Open Access Research article

Proteomic and biochemical analyses reveal the activation of unfolded protein response, ERK-1/2 and ribosomal protein S6 signaling in experimental autoimmune myocarditis rat model

Joo Hee Chung12, Hee Jung Choi3, Soo Young Kim1, Kwan Soo Hong4, Soo Kee Min5, Myung Hee Nam1, Chan Wha Kim2, Young Ho Koh3* and Jong Bok Seo1*

Author Affiliations

1 Seoul Center, Korea Basic Science Institute, Sungbuk-gu, Seoul 136-713, Republic of Korea

2 BK21 School of Life Sciences & Biotechnology, Korea University, Sungbuk-gu, Seoul 136-701, Republic of Korea

3 ILSONG Institute of Life Science, Hallym University, 1605-4 Gwanyangdong, Anyang, Gyeonggi-do 431-060, Republic of Korea

4 Division of MR Research, Korea Basic Science Institute, Cheongwon 363-883, Republic of Korea

5 Department of Pathology, Hallym Sacred Heart Hospital, Hallym University Medical School, 1605-4 Gwanyangdong, Anyang, Gyeonggi-do 431-060, Republic of Korea

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BMC Genomics 2011, 12:520  doi:10.1186/1471-2164-12-520

Published: 20 October 2011



To investigate the molecular and cellular pathogenesis underlying myocarditis, we used an experimental autoimmune myocarditis (EAM)-induced heart failure rat model that represents T cell mediated postinflammatory heart disorders.


By performing unbiased 2-dimensional electrophoresis of protein extracts from control rat heart tissues and EAM rat heart tissues, followed by nano-HPLC-ESI-QIT-MS, 67 proteins were identified from 71 spots that exhibited significantly altered expression levels. The majority of up-regulated proteins were confidently associated with unfolded protein responses (UPR), while the majority of down-regulated proteins were involved with the generation of precursor metabolites and energy metabolism in mitochondria. Although there was no difference in AKT signaling between EAM rat heart tissues and control rat heart tissues, the amounts and activities of extracellular signal-regulated kinase (ERK)-1/2 and ribosomal protein S6 (rpS6) were significantly increased. By comparing our data with the previously reported myocardial proteome of the Coxsackie viruses of group B (CVB)-mediated myocarditis model, we found that UPR-related proteins were commonly up-regulated in two murine myocarditis models. Even though only two out of 29 down-regulated proteins in EAM rat heart tissues were also dysregulated in CVB-infected rat heart tissues, other proteins known to be involved with the generation of precursor metabolites and energy metabolism in mitochondria were also dysregulated in CVB-mediated myocarditis rat heart tissues, suggesting that impairment of mitochondrial functions may be a common underlying mechanism of the two murine myocarditis models.


UPR, ERK-1/2 and S6RP signaling were activated in both EAM- and CVB-induced myocarditis murine models. Thus, the conserved components of signaling pathways in two murine models of acute myocarditis could be targets for developing new therapeutic drugs or methods aimed at treating enigmatic myocarditis.