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- Title
Elevated aldolase 1A, retrogene 1 expression induces cardiac apoptosis in rat experimental autoimmune myocarditis model.
- Authors
Choi, Seungmin; Chung, Joo Hee; Nam, Myung-Hee; Bang, Eunjung; Hong, Kwan Soo; Kim, Yong-Hwan; Seo, Jong Bok; Chi, Sung-Gil
- Abstract
Acute myocarditis is an unpredictable heart disease that is caused by inflammation-associated cell death. Although viral infection and drug exposure are known to induce acute myocarditis, the molecular basis for its development remains undefined. Using proteomics and molecular analyses in myosin-induced rat experimental autoimmune myocarditis (EAM), we identified that elevated expression of aldolase 1A, retrogene 1 (Aldoart1) is critical to induce mitochondrial dysfunction and acute myocarditis development. Here, we demonstrate that cardiac cell death is associated with increased expressions of proapoptotic genes in addition to high levels of glucose, lactate, and triglyceride in metabolite profiling. The functional protein association network analysis also suggests that Aldoart1 upregulation correlates with high levels of dihydroxyacetone kinase and triglyceride. In H9c2 cardiac cells, lipopolysaccharides (LPS) or high glucose exposure significantly increases the cytochrome c release and the conversion of pro-caspase 3 into the cleaved form of caspase 3. We also found that LPS- or glucose-induced toxicities are almost completely reversed by siRNA-mediated knockdown of Aldoartl, which consequently increases cell viability. Together, our study strongly suggests that Aldoart1 may be involved in inducing mitochondrial apoptotic processes and can be a novel therapeutic target to prevent the onset of acute myocarditis or cardiac apoptosis.
- Subjects
APOPTOSIS; CYTOCHROME c; CELL death; MYOSIN; HEART diseases; RATS; MYOCARDITIS
- Publication
Canadian Journal of Physiology & Pharmacology, 2020, Vol 98, Issue 6, p373
- ISSN
0008-4212
- Publication type
Article
- DOI
10.1139/cjpp-2019-0539