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The mechanism of RNA oxidation involved in the development of heart failure.

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.
AuthorsTong Liu, Jian-Ping Cai, Li-Qun Zhang, Ning Sun, Ju Cui, Hua Wang, Jie-Fu Yang
JournalFree radical research (Free Radic Res) Vol. 53 Issue 8 Pg. 910-921 (Aug 2019) ISSN: 1029-2470 [Electronic] England
PMID31401895 (Publication Type: Journal Article)
Chemical References
  • Nudt1 protein, rat
  • Guanosine
  • 8-hydroxyguanosine
  • RNA
  • 8-Hydroxy-2'-Deoxyguanosine
  • Pyrophosphatases
Topics
  • 8-Hydroxy-2'-Deoxyguanosine (analysis)
  • Animals
  • Chromatography, Liquid
  • Gene Expression Regulation
  • Guanosine (analogs & derivatives, analysis)
  • Heart Failure (genetics, metabolism)
  • Humans
  • MAP Kinase Signaling System
  • Male
  • Myocardium (metabolism)
  • Oxidation-Reduction
  • Pyrophosphatases (genetics, metabolism)
  • RNA (chemistry, metabolism)
  • Rats
  • Tandem Mass Spectrometry

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