Glucose deprivation causes oxidative stress and stimulates aggresome formation and autophagy in cultured cardiac myocytes
| Autor: | Jessica Díaz-Elizondo, Paola Marambio, María Isabel Colombo, Daniela B. Munafó, Hugo Verdejo, Clara Quiroga, Barbra Toro, Sergio Lavandero, Guilermo Diaz-Araya, Mario Chiong, Rodrigo Troncoso, Roberto Bravo, Zully Pedrozo, Lorena García, Carlos Sanhueza, María-Julieta González, Valentina Parra |
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| Rok vydání: | 2009 |
| Předmět: |
Proteasome Endopeptidase Complex
Aggresome Protein aggregation Biology medicine.disease_cause Superoxide dismutase Adenosine Triphosphate Microscopy Electron Transmission Tubulin medicine Autophagy Myocyte Animals HSP70 Heat-Shock Proteins Myocytes Cardiac Molecular Biology Cells Cultured chemistry.chemical_classification Inclusion Bodies Reactive oxygen species Superoxide Dismutase Ubiquitin Catalase Glutathione Cardiac myocytes Hsp70 Cell biology Acetylcysteine Rats Oxidative Stress Protein Transport Glucose chemistry biology.protein Molecular Medicine Protein Multimerization Reactive Oxygen Species Oxidative stress Microtubule-Organizing Center |
| Zdroj: | Biochimica et biophysica acta. 1802(6) |
| ISSN: | 0006-3002 |
| Popis: | Aggresomes are dynamic structures formed when the ubiquitin–proteasome system is overwhelmed with aggregation-prone proteins. In this process, small protein aggregates are actively transported towards the microtubule-organizing center. A functional role for autophagy in the clearance of aggresomes has also been proposed. In the present work we investigated the molecular mechanisms involved on aggresome formation in cultured rat cardiac myocytes exposed to glucose deprivation. Confocal microscopy showed that small aggregates of polyubiquitinated proteins were formed in cells exposed to glucose deprivation for 6 h. However, at longer times (18 h), aggregates formed large perinuclear inclusions (aggresomes) which colocalized with γ-tubulin (a microtubule-organizing center marker) and Hsp70. The microtubule disrupting agent vinblastine prevented the formation of these inclusions. Both small aggregates and aggresomes colocalized with autophagy markers such as GFP-LC3 and Rab24. Glucose deprivation stimulates reactive oxygen species (ROS) production and decreases intracellular glutathione levels. ROS inhibition by N-acetylcysteine or by the adenoviral overexpression of catalase or superoxide dismutase disrupted aggresome formation and autophagy induced by glucose deprivation. In conclusion, glucose deprivation induces oxidative stress which is associated with aggresome formation and activation of autophagy in cultured cardiac myocytes. |
| Databáze: | OpenAIRE |
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