Journal article
Energy-preserving effects of IGF-1 antagonize starvation-induced cardiac autophagy
Cardiovascular research, Vol.93(2), pp.320-329
02/01/2012
DOI: 10.1093/cvr/cvr321
PMCID: PMC3286200
PMID: 22135164
Abstract
Aims
Insulin-like growth factor 1 (IGF-1) is known to exert cardioprotective actions. However, it remains unknown if autophagy, a major adaptive response to nutritional stress, contributes to IGF-1-mediated cardioprotection.
Methods and results
We subjected cultured neonatal rat cardiomyocytes, as well as live mice, to nutritional stress and assessed cell death and autophagic rates. Nutritional stress induced by serum/glucose deprivation strongly induced autophagy and cell death, and both responses were inhibited by IGF-1. The Akt/mammalian target of rapamycin (mTOR) pathway mediated the effects of IGF-1 upon autophagy. Importantly, starvation also decreased intracellular ATP levels and oxygen consumption leading to AMP-activated protein kinase (AMPK) activation; IGF-1 increased mitochondrial Ca2+ uptake and mitochondrial respiration in nutrient-starved cells. IGF-1 also rescued ATP levels, reduced AMPK phosphorylation and increased p70S6K phosphorylation, which indicates that in addition to Akt/mTOR, IGF-1 inhibits autophagy by the AMPK/mTOR axis. In mice harbouring a liver-specific igf1 deletion, which dramatically reduces IGF-1 plasma levels, AMPK activity and autophagy were increased, and significant heart weight loss was observed in comparison with wild-type starved animals, revealing the importance of IGF-1 in maintaining cardiac adaptability to nutritional insults in vivo.
Conclusion
Our data support the cardioprotective actions of IGF-1, which, by rescuing the mitochondrial metabolism and the energetic state of cells, reduces cell death and controls the potentially harmful autophagic response to nutritional challenges. IGF-1, therefore, may prove beneficial to mitigate damage induced by excessive nutrient-related stress, including ischaemic disease in multiple tissues.
Details
- Title: Subtitle
- Energy-preserving effects of IGF-1 antagonize starvation-induced cardiac autophagy
- Creators
- Rodrigo Troncoso - 1 Centro de Estudios Moleculares de la Célula, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago 838-0492, ChileJose Miguel Vicencio - 1 Centro de Estudios Moleculares de la Célula, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago 838-0492, ChileValentina Parra - 1 Centro de Estudios Moleculares de la Célula, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago 838-0492, ChileAndriy Nemchenko - 2 Department of Internal Medicine (Cardiology Division), University of Texas Southwestern Medical Center, Dallas, TX 75235, USAYuki Kawashima - 3 Division of Pediatrics and Perinatology, Faculty of Medicine, Tottori University, 36-1 Nishicho, Yonago 683-8504, JapanAndrea del Campo - 1 Centro de Estudios Moleculares de la Célula, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago 838-0492, ChileBarbra Toro - 1 Centro de Estudios Moleculares de la Célula, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago 838-0492, ChilePavan K Battiprolu - 2 Department of Internal Medicine (Cardiology Division), University of Texas Southwestern Medical Center, Dallas, TX 75235, USAPablo Aranguiz - 1 Centro de Estudios Moleculares de la Célula, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago 838-0492, ChileMario Chiong - 1 Centro de Estudios Moleculares de la Célula, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago 838-0492, ChileShoshana Yakar - 4 Division of Endocrinology, Diabetes and Bone Diseases, Department of Medicine, The Mount Sinai School of Medicine, New York, NY 10029, USAThomas G Gillette - 2 Department of Internal Medicine (Cardiology Division), University of Texas Southwestern Medical Center, Dallas, TX 75235, USAJoseph A Hill - 2 Department of Internal Medicine (Cardiology Division), University of Texas Southwestern Medical Center, Dallas, TX 75235, USAEvan Dale Abel - 5 Program in Molecular Medicine and Division of Endocrinology, Metabolism, and Diabetes, University of Utah, School of Medicine, Salt Lake City, UT 84112, USADerek LeRoith - 6 Diabetes and Metabolism Clinical Research Center of Excellence, Technion University, Rambam- Health Care Campus, P.O.B 9602, Haifa 31096, IsraelSergio Lavandero - 1 Centro de Estudios Moleculares de la Célula, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago 838-0492, Chile
- Resource Type
- Journal article
- Publication Details
- Cardiovascular research, Vol.93(2), pp.320-329
- Publisher
- Oxford University Press
- DOI
- 10.1093/cvr/cvr321
- PMID
- 22135164
- PMCID
- PMC3286200
- ISSN
- 0008-6363
- eISSN
- 1755-3245
- Language
- English
- Date published
- 02/01/2012
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984024506602771
Metrics
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