Salusin-β contributes to oxidative stress and inflammation in diabetic cardiomyopathy.
Salusin-β accelerates inflammatory responses in vascular endothelial cells, and increases oxidative stress in vascular smooth muscle cells. Plasma salusin-β levels were increased in diabetic patients. This study was designed to determine whether salusin-β is involved in the pathogenesis of diabetic cardiomyopathy (DCM), and whether knockdown of salusin-β attenuates cardiac inflammation and oxidative stress in rats with DCM. H9c2 or neonatal rat cardiomyocytes were incubated with 33.3 mM of glucose to mimic the high glucose (HG) in diabetes. Streptozotocin and high-fat diet were used to induce type 2 diabetes in rats. HG induced salusin-β expression in H9c2 cells. Salusin-β caused greater responses of oxidative stress, NFκB activation and inflammation in HG-treated H9c2 cells than these in control H9c2 cells. Diphenyleneiodonium (a NAD(P)H oxidase inhibitor) or N-acetylcysteine (an antioxidant) inhibited the salusin-β-induced NFκB activation and inflammation. Bay11-7082 (a NFκB inhibitor) attenuated salusin-β-induced inflammation but not oxidative stress. Knockdown of salusin-β prevented the HG-induced oxidative stress, NFκB activation and inflammation in neonatal rat cardiomyocytes. Silencing salusin-β with adenoviruse-mediated shRNA had no significant effects on blood glucose and insulin resistance, but attenuated ventricular dysfunction in diabetic rats. Oxidative stress, NFκB activation, inflammation, salusin-β upregulation in myocardium of diabetic rats were prevented by knockdown of salusin-β. These results indicate that salusin-β contributes to inflammation in DCM via NOX2/ROS/NFκB signaling, and that knockdown of salusin-β attenuates cardiac dysfunction, oxidative stress and inflammation in DCM.
Department of Physiology, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, China.
Ming-Xia
MX
Zhao
Department of Physiology, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, China.
Bing
B
Zhou
Department of Physiology, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, China.
Li
L
Ling
Department of Physiology, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, China.
Xiao-Qing
XQ
Xiong
Department of Physiology, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, China.
Feng
F
Zhang
Department of Pathophysiology, Nanjing Medical University, Nanjing, China.
Qi
Q
Chen
Department of Pathophysiology, Nanjing Medical University, Nanjing, China.
Yue-Hua
YH
Li
Department of Physiology and Pathophysiology, Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an, China.
Yu-Ming
YM
Kang
Department of Physiology, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, China.|Department of Pathophysiology, Nanjing Medical University, Nanjing, China.
Guo-Qing
0000-0002-3132-9592
GQ
Zhu
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D058065:Diabetic Cardiomyopathies / Q000378:metabolism* / Q000473:pathology; D059305:Diet, High-Fat / Q000009:adverse effects; D005786:Gene Expression Regulation / Q000502:physiology; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology*; D007333:Insulin Resistance / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
D001786:Blood Glucose; D036341:Intercellular Signaling Peptides and Proteins; D016328:NF-kappa B; C528274:salusin-beta, rat