc

doi:10.1016/s0006-8993(97)01527-8

Cited by 64 publications

(25 citation statements)

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“…Indeed, neuronal cells cultured in chemically defined medium have proven to mimic morphologic, electrophysiological, and neurochemical development and differentiation occurring in vivo (7,8), and such a preparation provides the advantage of investigating cellular responses inherent to a single variable. By using cultured neurons from the developing rat forebrain as a model, we have previously demonstrated that transient oxygen deprivation may trigger neuronal death through an apoptotic process that requires specific and time-dependent changes in protein synthesis (9,10), a conclusion supported by other studies (6,11).…”

mentioning

confidence: 58%

“…All animal experimentation was performed with the standards of animal care and housing, according to the NIH Guide for the Care and Use of Laboratory Animals, and was approved by the local institutional board (Bureau de la Protection Animale). Primary cultured neurons were obtained from 14-d-old rat embryo forebrains as previously described (9,27). When they were in the proestrus period, as shown by the observation of daily vaginal smears, Sprague Dawley female rats (R. Janvier, Le Genest-St-Isle, France) were housed together with males for 24 h, and pregnant dams were maintained in separate cages for 14 d under standard laboratory conditions on a 12 h/12 h light/dark cycle (lights on at 0600 h) with food and water available ad libitum.…”

Section: Methodsmentioning

confidence: 99%

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Bilirubin Exerts Additional Toxic Effects in Hypoxic Cultured Neurons from the Developing Rat Brain by the Recruitment of Glutamate Neurotoxicity

et al. 2001

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Both hypoxia and bilirubin are common risk factors in newborns, which may act synergistically to produce anatomical and functional disturbances of the CNS. Using primary cultures of neurons from the fetal rat brain, it was recently reported that neuronal apoptosis accounts for the deleterious consequences of these two insults. To investigate the influence of hypoxia, bilirubin, or their combination on the outcome of neuronal cells of the immature brain, and delineate cellular mechanisms involved, 6-d-old cultured neurons were submitted to either hypoxia (6 h), unconjugated bilirubin (0.5 M), or to combined conditions. Within 96 h, cell viability was reduced by 22.7% and 24.5% by hypoxia and bilirubin, respectively, whereas combined treatments decreased vital score by 34%. Nuclear morphology revealed 13.4% of apoptotic cells after hypoxia, 16.2% after bilirubin, and 22.6% after both treatments. Bilirubin action was specifically blocked by the glutamate receptor antagonist MK-801, which was without effect on the consequences of hypoxia. Cerebral hypoxia remains a significant risk for neonatal morbidity and mortality, as well as long-term neurologic sequelae such as cerebral palsy, mental retardation, or seizure disorders (1, 2). Although lack of oxygen has been associated with neuronal degeneration (3, 4), it was not clear whether hypoxia itself, without the influence of combined ischemia, kills brain cells. In contrast to studies in intact animals, which are often difficult to interpret due to a number of confounding variables, cell culture seems a useful tool for elucidating cellular and molecular mechanisms involved in clinical disorders such as cerebral hypoxia (5, 6). Indeed, neuronal cells cultured in chemically defined medium have proven to mimic morphologic, electrophysiological, and neurochemical development and differentiation occurring in vivo (7,8), and such a preparation provides the advantage of investigating cellular responses inherent to a single variable. By using cultured neurons from the developing rat forebrain as a model, we have previously demonstrated that transient oxygen deprivation may trigger neuronal death through an apoptotic process that requires specific and time-dependent changes in protein synthesis (9, 10), a conclusion supported by other studies (6, 11).Bilirubin constitutes another potential cause of brain injury (12, 13). Hyperbilirubinemia is still a common concern in neonatology, especially in the care of low birth weight prema- ABSTRACT 507

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confidence: 58%

Section: Methodsmentioning

confidence: 99%

Bilirubin Exerts Additional Toxic Effects in Hypoxic Cultured Neurons from the Developing Rat Brain by the Recruitment of Glutamate Neurotoxicity

et al. 2001

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“…It has been reported that hypoxia=reoxygenation injury involved a number of factors, including reactive oxygen species, nitric oxide, oxygen free radical, N-methyl-Daspartate, intracellular free calcium, and protein kinase C (Cazevieille et al, 1993;Yun et al, 1997;Bossenmeyer, 1998;Wang & Shum, 2002). But recently, most researchers consider oxidative stress as a major factor after hypoxia=reoxygenation injury (Cazevieille et al, 1993;Chan, 1996;Yun et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Salidroside on Hypoxia/Reoxygenation Injury by Sodium Hydrosulfite in PC12 Cells

