Glucose deprivation causes oxidative stress and stimulates aggresome formation and autophagy in cultured cardiac myocytes

Paola Marambio; Barbra Toro; Carlos Sanhueza; Rodrigo Troncoso; Valentina Parra; Hugo Verdejo; Lorena García; Clara Quiroga; Daniela Munafo; Jessica Díaz-Elizondo; Roberto Bravo; María Julieta González; Guilermo Diaz-Araya; Zully Pedrozo; Mario Chiong; María Isabel Colombo; Sergio Lavandero

doi:10.1016/j.bbadis.2010.02.002

Glucose deprivation causes oxidative stress and stimulates aggresome formation and autophagy in cultured cardiac myocytes

Paola Marambio, Barbra Toro, Carlos Sanhueza, Rodrigo Troncoso, Valentina Parra, Hugo Verdejo, Lorena García, Clara Quiroga, Daniela Munafo, Jessica Díaz-Elizondo, Roberto Bravo, María Julieta González, Guilermo Diaz-Araya, Zully Pedrozo, Mario Chiong, María Isabel Colombo, Sergio Lavandero

Universidad de Chile

Research output: Contribution to journal › Article › peer-review

102 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	509-518
Number of pages	10
Journal	Biochimica et Biophysica Acta - Molecular Basis of Disease
Volume	1802
Issue number	6
DOIs	https://doi.org/10.1016/j.bbadis.2010.02.002
Publication status	Published - Jun 2010

Bibliographical note

Funding Information:
This work was supported by FONDAP (Fondo de Areas Prioritarias, Chile) grant 15010006 to S.L. and Fondo Mejoramiento de la Calidad de la Educacion Superior (MECESUP) UCHO802 . B.T., C.S, R.T., V.P., C.Q, J.D.E., R.B. and Z.P. hold Ph.D. fellowships from CONICYT, Chile. We thank to Dr Sharon A Tooze (London Research Institute, Cancer Research UK) for her kind donation of the adenovirus LC3-GFP. We also thank to Fidel Albornoz and Ruth Marquez for their excellent technical assistance. The authors deny any conflicts of interest in this work. S.L. is in a sabbatical leave at the University of Texas Southwestern Medical Center, Dallas, Texas, USA. Appendix A

Funding

This work was supported by FONDAP (Fondo de Areas Prioritarias, Chile) grant 15010006 to S.L. and Fondo Mejoramiento de la Calidad de la Educacion Superior (MECESUP) UCHO802 . B.T., C.S, R.T., V.P., C.Q, J.D.E., R.B. and Z.P. hold Ph.D. fellowships from CONICYT, Chile. We thank to Dr Sharon A Tooze (London Research Institute, Cancer Research UK) for her kind donation of the adenovirus LC3-GFP. We also thank to Fidel Albornoz and Ruth Marquez for their excellent technical assistance. The authors deny any conflicts of interest in this work. S.L. is in a sabbatical leave at the University of Texas Southwestern Medical Center, Dallas, Texas, USA. Appendix A

Funders	Funder number
FONDAP	15010006
Fondo Mejoramiento de la Calidad de la Educacion Superior
MECESUP	UCHO802

ASJC Scopus Subject Areas

Molecular Medicine
Molecular Biology

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10.1016/j.bbadis.2010.02.002

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Marambio, P., Toro, B., Sanhueza, C., Troncoso, R., Parra, V., Verdejo, H., García, L., Quiroga, C., Munafo, D., Díaz-Elizondo, J., Bravo, R., González, M. J., Diaz-Araya, G., Pedrozo, Z., Chiong, M., Colombo, M. I., & Lavandero, S. (2010). Glucose deprivation causes oxidative stress and stimulates aggresome formation and autophagy in cultured cardiac myocytes. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1802(6), 509-518. https://doi.org/10.1016/j.bbadis.2010.02.002

