PMID- 18082048
OWN - NLM
STAT- MEDLINE
DCOM- 20080304
LR  - 20131121
IS  - 1008-8830 (Print)
IS  - 1008-8830 (Linking)
VI  - 9
IP  - 6
DP  - 2007 Dec
TI  - [Rapamycin affects eIF- 4E expression in rat myocardial fibroblasts infected by 
      Coxsackievirus B3].
PG  - 587-90
AB  - OBJECTIVE: This study examined the effect of rapamycin, an inhibitor of mammalian 
      target of rapamycin (mTOR), on eukaryotic initiation factor (eIF- 4E) expression 
      in rat myocardial fibroblasts infected by Coxsackievirus B3 (CVB3) in order to 
      identify the drug target for treatment of viral myocarditis. METHODS: Primary 
      cultured rat myocardial fibroblasts were treated with CVB3 with multiplicity of 
      infection (MOI=0.5 PFU/cell). The experiment consisted of four groups in which 
      the cultured rat fibroblasts cells were treated with CVB3, rapamycin (10 nM) and 
      CVB3 + rapamycin or placebo (control). Experimental model of CVB3-infected 
      myocardial fibroblasts was confirmed by detection of CVB3 mRNA expression with 
      RT-PCR and observation of morphological changes of the infected cells with 
      microscopy. eIF-4E expression was determined by both RT-PCR and Western Blot 
      methods. RESULTS: Morphological changes were found in the fibroblasts treated 
      with MOI 0.5 PFU/cell of CVB3 by transmission electron microscope and the viral 
      particles were found in the cytoplasm. CVB3 mRNA was expressed in CVB3-infected 
      fibroblasts after 1, 2, and 3 days after infection and 2 days after passage. The 
      gray scale values of the eIF- 4E /beta -actin in the control, the CVB3, the 
      rapamycin and the CVB3+rapamycin groups were 0.73 +/- 0.07, 0.87 +/- 0.03, 0.32 
      +/- 0.03 and 0.56 +/- 0.04 respectively detected by RT-PCR, and were 0.79 +/- 
      0.09, 1.35 +/- 0.12, 0.55 +/- 0.04, and 0.62 +/- 0.07 respectively detected by 
      Western blot. EIF- 4E expression in the CVB3 group was higher than that in the 
      control group. Both the rapamycin and the CVB3+rapamycin groups had lower eIF- 4E 
      expression than the control and the CVB3 groups. CONCLUSIONS: CVB3 can infect 
      myocardial fibroblasts and up-regulate the eIF- 4E expression in rat myocardial 
      fibroblasts. Rapamycin can inhibit eIF- 4E expression and may be a potential 
      medicine for treatment of viral myocarditis. It was suspected that mTOR/eIF- 4E 
      signal pathway in rat myocardial fibroblasts might play an important role in the 
      pathogenesis of viral myocarditis.
FAU - Chen, Chun-Yuan
AU  - Chen CY
AD  - Department of Pediatrics, Third Xiangya Hospital, Central South University, 
      Changsha 410013, China. ccyzdh@126.com
FAU - Sun, Yue-Nu
AU  - Sun YN
FAU - Yang, Zuo-Cheng
AU  - Yang ZC
FAU - Long, Yan-Qiong
AU  - Long YQ
LA  - chi
PT  - English Abstract
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Zhongguo Dang Dai Er Ke Za Zhi
JT  - Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics
JID - 100909956
RN  - 0 (Eukaryotic Initiation Factor-4E)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - *Enterovirus B, Human
MH  - Enterovirus Infections/*drug therapy/metabolism
MH  - Eukaryotic Initiation Factor-4E/*genetics
MH  - Fibroblasts/metabolism/virology
MH  - Gene Expression Regulation/*drug effects
MH  - Myocarditis/*drug therapy/etiology/metabolism
MH  - Myocardium/*metabolism
MH  - Rats
MH  - Sirolimus/*pharmacology/therapeutic use
EDAT- 2007/12/18 09:00
MHDA- 2008/03/05 09:00
CRDT- 2007/12/18 09:00
PHST- 2007/12/18 09:00 [pubmed]
PHST- 2008/03/05 09:00 [medline]
PHST- 2007/12/18 09:00 [entrez]
AID - 1008-8830(2007)06-0587-04 [pii]
PST - ppublish
SO  - Zhongguo Dang Dai Er Ke Za Zhi. 2007 Dec;9(6):587-90.