title: Salt-induced changes in cardiac phosphoproteome in a rat model of chronic renal failure.
abstract: Heart damage is widely present in patients with chronic kidney disease. Salt diet is the most important environmental factor affecting development of chronic renal failure and cardiovascular diseases. The proteins involved in chronic kidney disease -induced heart damage, especially their posttranslational modifications, remain largely unknown to date. Sprague-Dawley rats underwent 5/6 nephrectomy (chronic renal failure model) or sham operation were treated for 2 weeks with a normal-(0.4% NaCl), or high-salt (4% NaCl) diet. We employed TiO2 enrichment, iTRAQ labeling and liquid-chromatography tandem mass spectrometry strategy for phosphoproteomic profiling of left ventricular free walls in these animals. A total of 1724 unique phosphopeptides representing 2551 non-redundant phosphorylation sites corresponding to 763 phosphoproteins were identified. During normal salt feeding, 89 (54%) phosphopeptides upregulated and 76 (46%) phosphopeptides downregulated in chronic renal failure rats relative to sham rats. In chronic renal failure rats, high salt intake induced upregulation of 84 (49%) phosphopeptides and downregulation of 88 (51%) phosphopeptides. Database searches revealed that most of the identified phospholproteins were important signaling molecules such as protein kinases, receptors and phosphatases. These phospholproteins were involved in energy metabolism, cell communication, cell differentiation, cell death and other biological processes. The Search Tool for the Retrieval of Interacting Genes analysis revealed functional links among 15 significantly regulated phosphoproteins in chronic renal failure rats compared to sham group, and 23 altered phosphoproteins induced by high salt intake. The altered phosphorylation levels of two proteins involved in heart damage, lamin A and phospholamban were validated. Expression of the downstream genes of these two proteins, desmin and SERCA2a, were also analyzed.
authors.affiliation: Division of Nephrology, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Guangzhou, Guangdong, China.
authors.forename: Zhengxiu
authors.initials: Z
authors.lastname: Su
authors.affiliation: Division of Nephrology, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Guangzhou, Guangdong, China.
authors.forename: Hongguo
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Division of Nephrology, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Guangzhou, Guangdong, China.
authors.forename: Menghuan
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Division of Nephrology, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Guangzhou, Guangdong, China.
authors.forename: Liangliang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Division of Nephrology, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Guangzhou, Guangdong, China.
authors.forename: Hanchang
authors.initials: H
authors.lastname: He
authors.affiliation: Division of Nephrology, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Guangzhou, Guangdong, China.
authors.forename: Shaoling
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Division of Nephrology, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Guangzhou, Guangdong, China.
authors.forename: Fan Fan
authors.initials: FF
authors.lastname: Hou
authors.affiliation: Division of Nephrology, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Guangzhou, Guangdong, China.
authors.forename: Aiqing
authors.initials: A
authors.lastname: Li
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004032:Diet; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D063990:Gene Ontology; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D034904:Lamin Type A / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009392:Nephrectomy; D010748:Phosphopeptides / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D060066:Protein Interaction Maps / Q000187:drug effects; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*; D000099211:Phospholamban
chemical_list: D002135:Calcium-Binding Proteins; D034904:Lamin Type A; D010748:Phosphopeptides; D010750:Phosphoproteins; D020543:Proteome; D017673:Sodium Chloride, Dietary; D000099211:Phospholamban