Elevated Levels of Oxidative DNA Damage in Serum and Myocardium of Patients With Heart Failure

Kono, Yasuyuki; Nakamura, Kazufumi; Kimura, Hideo; Nishii, Nobuhiro; Watanabe, Atsuyuki; Banba, Kimikazu; Miura, Aya; Nagase, Satoshi; Sakuragi, Satoru; Kusano, Kengo; Matsubara, Hiromi; Ohe, Tohru

doi:10.1253/circj.70.1001

Cited by 88 publications

(63 citation statements)

References 34 publications

(16 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore in present study, we investigated 8-OHdG which is one of the most abundant oxidative DNA products and a sensitive DNA damage marker and found increased oxidative DNA damage in the serum of patients with AMI, so oxidative stress is also a condition under which DNA damage occurs. In agreement with previous studies, our results showed an increase in p53 and 8-OHdG in the circulation [23,24]. Furthermore, the bcl-2 gene family is a complex network regulating apoptosis which some of the candidates can suppress apoptosis while the others can induce it [50].…”

Section: Discussionsupporting

confidence: 93%

See 1 more Smart Citation

The role of p53, bax, bcl2, and 8-OHdG in human acute myocardial infarction

et al. 2010

View full text Add to dashboard Cite

Apoptosis is implicated in unfavorable remodeling of the left ventricle during acute myocardial infarction (AMI). Both DNA damage and p53 play important roles in regulating apoptosis. Expression patterns of apoptotic regulating genes such as p53, bax, and bcl-2 highlight the importance of inhibiting ventricle remodeling and subsequent injuries. In the present study, serum levels of p53 and 8-hydroxy-2-deoxyguanosine (8-OHdG) as well as p53, bax, and bcl-2 expression were examined after the onset of AMI in Iranian patients. Serum levels of p53 and 8-OHdG were measured by enzyme-linked immunosorbent assay (ELISA) and the presence of p53 protein and mRNA expression of p53, bax, and bcl-2 were analyzed by Western blotting and real time RT-PCR methods respectively. In patients presenting with AMI, serum levels of p53 and 8-OHdG were increased in comparison to healthy controls. Likewise, transcripts of p53 and bax were also elevated in patients while bcl-2 was decreased. Collectively, our data suggest the novel use of p53 and 8-OHdG as markers of apoptosis and DNA damage following AMI. Our results also revealed that apoptosis occurs in concert with an up-regulation of p53 and bax and a down-regulation of bcl-2 which may suggest a possible therapeutic intervention in patients recovering from AMI.© Versita Sp. z o.o.

show abstract

Section: Discussionsupporting

confidence: 93%

“…The most reliable serum markers of apoptosis and oxidative DNA damage are p53 and 8-OHdG respectively [23,24]. Evidence of apoptosis is provided by p53-stimulated transcription of the proapoptotic bax gene [25][26][27], and repression of the antiapoptotic bcl-2 gene [25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

The role of p53, bax, bcl2, and 8-OHdG in human acute myocardial infarction

et al. 2010

View full text Add to dashboard Cite

show abstract

“…The most reliable biomarker of oxidative DNA damage and repair in aging, 4,5) carcinogenesis, 19) and cardiovascular [20][21][22] and cerebrovascular 23) diseases is 8-OHdG. Here, we immunohistochemically demonstrated the presence of 8-OHdG in myocytes at all times tested in the I/R-injured rat hearts, and quantitative immunohistochemical measurement showed that levels were significantly increased in hearts with treated I/R injury.…”

Section: Discussionmentioning

confidence: 59%

Determination of Oxidative Stress and Cardiac Dysfunction after Ischemia/Reperfusion Injury in Isolated Rat Hearts

