The mechanism of RNA oxidation involved in the development of heart failure. (3rd August 2019)

• Record Type: Journal Article
• Authors: Liu, Tong; Cai, Jian-Ping; Zhang, Li-Qun; Sun, Ning; Cui, Ju; Wang, Hua; Yang, Jie-Fu
• Is Part Of: Free radical research. Volume 53:Number 8(2019)
• Page Start: 910
• Page End: 921
• Publication Date: 2019-08-03
• Subjects: 8-Hydroxyguanosine -- Dahl salt-sensitive rat -- heart failure -- RNA oxidation; Free radicals (Chemistry) -- Periodicals; Antioxidants -- Periodicals; Vitamin C -- Periodicals; Vitamin E -- Periodicals; 541.224
• DOI: 10.1080/10715762.2019.1646424
• Languages: English
• ISSNs: 1071-5762

Abstract

Abstract: Heart failure (HF) has become a global public health problem due to its unclear pathogenesis. Our previous studies have found that RNA oxidation is associated with the occurrence and development of a variety of chronic diseases in the elderly, but whether RNA oxidation is related to the pathogenesis of HF remains unclear. Male Dahl salt-sensitive rats (DSSR) were divided into 8% NaCl groups and 0.3% NaCl groups. The blood pressure of DSSR, HE staining of cardiac tissue, cardiac function index of colour Doppler echocardiography and plasma N-terminal probrain Natriuretic Peptide (NT-ProBNP) were used to evaluate the model making. The levels of 8-hydroxyguanosine (8-oxoGsn) and 8-hydroxydeoxyguanosine (8-oxodGsn) in myocardium and urine of DSSR were determined by high-performance liquid chromatography–mass spectrometry (LC-MS/MS). The expression of ERK-MAPK pathway and MTH1 was detected by Western blot (WB). Rats in the 8% NaCl group developed heart failure symptoms such as increased blood pressure, myocardial hypertrophy, decreased diastolic function, and increased plasma NT-ProBNP. The content of 8-oxoGsn in urine and heart tissue also increased, which was positively correlated with the related indicators of heart failure. This process is also accompanied by the sequential activation of ERK-MAPK pathway molecules and the increase of MTH1. The mechanism of RNA oxidation and inhibition is related to the occurrence and development of HF, which may be involved through ERK-MAPK pathway.