Marambio, P, Toro, B, Sanhueza, C, Troncoso, R, Parra, V, Verdejo, H, García, L, Quiroga, C, Munafo, D, Díaz-Elizondo, J, Bravo, R, González, MJ, Diaz-Araya, G, Pedrozo, Z, Chiong, M, Colombo, MI & Lavandero, S 2010, 'Glucose deprivation causes oxidative stress and stimulates aggresome formation and autophagy in cultured cardiac myocytes', Biochimica et Biophysica Acta - Molecular Basis of Disease, vol. 1802, no. 6, pp. 509-518. https://doi.org/10.1016/j.bbadis.2010.02.002

@article{aadd2bea753e41379ce2cfde494eb036,

title = "Glucose deprivation causes oxidative stress and stimulates aggresome formation and autophagy in cultured cardiac myocytes",

abstract = "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.",

author = "Paola Marambio and Barbra Toro and Carlos Sanhueza and Rodrigo Troncoso and Valentina Parra and Hugo Verdejo and Lorena Garc{\'i}a and Clara Quiroga and Daniela Munafo and Jessica D{\'i}az-Elizondo and Roberto Bravo and Gonz{\'a}lez, {Mar{\'i}a Julieta} and Guilermo Diaz-Araya and Zully Pedrozo and Mario Chiong and Colombo, {Mar{\'i}a Isabel} and Sergio Lavandero",

note = "Funding Information: This work was supported by FONDAP (Fondo de Areas Prioritarias, Chile) grant 15010006 to S.L. and Fondo Mejoramiento de la Calidad de la Educacion Superior (MECESUP) UCHO802 . B.T., C.S, R.T., V.P., C.Q, J.D.E., R.B. and Z.P. hold Ph.D. fellowships from CONICYT, Chile. We thank to Dr Sharon A Tooze (London Research Institute, Cancer Research UK) for her kind donation of the adenovirus LC3-GFP. We also thank to Fidel Albornoz and Ruth Marquez for their excellent technical assistance. The authors deny any conflicts of interest in this work. S.L. is in a sabbatical leave at the University of Texas Southwestern Medical Center, Dallas, Texas, USA. Appendix A ",

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T1 - Glucose deprivation causes oxidative stress and stimulates aggresome formation and autophagy in cultured cardiac myocytes

AU - Marambio, Paola

AU - Toro, Barbra

AU - Sanhueza, Carlos

AU - Troncoso, Rodrigo

AU - Parra, Valentina

AU - Verdejo, Hugo

AU - García, Lorena

AU - Quiroga, Clara

AU - Munafo, Daniela

AU - Díaz-Elizondo, Jessica

AU - Bravo, Roberto

AU - González, María Julieta

AU - Diaz-Araya, Guilermo

AU - Pedrozo, Zully

AU - Chiong, Mario

AU - Colombo, María Isabel

AU - Lavandero, Sergio

N1 - Funding Information: This work was supported by FONDAP (Fondo de Areas Prioritarias, Chile) grant 15010006 to S.L. and Fondo Mejoramiento de la Calidad de la Educacion Superior (MECESUP) UCHO802 . B.T., C.S, R.T., V.P., C.Q, J.D.E., R.B. and Z.P. hold Ph.D. fellowships from CONICYT, Chile. We thank to Dr Sharon A Tooze (London Research Institute, Cancer Research UK) for her kind donation of the adenovirus LC3-GFP. We also thank to Fidel Albornoz and Ruth Marquez for their excellent technical assistance. The authors deny any conflicts of interest in this work. S.L. is in a sabbatical leave at the University of Texas Southwestern Medical Center, Dallas, Texas, USA. Appendix A

PY - 2010/6

Y1 - 2010/6

N2 - 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.

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Glucose deprivation causes oxidative stress and stimulates aggresome formation and autophagy in cultured cardiac myocytes

Abstract

Bibliographical note

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ASJC Scopus Subject Areas

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