Beclin-1-Dependent Autophagy Protects the Heart During Sepsis

Circulation
Yuxiao SunQun S Zang

Abstract

Cardiac dysfunction is a major component of sepsis-induced multiorgan failure in critical care units. Changes in cardiac autophagy and its role during sepsis pathogenesis have not been clearly defined. Targeted autophagy-based therapeutic approaches for sepsis are not yet developed. Beclin-1-dependent autophagy in the heart during sepsis and the potential therapeutic benefit of targeting this pathway were investigated in a mouse model of lipopolysaccharide (LPS)-induced sepsis. LPS induced a dose-dependent increase in autophagy at low doses, followed by a decline that was in conjunction with mammalian target of rapamycin activation at high doses. Cardiac-specific overexpression of Beclin-1 promoted autophagy, suppressed mammalian target of rapamycin signaling, improved cardiac function, and alleviated inflammation and fibrosis after LPS challenge. Haplosufficiency for beclin 1 resulted in opposite effects. Beclin-1 also protected mitochondria, reduced the release of mitochondrial danger-associated molecular patterns, and promoted mitophagy via PTEN-induced putative kinase 1-Parkin but not adaptor proteins in response to LPS. Injection of a cell-permeable Tat-Beclin-1 peptide to activate autophagy improved cardiac function, atte...Continue Reading

References

Aug 2, 2000·Proceedings of the National Academy of Sciences of the United States of America·R K Bruick
Sep 2, 2003·Biochimica Et Biophysica Acta·Erik M Schwiebert, Akos Zsembery
Dec 6, 2003·Proceedings of the National Academy of Sciences of the United States of America·Zhenyu YueNathaniel Heintz
Jun 3, 2004·Nature Reviews. Immunology·Seung-Yong Seong, Polly Matzinger
Jun 24, 2005·The American Journal of Pathology·Masashi TamaokiToshimichi Yoshida
Sep 28, 2005·The Journal of Cell Biology·Sovan SarkarDavid C Rubinsztein
Apr 29, 2006·Cell Death and Differentiation·A Hamacher-BradyA B Gustafsson
Jun 22, 2006·Endocrine, Metabolic & Immune Disorders Drug Targets·Derek C AngusEliezer Silva
Dec 22, 2006·The Journal of Biological Chemistry·Sovan SarkarDavid C Rubinsztein
Mar 27, 2007·Surgical Infections·Qun ZangJureta W Horton
Apr 24, 2007·The Biochemical Journal·Dieter A KubliAsa B Gustafsson
Jul 4, 2007·The Journal of Clinical Investigation·Hongxin ZhuJoseph A Hill
Sep 26, 2007·Cell Research·Yang Cao, Daniel J Klionsky
Feb 19, 2008·The Journal of Biological Chemistry·Huafeng ZhangGregg L Semenza
Apr 9, 2008·Nature Chemical Biology·Andrea WilliamsDavid C Rubinsztein
Aug 16, 2008·Circulation Research·Kazuhiko NishidaKinya Otsu
Sep 16, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Dieter A KubliAsa B Gustafsson
Oct 10, 2008·Molecular Biology of the Cell·Eisuke ItakuraNoboru Mizushima
Dec 23, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Hua YuanRoberta A Gottlieb
Feb 4, 2009·Laboratory Investigation; a Journal of Technical Methods and Pathology·Eizo WatanabeRichard S Hotchkiss
Feb 28, 2009·International Immunology·Taro Kawai, Shizuo Akira
Mar 10, 2009·Nature Cell Biology·Kohichi MatsunagaTamotsu Yoshimori
Jul 28, 2009·Current Opinion in Critical Care·Sergio L Zanotti-Cavazzoni, Steven M Hollenberg
Oct 9, 2009·Journal of Cell Science·Mathieu Laplante, David M Sabatini
Jan 9, 2010·Cell Death and Differentiation·S MichiorriG Casari
Jan 20, 2010·FEBS Letters·Chang Hwa JungDo-Hyung Kim
Mar 30, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Qun S ZangFiemu E Nwariaku
Sep 3, 2010·Nature Cell Biology·Noboru Mizushima, Beth Levine
Nov 23, 2010·Nature Reviews. Immunology·Grace Y Chen, Gabriel Nuñez
Jan 21, 2011·Nature·Beth LevineHerbert W Virgin
Mar 18, 2011·Annals of Surgery·Chi-Hsun HsiehYa-Ching Hsieh
Mar 19, 2011·Current Opinion in Cardiology·Min XieJoseph A Hill
Dec 16, 2011·Autophagy·Ellen WirawanPeter Vandenabeele

❮ Previous
Next ❯

Citations

Feb 13, 2019·Cells·Yuxiao SunQun S Zang
Feb 23, 2019·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·You WuZhong-Qiu Lu
Oct 28, 2019·Journal of Cachexia, Sarcopenia and Muscle·Martina BaraldoBert Blaauw
Sep 11, 2019·Cardiovascular Research·Nina KaludercicJulio Madrigal-Matute
Mar 21, 2020·Frontiers in Pharmacology·Huan LinHongsheng Ren
Sep 10, 2020·Frontiers in Medicine·Tamara MerzOscar McCook
Dec 14, 2018·Cell Proliferation·Zeng ZhaolinWang Zuo
Jul 28, 2019·Proceedings of the National Academy of Sciences of the United States of America·Anthony OrvedahlHerbert W Virgin
Oct 17, 2019·DNA and Cell Biology·Mengfei ChenYanxuan Gong
Jun 13, 2020·Frontiers in Physiology·Justin M Quiles, Åsa B Gustafsson
Jul 10, 2019·Current Pharmaceutical Design·Ying TanMaolong Dong
Jan 8, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Bing XiaYaohong Zhu
Feb 23, 2020·International Journal of Molecular Sciences·Ruizhu Lin, Risto Kerkelä
Dec 12, 2019·Scientific Reports·Marine FerronBenjamin Lauzier
Sep 12, 2019·Frontiers in Physiology·Xin YinLiheng Guo
Mar 7, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Leroy C JosephJohn P Morrow
Dec 8, 2020·Frontiers in Physiology·Sumita MishraMark J Ranek
Dec 29, 2020·EMBO Molecular Medicine·Leandro R SoriaNicola Brunetti-Pierri
Apr 12, 2020·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Tianxiao DuanPeng Luo
Nov 28, 2020·International Immunopharmacology·Wenting WangHongsheng Ren
Jan 26, 2021·Movement Disorders : Official Journal of the Movement Disorder Society·Chi-Un ChoeTanja Zeller
Aug 28, 2020·Free Radical Biology & Medicine·Ning LiQizhu Tang
Jan 1, 2021·BioMed Research International·Qian-Wei LiXiao-Qing Zhang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiology Journals

Discover the latest cardiology research in this collection of the top cardiology journals.

Autophagy & Disease

Autophagy is an important cellular process for normal physiology and both elevated and decreased levels of autophagy are associated with disease. Here is the latest research.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms