title: C-reactive protein inhibits survivin expression via Akt/mTOR pathway downregulation by PTEN expression in cardiac myocytes.
abstract: 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.
authors.affiliation: Graduate Program in Science for Aging, Yonsei University, Seoul, Republic of Korea; Cardiology Division, Severance Cardiovascular Hospital and Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea; Severance Integrative Research Institute for Cerebral and Cardiovascular Diseases (SIRIC), Yonsei University Health System, Seoul, Republic of Korea.
authors.forename: Beom Seob
authors.initials: BS
authors.lastname: Lee
authors.affiliation: Graduate Program in Science for Aging, Yonsei University, Seoul, Republic of Korea; Department of Applied Bioscience, College of Life Science, CHA University, Gyeonggi-do, Republic of Korea.
authors.forename: Soo Hyuk
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Cardiology Division, Severance Cardiovascular Hospital and Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jaewon
authors.initials: J
authors.lastname: Oh
authors.affiliation: Graduate Program in Science for Aging, Yonsei University, Seoul, Republic of Korea; Department of Applied Bioscience, College of Life Science, CHA University, Gyeonggi-do, Republic of Korea.
authors.forename: Taewon
authors.initials: T
authors.lastname: Jin
authors.affiliation: Graduate Program in Science for Aging, Yonsei University, Seoul, Republic of Korea; Department of Applied Bioscience, College of Life Science, CHA University, Gyeonggi-do, Republic of Korea.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Choi
authors.affiliation: Cardiology Division, Severance Cardiovascular Hospital and Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sungha
authors.initials: S
authors.lastname: Park
authors.affiliation: Cardiology Division, Severance Cardiovascular Hospital and Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sang-Hak
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Applied Bioscience, College of Life Science, CHA University, Gyeonggi-do, Republic of Korea.
authors.forename: Ji Hyung
authors.initials: JH
authors.lastname: Chung
authors.affiliation: Cardiology Division, Severance Cardiovascular Hospital and Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea; Severance Integrative Research Institute for Cerebral and Cardiovascular Diseases (SIRIC), Yonsei University Health System, Seoul, Republic of Korea; Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Seok-Min
authors.initials: SM
authors.lastname: Kang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002097:C-Reactive Protein / Q000494:pharmacology*; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics / Q000378:metabolism; D000077022:Survivin; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: C516989:Birc5 protein, rat; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D000077022:Survivin; D002097:C-Reactive Protein; C546845:mTOR protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase; C487216:Pten protein, rat