Effects of chronic ethanol exposure on acetaldehyde and free radical production by astrocytes in culture

Eysseric, Hélène; Gonthier, B.; Soubeyran, A.; Richard, M J; Daveloose, Denis; Barret, L.

doi:10.1016/s0741-8329(00)00075-6

Cited by 30 publications

(17 citation statements)

References 37 publications

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“…5). Acetaldehyde accumulation can occur by other pathways, including catalase-mediated acetaldehyde production (Eysseric et al, 2000). We therefore measured the accumulation of acetaldehyde after treatment of hepatocytes with ethanol.…”

Section: Acetaldehyde Stimulation Of P42/44 Mapk and Jnkmentioning

confidence: 99%

Temporal Activation of p42/44 Mitogen-Activated Protein Kinase and c-Jun N-Terminal Kinase by Acetaldehyde in Rat Hepatocytes and Its Loss after Chronic Ethanol Exposure

Lee¹,

Aroor²,

Shukla³

2002

J Pharmacol Exp Ther

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Several cell-damaging effects of ethanol are due to its major metabolite acetaldehyde but its mechanisms are not known. We have studied the effect of acetaldehyde on p42/44 mitogenactivated protein kinase (MAPK) and p46/p54 c-Jun N-terminal kinase (JNK 1/2) in rat hepatocytes. Acetaldehyde caused peak activation of p42/44 MAPK at 10 min followed by JNK activation at 1 h. These responses were acetaldehyde dose-dependent (0.2-5 mM). There was a consistently higher activation of p46 JNK than p54 JNK. Ethanol also activated both p42/44 MAPK and p46/p54 JNK. The activation of JNK by ethanol, however, was not significantly affected by treatment of hepatocytes with 4-methylpyrazole, an alcohol dehydrogenase inhibitor. Cells treated with 200 mM ethanol for 1 h accumulated 0.35 Ϯ 0.02 mM acetaldehyde, but the magnitude of JNK activation was greater than that expected with 0.35 mM acetaldehyde. Thus, ethanol-activated JNK may be both acetaldehyde-dependent and -independent. The activation of JNK by ethanol or acetaldehyde was insensitive to the treatment of hepatocytes with genistein (tyrosine kinase inhibitor) and 2-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)maleimide (GF109203X) (protein kinase C inhibitor). Remarkably, in contrast to the above-mentioned effects on normal hepatocytes, acetaldehyde was unable to increase JNK activity in hepatocytes isolated from rats chronically fed ethanol for 6 weeks and indicated a loss of this acetaldehyde response. Thus, temporal activation of the p42/44 MAPK and p46/p54 JNK, the greater activation of p46 JNK than p54 JNK, and loss of JNK activation after chronic ethanol exposure indicate that these kinases are differentially affected by ethanol metabolite acetaldehyde.

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Section: Acetaldehyde Stimulation Of P42/44 Mapk and Jnkmentioning

confidence: 99%

Temporal Activation of p42/44 Mitogen-Activated Protein Kinase and c-Jun N-Terminal Kinase by Acetaldehyde in Rat Hepatocytes and Its Loss after Chronic Ethanol Exposure

Lee¹,

Aroor²,

Shukla³

2002

J Pharmacol Exp Ther

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“…Astrocytes respond with an increase in the intracellular free-Ca 2 + concentration ([Ca 2 + ] c ) after stimulation with a variety of neurotransmitters, neuromodulators, and hormones. They play an important role in the developmental guidance of migrating neurons, in the regulation of neurotransmitter and ion levels, in the nutrition of neurons, and in the production of neurotrophic factors (Eysseric et al, 2000). Furthermore, astrocytes communicate with other surrounding astrocytes and neurons, and thereby regulate the neuronal activity and synaptic neurotransmission (Araque et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Ebselen Alters Mitochondrial Physiology and Reduces Viability of Rat Hippocampal Astrocytes

Santofimia‐Castaño

Salido

González

2013

DNA and Cell Biology

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The seleno-organic compound and radical scavenger ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) have been extensively employed as an anti-inflammatory and neuroprotective compound. However, its glutathione peroxidase activity at the expense of cellular thiols groups could underlie certain deleterious actions of the compound on cell physiology. In this study, we have analyzed the effect of ebselen on rat hippocampal astrocytes in culture. Cellular viability, the intracellular free-Ca 2 + concentration ([Ca 2 + ] c ), the mitochondrial freeCa 2 + concentration ([Ca 2 + ] m ), and mitochondrial membrane potential (c m ) were analyzed. The caspase-3 activity was also assayed. Our results show that cell viability was reduced by treatment of cells with ebselen, depending on the concentration employed. In the presence of ebselen, we observed an initial transient increase in [Ca 2 + ] c that was then followed by a progressive increase to an elevated plateau. We also observed a transient increase in [Ca 2 + ] m in the presence of ebselen that returned toward a value over the prestimulation level. The compound induced depolarization of c m and altered the permeability of the mitochondrial membrane. Additionally, a disruption of the mitochondrial network was observed. Finally, we did not detect changes in caspase-3 activation in response to ebselen treatment. Collectively, these data support the likelihood of ebselen, depending on the concentration employed, reduces viability of rat hippocampal astrocytes via its action on the mitochondrial activity. These may be early effects that do not involve caspase-3 activation. We conclude that, depending on the concentration used, ebselen might exert deleterious actions on astrocyte physiology that could compromise cell function.

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“…Ethanol metabolism is responsible for generation of reactive oxidant species (ROS) that cause tissue damage and affect a wide range of organ systems [1][2][3]. Some of its effects are directly due to either ethanol or its metabolites, whereas others are related to nutritional deficiencies associated with alcohol intake.…”

Section: Introductionmentioning

confidence: 99%

Changes in Serum Retinol, α-Tocopherol, Vitamin C, Carotenoids, Zinc and Selenium after Micronutrient Supplementation during Alcohol Rehabilitation

Guéguen

Pirollet²,

Leroy

et al. 2003

Journal of the American College of Nutrition

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Effects of chronic ethanol exposure on acetaldehyde and free radical production by astrocytes in culture

Cited by 30 publications

References 37 publications

Temporal Activation of p42/44 Mitogen-Activated Protein Kinase and c-Jun N-Terminal Kinase by Acetaldehyde in Rat Hepatocytes and Its Loss after Chronic Ethanol Exposure

Temporal Activation of p42/44 Mitogen-Activated Protein Kinase and c-Jun N-Terminal Kinase by Acetaldehyde in Rat Hepatocytes and Its Loss after Chronic Ethanol Exposure

Ebselen Alters Mitochondrial Physiology and Reduces Viability of Rat Hippocampal Astrocytes

Changes in Serum Retinol, α-Tocopherol, Vitamin C, Carotenoids, Zinc and Selenium after Micronutrient Supplementation during Alcohol Rehabilitation

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