title: Comparative proteomics reveals abnormal binding of ATGL and dysferlin on lipid droplets from pressure overload-induced dysfunctional rat hearts.
abstract: Excessive retention of neutral lipids in cardiac lipid droplets (LDs) is a common observation in cardiomyopathy. Thus, the systematic investigation of the cardiac LD proteome will help to dissect the underlying mechanisms linking cardiac steatosis and myocardial dysfunction. Here, after isolation of LDs from normal and dysfunctional Sprague-Dawley rat hearts, we identified 752 heart-associated LD proteins using iTRAQ quantitative proteomic method, including 451 proteins previously unreported on LDs. The most noteworthy finding was the identification of the membrane resealing protein, dysferlin. An analysis of dysferlin truncation mutants indicated that its C2 domain was responsible for its LD localization. Quantitative proteomic results further determined that 27 proteins were increased and 16 proteins were decreased in LDs from post pressure overload-induced dysfunctional hearts, compared with normal hearts. Notably, adipose triacylglycerol lipase (ATGL) was dramatically decreased and dysferlin was substantially increased on dysfunctional cardiac LDs. This study for the first time reveals the dataset of the heart LD proteome in healthy tissue and the variation of it under cardiac dysfunction. These findings highlight an association between the altered LD protein localization of dysferlin and ATGL and myocardial dysfunction.
authors.affiliation: Department of Anesthesiology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.|National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Linghai
authors.initials: L
authors.lastname: Li
authors.affiliation: Beijing An Zhen Hospital, Capital Medical University, Key Laboratory of Upper Airway Dysfunction-related Cardiovascular Diseases, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing, China.|National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Huina
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Cardiovascular Diseases, Civil Aviation General Hospital, Peking University, Beijing, China.
authors.forename: Weiyi
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejang University, Hangzhou, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Hong
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Jifeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Shuyan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Shimeng
authors.initials: S
authors.lastname: Xu
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Shu
authors.affiliation: Department of Cardiology, Affiliated Hospital of Guilin Medical University, Guilin, China.
authors.forename: Juanfen
authors.initials: J
authors.lastname: Li
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Fuquan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejang University, Hangzhou, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Department of Cardiology, Affiliated Hospital of Guilin Medical University, Guilin, China.
authors.forename: Zongjie
authors.initials: Z
authors.lastname: Qian
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Pingsheng
authors.initials: P
authors.lastname: Liu
mesh_terms: D000818:Animals; D006321:Heart / Q000502:physiology* / Q000503:physiopathology; D008049:Lipase / Q000378:metabolism*; D066292:Lipid Droplets / Q000378:metabolism*; D013058:Mass Spectrometry; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D009124:Muscle Proteins / Q000737:chemistry / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D011312:Pressure; D011485:Protein Binding; D000072417:Protein Domains; D060066:Protein Interaction Maps; D020543:Proteome / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013347:Subcellular Fractions / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D000217:Acyltransferases
chemical_list: D008049:Lipase; D008565:Membrane Proteins; D009124:Muscle Proteins; D020543:Proteome; D014280:Triglycerides; C547052:Dysf protein, rat; C571275:PNPLA2 protein, rat; D000217:Acyltransferases