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dc.contributor.authorLiu, Jiao
dc.contributor.authorJin, Yuxuan
dc.contributor.authorWang, Bei
dc.contributor.authorWang, Yiran
dc.contributor.authorZuo, Shengkai
dc.contributor.authorZhang, Jinying
dc.date.accessioned2021-06-03T13:59:01Z
dc.date.available2021-06-03T13:59:01Z
dc.date.issued2021-05-16
dc.date.submitted2021-04-18
dc.identifier.citationLiu, J., Jin, Y., Wang, B., Wang, Y., Zuo, S., & Zhang, J. (2021). Dopamine D1 receptor alleviates doxorubicin-induced cardiac injury by inhibiting NLRP3 inflammasome. Biochemical and Biophysical Research Communications, 561, 7–13. doi:10.1016/j.bbrc.2021.04.098
dc.identifier.issn0006-291X
dc.identifier.pmid33992835
dc.identifier.doi10.1016/j.bbrc.2021.04.098
dc.identifier.urihttp://hdl.handle.net/10754/669366
dc.description.abstractDoxorubicin (DOX) is a broad-spectrum antineoplastic drug; however, its serious cardiotoxic side effects in inflammatory responses limit its use in clinical applications. Dopamine D1 receptor (DRD1), a G protein-coupled receptor, is crucial for the development and function of the nervous system; additionally, it also play a role in immune regulation. However, the specific role of DRD1 in DOX-induced cardiac inflammation has not yet been clarified. Here, we discovered that DRD1 expression was induced by DOX treatment in H9C2 cardiomyocytes. DRD1 activation by A-68930, a DRD1-specific agonist, decreased DOX-induced nucleotide-binding domain-like receptor protein 3 (NLRP3) expression, caspase-1 activation, and IL-1β maturation in H9C2 cells. Expression of the cytokines IL-1β and IL-18 in the supernatants was also inhibited by A-68930 treatment. DRD1 knockdown, using siRNA, abolished the effects of A-68930 on the DOX-induced NLRP3 inflammasome. Furthermore, we found that DRD1 signaling downregulated the NLRP3 inflammasome in H9C2 cells through cyclic adenosine monophosphate (cAMP). Moreover, application of A-68930 to activate DRD1 reduced cardiac injury and fibrosis in a DOX-treated mouse model by suppressing the NLRP3 inflammasome in the heart. These findings indicate that DRD1 signaling may protect against DOX-induced cardiac injury by inhibiting the NLRP3 inflammasome-mediated inflammation.
dc.description.sponsorshipAll authors thank Prof. Ying Yu (Tianjin Medical University) for the kindly support for our work. This work was supported by the China Postdoctoral Science Foundation (No.2019M652587), Nature Science Foundation of China (No. 81870328, U2004203), Henan Thousand Talents Program (No. ZYQR201912131).
dc.publisherElsevier BV
dc.relation.urlhttps://linkinghub.elsevier.com/retrieve/pii/S0006291X21007166
dc.rightsNOTICE: this is the author’s version of a work that was accepted for publication in Biochemical and biophysical research communications. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Biochemical and biophysical research communications, [561, , (2021-05-16)] DOI: 10.1016/j.bbrc.2021.04.098 . © 2021. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.titleDopamine D1 receptor alleviates doxorubicin-induced cardiac injury by inhibiting NLRP3 inflammasome.
dc.typeArticle
dc.contributor.departmentEnvironmental Science and Engineering Program
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.identifier.journalBiochemical and biophysical research communications
dc.rights.embargodate2022-05-13
dc.eprint.versionPost-print
dc.contributor.institutionDepartment of Cardiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
dc.contributor.institutionKey Laboratory of Cardiac Injury and Repair of Henan Province, Zhengzhou, Henan, China.
dc.contributor.institutionDepartment of Pharmacology and Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China
dc.identifier.volume561
dc.identifier.pages7-13
kaust.personWang, Yiran
dc.date.accepted2021-04-23
dc.identifier.eid2-s2.0-85105753775


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