title: The carboxyl terminus of heat shock protein 70-interacting protein (CHIP) participates in high glucose-induced cardiac injury.
abstract: The carboxyl terminus of heat shock protein 70-interacting protein (CHIP) is confirmed to have a protective effect on the myocardium, but its effect on diabetic cardiomyopathy is unclear. Small interfering RNA (siRNA) was used for knockdown experiments in neonatal rat cardiomyocytes to examine the function of CHIP in high glucose-induced injury. High glucose stimulated the production of reactive oxygen species (ROS), nicotinamide adenine dinucleotide phosphate oxidase (NOX), interleukin-1β (IL-1β), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) production. However, cardiomyocytes lacking CHIP suffered from increased oxidative stress and inflammatory responses. High glucose increased the expression of Bax and caspase-3 mRNAs, decreased the expression of Bcl-2 mRNA, and up-regulated the expression of the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) proteins. However, upon CHIP knockdown, the expression of Bax and caspase-3 mRNAs increased even further, and the expression of Bcl-2 mRNA was further suppressed. The expression of the phosphorylated p65 and p38 proteins (p-p65 and p-p38) was also further enhanced. Thus, CHIP is a potent cardioprotective molecule.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Xiong
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
authors.forename: Shiwen
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
authors.forename: Wenyao
authors.initials: W
authors.lastname: Cai
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Wen
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China. Electronic address: fyn1028@126.com.
authors.forename: Yongnan
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
authors.forename: Jingtian
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
authors.forename: Zeqi
authors.initials: Z
authors.lastname: Zheng
mesh_terms: D000818:Animals; D058065:Diabetic Cardiomyopathies / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D005947:Glucose / Q000633:toxicity; D006335:Heart Injuries / Q000139:chemically induced / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics*; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics*; D018384:Oxidative Stress / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics*
chemical_list: D009363:Neoplasm Proteins; D029543:Nucleocytoplasmic Transport Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; C063447:p65 oncofetal mRNA transport protein, rat; C467728:STUB1 protein, human; D044767:Ubiquitin-Protein Ligases; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose
keywords: CHIP; Cardiomyocytes; High glucose; NF-κB; ROS