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C-Reactive Protein Inhibits Survivin Expression via Akt/mTOR Pathway Downregulation by PTEN Expression in Cardiac Myocytes.

 Beom Seob Lee  ;  Soo Hyuk Kim  ;  Jaewon Oh  ;  Taewon Jin  ;  Eun Young Choi  ;  Sungha Park  ;  Sang-Hak Lee  ;  Ji Hyung Chung  ;  Seok-Min Kang 
 PLOS ONE, Vol.9(5) : e98113, 2014 
Journal Title
Issue Date
Animals ; Animals, Newborn ; Blotting, Western ; C-Reactive Protein/pharmacology* ; Cells, Cultured ; Fluorescent Antibody Technique ; Humans ; Microtubule-Associated Proteins/genetics ; Microtubule-Associated Proteins/metabolism* ; Myocytes, Cardiac/cytology ; Myocytes, Cardiac/metabolism* ; PTEN Phosphohydrolase/genetics ; PTEN Phosphohydrolase/metabolism* ; Phosphorylation ; Proto-Oncogene Proteins c-akt/antagonists & inhibitors* ; Proto-Oncogene Proteins c-akt/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; RNA, Messenger/genetics ; Rats ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Ribosomal Protein S6 Kinases, 70-kDa/genetics ; Ribosomal Protein S6 Kinases, 70-kDa/metabolism ; TOR Serine-Threonine Kinases/antagonists & inhibitors* ; TOR Serine-Threonine Kinases/genetics ; TOR Serine-Threonine Kinases/metabolism
C-reactive protein (CRP) is one of the most important biomarkers for arteriosclerosis and cardiovascular disease. Recent studies have shown that CRP affects cell cycle and inflammatory process in cardiac myocytes. Survivin is also involved in cardiac myocytes replication and apoptosis. Reduction of survivin expression is associated with less favorable cardiac remodeling in animal models. However, the effect of CRP on survivin expression and its cellular mechanism has not yet been studied. We demonstrated that treatment of CRP resulted in a significant decrease of survivin protein expression in a concentration-dependent manner in cardiac myocytes. The upstream signaling proteins of survivin, such as Akt, mTOR and p70S6K, were also downregulated by CRP treatment. In addition, CRP increased the protein and mRNA levels of PTEN. The siRNA transfection or specific inhibitor treatment for PTEN restored the CRP-induced downregulation of Akt/mTOR/p70S6K pathway and survivin protein expression. Moreover, pretreatment with a specific p53 inhibitor decreased the CRP-induced PTEN expression. ERK-specific inhibitor also blocked the p53 phosphorylation and PTEN expression induced by CRP. Our study provides a novel insight into CRP-induced downregulation of survivin protein expression in cardiac myocytes through mechanisms that involved in downregulation of Akt/mTOR/p70S6K pathway by expression of PTEN.
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1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Seok Min(강석민) ORCID logo https://orcid.org/0000-0001-9856-9227
Kim, Soo Hyuk(김수혁)
Park, Sung Ha(박성하) ORCID logo https://orcid.org/0000-0001-5362-478X
Oh, Jae Won(오재원) ORCID logo https://orcid.org/0000-0002-4585-1488
Lee, Beom Seob(이범섭)
Lee, Sang Hak(이상학) ORCID logo https://orcid.org/0000-0002-4535-3745
Jin, Tae Won(진태원)
Choi, Eun Young(최은영)
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