Ichikawa

Kuniyoshi

Yamashiro

et al. 2013

Ann Thorac Cardiovasc Surg

View full text Add to dashboard Cite

Background: Oxidative stress due to reactive oxygen species (ROS) is thought to play a considerable role in ischemia/reperfusion (I/R) injury that impairs cardiac function. The present study examined oxidative damage in I/R injury and investigated the correlation between oxidative stress and impaired cardiac function after I/R injury of the isolated rat heart. Methods: Hearts isolated from male Sprague-Dawley rats were mounted on a Langendorff apparatus. Hearts arrested using St. Thomas cardioplegic solution and then they were reperfused. The hearts were divided into three groups depending on the frequency (0-2) of I/R. After I/R, left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), positive maximum left ventricular developing pressure (max LV dP/dt) and coronary flow (CF) were measured. Creatine kinase (CK) was measured in the coronary effluent and 8-hydroxy-2'deoxyguanosine (8OHdG), a marker of oxidative DNA damage, was measured. Adenosine triphosphate (ATP) was measured from frozen myocardial tissue after experiment. Results: We immunohistochemically demonstrated and quantified levels of 8-OHdG after I/ R injury of the heart. The frequency of I/R injury and cardiac dysfunction significantly and negatively correlated. The ATP products were similar among the three groups. The incidence of ventricular arrhythmias was not by affected oxidative stress. Conclusion: The frequency of I/R injury had more of an effect on 8-OHdG products and on impaired cardiac function with less myocyte damage than ischemic duration within 30 minutes of ischemia.Keywords: oxidative stress, ischemia/reperfusion injury, 8-hydroxy-2'deoxyguanosine (8OHdG), cardiac dysfunction tion might cause negative effects and a worse prognosis, with myocardial dysfunction (stunning) and coronary noreflow phenomenon. 1) Reactive oxygen species (ROS), which can be produced from reperfusion of the ischemic myocardium 2) and Ca 2 + overload in myocytes, contribute to cardiac ischemia/reperfusion (I/R) injury. 3)Reactive oxygen species cause the oxidation of DNAs, membranous phospholipids and proteins, and these are implicated in the pathogenesis of I/R injury, degenerative disease, carcinogenesis and aging. In particular, ROS have the potential to injure cardiac myocytes, endothelial cells and initiate chemical reactions in myocardial I/R injury.

show abstract

“…47,48) Although the relevance of oxidative DNA damage to heart failure has been clearly demonstrated in doxorubicin-induced cardiomyopathy (discussed above), it is unknown whether DNA damage is the cause of heart failure.…”

Section: Dna Damage Causes Heart Failurementioning

confidence: 99%

Heart Failure as an Aging-Related Phenotype

Morita

Komuro

2018

Int. Heart J.

View full text Add to dashboard Cite

SummaryThe molecular pathophysiology of heart failure, which is one of the leading causes of mortality, is not yet fully understood. Heart failure can be regarded as a systemic syndrome of aging-related phenotypes. Wnt/β-catenin signaling and the p53 pathway, both of which are key regulators of aging, have been demonstrated to play a critical role in the pathogenesis of heart failure. Circulating C1q was identified as a novel activator of Wnt/β-catenin signaling, promoting systemic aging-related phenotypes including sarcopenia and heart failure. On the other hand, p53 induces the apoptosis of cardiomyocytes in the failing heart. In these molecular mechanisms, the cross-talk between cardiomyocytes and non-cardiomyocytes (e,g,. endothelial cells, fibroblasts, smooth muscle cells, macrophages) deserves mentioning. In this review, we summarize recent advances in the understanding of the molecular pathophysiology underlying heart failure, focusing on Wnt/β-catenin signaling and the p53 pathway.(Int Heart J 2018; 59: 6-13)

show abstract

Elevated Levels of Oxidative DNA Damage in Serum and Myocardium of Patients With Heart Failure

Cited by 88 publications

References 34 publications

The role of p53, bax, bcl2, and 8-OHdG in human acute myocardial infarction

The role of p53, bax, bcl2, and 8-OHdG in human acute myocardial infarction

Determination of Oxidative Stress and Cardiac Dysfunction after Ischemia/Reperfusion Injury in Isolated Rat Hearts

Heart Failure as an Aging-Related Phenotype

Contact Info

Product

Resources

About