Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jul 29:2020:2405135.
doi: 10.1155/2020/2405135. eCollection 2020.

Peroxiredoxin-1 Overexpression Attenuates Doxorubicin-Induced Cardiotoxicity by Inhibiting Oxidative Stress and Cardiomyocyte Apoptosis

Lai Jiang  1 , Yanping Gong  1 , Yida Hu  2 , Yangyang You  3 , Jiawu Wang  4 , Zhetao Zhang  5 , Zeyuan Wei  5 , Chaoliang Tang  4
Affiliations

Peroxiredoxin-1 Overexpression Attenuates Doxorubicin-Induced Cardiotoxicity by Inhibiting Oxidative Stress and Cardiomyocyte Apoptosis

Lai Jiang et al. Oxid Med Cell Longev. .

Abstract

Background. Previous research has shown that peroxiredoxin 1 (Prdx1) is an important modulator of physiological and pathophysiological cardiovascular events. This study is aimed at investigating the role and underlying mechanism of Prdx1 in doxorubicin- (DOX-) induced cardiotoxicity. Cardiac-specific expression of Prdx1 was induced in mice, and the mice received a single dose of DOX (15 mg/kg) to generate cardiotoxicity. First, our study demonstrated that Prdx1 expression was upregulated in the heart and in cardiomyocytes after DOX treatment. Second, we provided direct evidence that Prdx1 overexpression ameliorated DOX-induced cardiotoxicity by attenuating oxidative stress and cardiomyocyte apoptosis. Mechanistically, we found that DOX treatment increased the phosphorylation level of apoptosis signal-regulating kinase-1 (ASK1) and the downstream protein p38 in the heart and in cardiomyocytes, and these effects were decreased by Prdx1 overexpression. In contrast, inhibiting Prdx1 promoted DOX-induced cardiac injury via the ASK1/p38 pathway. These results suggest that Prdx1 may be an effective therapeutic option to prevent DOX-induced cardiotoxicity.

PubMed Disclaimer

Conflict of interest statement

No conflicts of interest are declared by the authors.

Figures

Figure 1
Figure 1
Prdx1 expression is increased in the heart and in cardiomyocytes after DOX treatment. (a) The protein and mRNA expression of Prdx1 in the heart 8 days after DOX treatment (n = 4, ∗P < 0.05 compared with the NS group). (b) The protein and mRNA expression of Prdx1 in cardiomyocytes treated with DOX (n = 4, ∗P < 0.05 compared with the PBS group).
Figure 2
Figure 2
Prdx1 overexpression protected against cardiac injury induced by DOX. (a) The protein levels of Prdx1 four weeks after AAV9-Prdx1 injection in mice (n = 4). (b, c) The results of body weight and HW/TL ratio measurements in mice (n = 6). (d–g) Biochemical determination of CK-MB and LDH levels in the heart and serum for the indicated groups (n = 6). (h) HE staining shows the pathological structure of the heart in mice (n = 5). ∗P < 0.05 compared with the NS group; #P < 0.05 compared with the DOX group.
Figure 3
Figure 3
Prdx1 overexpression attenuated cardiac dysfunction induced by DOX. (a, b) Echocardiographic parameters for each group (n = 8). (c–g) Hemodynamic parameters for each group (n = 6). ∗P < 0.05 compared with the NS group; #P < 0.05 compared with the DOX group.
Figure 4
Figure 4
Prdx1 overexpression attenuated oxidative stress induced by DOX. (a–d) Quantitative results for SOD, CAT, NADPH oxidase activity, and MDA content in the hearts of mice (n = 6). (e) Representative DHE staining images of the heart (n = 5). ∗P < 0.05 compared with the NS group; #P < 0.05 compared with the DOX group.
Figure 5
Figure 5
Prdx1 overexpression attenuated cardiomyocyte apoptosis induced by DOX. (a) Western blots showing the Bcl-2, Bax, and c-caspase3 levels in the hearts of mice (n = 4). (b) Representative TUNEL staining images of the heart (n = 5). ∗P < 0.05 compared with the NS group; #P < 0.05 compared with the DOX group.
Figure 6
Figure 6
Prdx1 overexpression relieves DOX-induced cardiotoxicity in vitro. (a–d) Quantitative results for SOD, CAT, NADPH oxidase activity, and MDA content in each group (n = 6). (e) Western blots showing the Bcl-2, Bax, and c-caspase3 levels in each group (n = 4). ∗P < 0.05 compared with the PBS group; #P < 0.05 compared with the DOX group.
Figure 7
Figure 7
Prdx1 overexpression inhibits ASK1/p38 pathway activation. (a) Western blots showing the p-ASK1, ASK1, p-p38, and p38 levels in the hearts of mice (n = 4). (b) Western blots showing the p-ASK1, ASK1, p-p38, and p38 levels in NVRMs (n = 4). ∗P < 0.05 compared with the NS or PBS group; #P < 0.05 compared with the DOX group.
Figure 8
Figure 8
Prdx1 inhibition exacerbated DOX-induced cardiotoxicity. (a–d) Quantitative results for SOD, CAT, NADPH oxidase activity, and MDA content in each group (n = 6). (e) Western blots showing the Bcl-2, Bax, and c-caspase3 levels in each group (n = 4). ∗P < 0.05 compared with the PBS+Ad-NC group; #P < 0.05 compared with the DOX+Ad-NC group; &P < 0.05 compared with the DOX+Ad-Prdx1 group.
Figure 9
Figure 9
Peroxiredoxin-1 overexpression attenuates doxorubicin-induced cardiotoxicity by inhibiting oxidative stress and cardiomyocyte apoptosis.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Campia U., Moslehi J. J., Amiri-Kordestani L., et al. Cardio-oncology: vascular and metabolic perspectives: a scientific statement from the American Heart Association. Circulation. 2019;139(13):e579–e602. doi: 10.1161/CIR.0000000000000641. - DOI - PMC - PubMed
    1. Herrmann J. Adverse cardiac effects of cancer therapies: cardiotoxicity and arrhythmia. Nature Reviews Cardiology. 2020;17(8):474–502. doi: 10.1038/s41569-020-0348-1. - DOI - PMC - PubMed
    1. Chen Y., Huang T., Shi W., Fang J., Deng H., Cui G. Potential targets for intervention against doxorubicin-induced cardiotoxicity based on genetic studies: a systematic review of the literature. Journal of Molecular and Cellular Cardiology. 2020;138:88–98. doi: 10.1016/j.yjmcc.2019.11.150. - DOI - PubMed
    1. Gorini S., De Angelis A., Berrino L., Malara N., Rosano G., Ferraro E. Chemotherapeutic drugs and mitochondrial dysfunction: focus on doxorubicin, trastuzumab, and sunitinib. Oxidative Medicine and Cellular Longevity. 2018;2018:15. doi: 10.1155/2018/7582730.7582730 - DOI - PMC - PubMed
    1. Carvalho F. S., Burgeiro A., Garcia R., Moreno A. J., Carvalho R. A., Oliveira P. J. Doxorubicin-induced cardiotoxicity: from bioenergetic failure and cell death to cardiomyopathy. Medicinal Research Reviews. 2014;34(1):106–135. doi: 10.1002/med.21280. - DOI - PubMed

LinkOut - more resources