Protein kinase A signals apoptotic activation in glucose-deprived hepatocytes: participation of reactive oxygen species
| Autor: | Maria C. Larocca, Cristián Favre, Anabela Ferretti, Stella Maris Mattaloni, Justina E. Ochoa |
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| Rok vydání: | 2012 |
| Předmět: |
Mitochondrial ROS
Male Cancer Research medicine.medical_specialty Cell Survival Clinical Biochemistry Pharmaceutical Science Apoptosis Biology Mitochondrion medicine.disease_cause Cytosol Superoxide Dismutase-1 Internal medicine medicine Cyclic AMP Animals Rats Wistar Protein kinase A Cells Cultured bcl-2-Associated X Protein Pharmacology chemistry.chemical_classification Reactive oxygen species Sulfonamides L-Lactate Dehydrogenase Caspase 3 Superoxide Dismutase Biochemistry (medical) Cytochromes c Cell Biology Catalase Isoquinolines Cyclic AMP-Dependent Protein Kinases Cell biology Mitochondria Rats Oxidative Stress Protein Transport Endocrinology Enzyme Glucose chemistry Hepatocytes Signal transduction Reactive Oxygen Species Oxidative stress Signal Transduction |
| Zdroj: | Apoptosis : an international journal on programmed cell death. 17(5) |
| ISSN: | 1573-675X |
| Popis: | Glucose deprivation entails oxidative stress and apoptosis in diverse cell types. Liver tissue shows high tolerance to nutritional stress, however regulation of survival in normal hepatocytes subjected to glucose restriction is unclear. We assessed the survival response of cultured hepatocytes subjected to glucose deprivation and analyzed the putative participation of protein kinase A (PKA) in this response. Six hours glucose deprivation induced a PKA dependent activation of apoptosis in cultured hepatocytes, without having an impact on non apoptotic death. Apoptotic activation associated to glucose restriction was secondary to an imbalance in cellular reactive oxygen species (ROS). In this condition, PKA inhibition led to an early prevention in mitochondrial ROS production and a late increase in scavenging enzymes transcript levels. These results supported the hypothesis that PKA could modulate glucose deprivation induced apoptotic activation by conditioning mitochondrial ROS production during glucose fasting. We presented additional evidence sustaining this model: First, glucose withdrawal led to a 95% increase in mitochondrial cAMP levels in cultured hepatocytes; second, activation of PKA significantly augmented hepatic mitochondrial ROS generation, whereas PKA inhibition elicited the opposite effect. Mitochondrial PKA signaling, previously proposed as an autonomic pathway adjusting respiration rate, emerges as a mechanism of controlling cell survival during glucose restriction. |
| Databáze: | OpenAIRE |
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