Chen

Lü

Wang

et al. 2007

Pharmaceutical Biology

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Hypoxia=reoxygenation causes cellular injury and death associated with many pathophysiologic conditions, including respiratory disorders, myocardial ischemia, and tumour progression diseases. Neuronal pheochromocytoma (PC12) cells are widely used as a model system for neurologic research and are subject to chemical hypoxia induced with sodium hydrosulfite (Na 2 S 2 O 4 ), a common oxygen-consuming agent. Salidroside, which is the main active component of the famous traditional Chinese herb Rhodiola rosea L. (Crassulaceae), has been proved to possess many bioactivities. In this article, we studied the protective effects of salidroside on hypoxia= reoxygenation injury in PC12 cells induced by Na 2 S 2 O 4 . Cultures of PC12 cells were exposed for 1 h to 10 mM Na 2 S 2 O 4 for hypoxia, followed by reoxygenation for 2 h. The results showed that salidroside was very stable in medium and was not harmful to PC12 cells at the experimental concentrations of 0 $ 200 mg=mL. The cytoprotection by salidroside was dose-dependent, and the cell viability was 41.8 AE 5.7%, 62.4 AE 4.1%, and 92.2 AE 3.7% at 0, 50, and 100 mg=mL of salidroside, respectively. The level of released LDH significantly decreased from 513.5 AE 5.5% (without salidroside) to 258.1 AE 6.3% (with 100 mg=mL salidroside). Flow cytometry was performed to measure apoptotic rate. The results of flow cytometry assay indicated that the apoptotic rate was 17.0 AE 1.2% after hypoxia=reoxygenation injury. When the cells were treated with salidroside 12.5, 50 and 100 mg=mL, the apoptotic rate was 9.5 AE 0.9%, 7.4 AE 0.5%, and 4.5 AE 0.4%, respectively. In addition, our results were confirmed by inspection of cell morphology of PC12 cells. Treatment with salidroside (12.5, 50, 100 mg=mL) significantly prevented the cells from morphologic changes. All the above results showed salidroside could effectively protect PC12 cell against hypoxia=reoxygenation injury.

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“…Proapoptotic Bax and the interleukin-converting enzyme subfamily of caspases increased after exposure of neurons to hypoxia followed by reoxygenation (8). Induction of Bax and p53 expression preceded neuronal apoptotic death.…”

Section: Apoptosismentioning

confidence: 95%

Reactive species mechanisms of cellular hypoxia-reoxygenation injury

Jackson

2002

American Journal of Physiology-Cell Physiology

937

673

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Li, Chuanyu, and Robert M. Jackson. Reactive species mechanisms of cellular hypoxia-reoxygenation injury. Am J Physiol Cell Physiol 282: C227-C241, 2002; 10.1152/ajpcell.00112.2001.-Exacerbation of hypoxic injury after restoration of oxygenation (reoxygenation) is an important mechanism of cellular injury in transplantation and in myocardial, hepatic, intestinal, cerebral, renal, and other ischemic syndromes. Cellular hypoxia and reoxygenation are two essential elements of ischemia-reperfusion injury. Activated neutrophils contribute to vascular reperfusion injury, yet posthypoxic cellular injury occurs in the absence of inflammatory cells through mechanisms involving reactive oxygen (ROS) or nitrogen species (RNS). Xanthine oxidase (XO) produces ROS in some reoxygenated cells, but other intracellular sources of ROS are abundant, and XO is not required for reoxygenation injury. Hypoxic or reoxygenated mitochondria may produce excess superoxide (O 2 Ϫ ) and release H2O2, a diffusible long-lived oxidant that can activate signaling pathways or react vicinally with proteins and lipid membranes. This review focuses on the specific roles of ROS and RNS in the cellular response to hypoxia and subsequent cytolytic injury during reoxygenation.anoxia; ischemia; reperfusion BACKGROUND

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Hypoxia/reoxygenation induces apoptosis through biphasic induction of protein synthesis in cultured rat brain neurons

Cited by 64 publications

References 55 publications

Bilirubin Exerts Additional Toxic Effects in Hypoxic Cultured Neurons from the Developing Rat Brain by the Recruitment of Glutamate Neurotoxicity

Bilirubin Exerts Additional Toxic Effects in Hypoxic Cultured Neurons from the Developing Rat Brain by the Recruitment of Glutamate Neurotoxicity

Protective Effects of Salidroside on Hypoxia/Reoxygenation Injury by Sodium Hydrosulfite in PC12 Cells

Reactive species mechanisms of cellular hypoxia-reoxygenation injury

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